Basic Pharmacotherapy – Complete Full Notes
PST 06106
BASIC PHARMACOTHERAPY
Session 1: Introduction to Pharmacotherapy
Learning objectives
By the end of this session students are expected to be able to:
Define terminologies used in Pharmacotherapy
Describe principles and concepts applied in Pharmacotherapy
Explain importance of Pharmacotherapy in the management of common diseases
Definition of Common Terminologies used in Pharmacotherapy
Pharmacotherapy
is application of knowledge in making therapeutic decisions that are most likely to have maximum positive benefit for a specific patient.
Pharmacotherapy specialist:
is an individual who is specialized in administering and prescribing medication, and requires extensive academic knowledge in pharmacotherapy.
Pharmaceutical
personel
are experts in pharmacotherapy and are responsible for ensuring the safe, appropriate, and economical use of pharmaceutical drugs.
Definition of Common Terminologies used in Pharmacotherapy Cont.…..
Pathophysiology
is the physiology of abnormal states; specifically: the functional changes that accompany a particular syndrome or disease.
Also is the study of changes in the way the body works that result from disease or injury
Pharmaceutical care involves the process through which a pharmacist/ other pharmaceutical personnel cooperates with a patient and other professionals in designing, implementing, and monitoring a therapeutic plan that will produce specific therapeutic outcomes for the patient
Principles
and Concepts applied in pharmacotherapy
There
are
three
steps that are involved in the Pharmacotherapy process which are
;
Patient assessment
Development of the pharmacotherapy care plan
Evaluation of the impact or results of the care plan
Principles and Concepts applied in pharmacotherapy
Cont
…..
Fig 1.1 Patient Care Process in the Pharmacotherapy
Patient Assessment
The focus
is on drug therapy problems in which case it is important to assess if the patient’s problem(s) is/are be caused by drug therapy and can be managed by a change in drug therapy
The following is the list of drug therapy problems that should be identified;
Inappropriate drug
selection,
Need for additional drug therapy
Unnecessary drug therapy
Incorrect drug regimen
Therapeutic
duplication
Drug allergy/adverse drug event
Drug Interactions
Medication adherence issues
Patient Assessment
Cont
…..
Once a drug therapy problem is identified and categorized, it is then necessary to identify the cause of the problem, thereby leading to potential solutions.
The process of drug therapy problem identification is to assessing the patient’s drug therapy needs and ensuring appropriateness, effectiveness and safety of medications, and the patient’s adherence
Pharmacotherapy
Care Plan
The
pharmacotherapy care plan is important in order to achieve improved pharmacotherapy outcomes.
It
is the action plan developed from assessment of patient described
above.
Each
item in the patient’s problem list must be addressed in the care plan, and the care plan should be prioritized in the same way as the problem list.
The pharmacotherapy care plan has several key components for each
problem:
Current
drug regimen
Drug
therapy
problems
Therapy
goals, desired endpoints
Pharmacotherapy Care Plan
Cont
…
The
goals of therapy must be achievable and realistic for the
patien
Drug
therapy may aim to
cure a disease;
reduce or eliminate signs and/or symptoms
slow or halt the progression of a disease
prevent a disease
normalize laboratory values
and/or
assist in the diagnostic process
Therapeutic recommendations
Rationale
Therapeutic alternatives
Monitoring
Pharmacotherapy Care Plan
C
ont
…
Monitoring
helps in determining whether treatment goals and endpoints (achieving positive goals and avoiding negative endpoints) are being reached.
An effective monitoring plan must be realistic for the patient setting and include
specific monitoring parameters (clinical and laboratory/diagnostic test)
frequency of monitoring, and
When the patient needs to be seen again for follow-up.
Patient
education
Evaluation
The
patient care process involves continuous follow-up.
As
the pharmacotherapy care plan is implemented, the patient’s response to
therapy is
monitored, and changes in therapy may be necessary.
Changes in previous problems or the development of new signs and symptoms will require the assessment process and changes in the pharmacotherapy care plan
During the Pharmacotherapy process, it is important to consider/review the following factors for optimal therapeutic outcome
;
Evaluation
Cont
…….
Patient
Dermographics
—name, age, etc.
Chief Complaint—why the patient is seeking help, in the patient’s own words
History of Present Illness (HPI)—the patient’s story about why they are seeking help
Past Medical History (PMH)—including all significant illnesses, surgical procedures, injuries
Family History—age and health of immediate family (parents, siblings, children); for deceased relatives, the age and cause of death are included; any hereditary diseases should be noted
E
valuation
Cont
…….
Social
History—may include where the patient is from or lives, ethnicity/race, marital status, number of children, educational background, occupation, diet
Tobacco/Alcohol/Substance
Use
Allergy/Intolerances/Adverse
Drug Events (ADEs)—a common area where information from the patient is missing or
incomplete
Medication
History—should include current (or medications prior to admission if hospitalized) and previous medications; the list should include what the patient actually is taking, not just what is prescribed, and must include OTC drugs and dietary supplements (including herbal and complementary/alternative products
).
Evaluation
Cont
…….
Signs
and symptoms
Laboratory
and Other Diagnostic Tests
Diagnosis
.
Treatment
(Drug) plan
Follow-up plan
Activity: Small Group Discussion
What is the importance of Pharmacotherapy?
Importance of pharmacotherapy
Helps in optimization of drug treatment in complex pharmacotherapy patients such as;
Patients with multiple medications
Patients with multiple disease states or conditions
Patients on narrow therapeutic index medications
Patients on medications requiring laboratory monitoring
Helps in optimization of drug therapy in patients with high risk for loss of continuity of care such as;
Patients with multiple prescribers
Patients with recent transitions of care (e.g., hospital discharge, rehabilitation, skilled nursing facility discharge)
Importance of pharmacotherapy cont…
Helps in reduction of medication nonadherence especially in patients with;
Irregular refill history
History of failure to pick up new prescriptions
Stockpiling or incorrect pill counts
Financial burden (e.g., uninsured or underinsured)
Low health literacy
Patient’s beliefs indicate resistance to treatment
High-cost regimens
Noticeable decline in the health or functionality
Improves patients-pharmaceutical personnel relationship which is important for better therapeutic
outcome
Key Points
Pharmacotherapy
is the therapy that is provided using pharmaceutical
Pharmacotherapy comprises the safe, applicable, and cost-effective use of pharmaceutical drugs.
Steps that are involved in the Pharmacotherapy process which are Patient assessment, Development of the pharmacotherapy care plan and Evaluation of the impact or results of the care plan.
Pharmacotherapy helps in improving quality of patient care through optimal medication management based on sound
pharmacotherapeutic
principles.
Evaluation
What
is pharmacotherapy?
What are the steps involved in the pharmacotherapy process?
What is importance of pharmacotherapy?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic
Pharmacotherapy
Session 2: Therapeutic Drug Monitoring (TDM)
Learning Tasks
By the end of this session students are expected to be able to:
Define therapeutic drug monitoring
List principles and outline concepts of therapeutic drug monitoring
Outline criteria for therapeutic drug monitoring
List drugs that qualify for therapeutic drug
monotoring
Explain clinical significance of therapeutic drug monitoring
List limitations of therapeutic drug monitoring
Principles and Concepts of Therapeutic Drug Monitoring
Therapeutic
drug monitoring (TDM)
is defined as the use of drug concentration measurements in plasma as an aid to the management of drug therapy for the cure, alleviation or prevention of
disease. TDM
enables the assessment of the efficacy and safety of a particular medication in a variety of clinical settings
.
TDM aims at improving patient care by adjusting the dose of drugs for which clinical experience or clinical trial have shown it improved outcome in the general or special populations
Principles and Concepts of Therapeutic Drug Monitoring
Cont
…..
Therapeutic Drug Monitoring aims to individualize therapeutic regimens for optimal patient benefit and avoid both
sub therapeutic
and toxic plasma drug concentrations.
Specifically, TDM is a practice applied to a small group of drugs in which there is a direct relation between plasma drug concentration and pharmacological response
Therefore, close relationship between the plasma level of the drug and its clinical effect is essential.
If such a relationship does not exit TDM is of little value.
The measurement of plasma level is justified only when the information provided is of potential therapeutic benefit.
Principles and Concepts of Therapeutic Drug Monitoring
Cont.…..
In summary, TDM process involves the following;
Administration of a predetermined dose of drug
Collection of blood samples
Determination/measurements of blood samples using analytical procedures
Evaluation of Clinical effect of drug
Development/Adjustment
of dosage
regimen
Activity: Buzzing
What
are the criteria for therapeutic drug monitoring?
Criteria for therapeutic drug monitoring
The drug in question has a narrow therapeutic range,
eg
: Lithium, phenytoin, and digoxin
A direct relationship exists between the drug or drug metabolite levels in plasma and the pharmacological or toxic effects,
The therapeutic effect can not be readily assessed by the clinical observation,
Large individual variability in steady state plasma concentration exits at any given dose
Appropriate analytic techniques are available to determine the drug and metabolite
levels
Criteria for therapeutic drug
monitoring
Cont
…
Drugs for which relationship between dose and plasma concentration is unpredictable,
e.g
Phenytoin
Non compliance
Therapeutic failure
Major organ failure
Prevention of adverse drug effects
Drugs that qualify for therapeutic drug monitoring
Cardio
active drugs
amiodarone,
digoxin,
digitoxin
disopyramide
,
lignocaine,
procainamide,
propranolol and
quinidine
Drugs that qualify for therapeutic drug
monitoring Cont.….
Aminoglycoside
gentamycin,
A
mikacin
and tobramycin
Anti Cancer
methotrexate
Antidepressants
:
lithium
tricyclic
antidepressants
Drugs that qualify for therapeutic drug monitoring Cont.….
Antiepileptic
drugs
Phenytoin,
phenobarbitone
benzodiazepines,
carbamazepine,
Valproic
acid and
ethosuximide
Bronchodilators :
theophylline
Therapeutic drug monitoring process
Fig 2.1: Summary of TDM Process
Clinical significance of Therapeutic drug monitoring
…
Drug levels from TDM are used in conjunction with other clinical data to assist practitioners in determining how a patient is responding.
Drug levels provide a basis for individualizin
g
patient dosage regimens.
Drug levels assist in determining if a change in patient-specific
pharmacokinetics
has occurred during a course of treatment, whether as a result of a change in physiological state, a change in diet, or addition of other drugs.
Clinical significance of Therapeutic drug
monitoring Cont.
…
Maximizes drug efficacy
Helps in avoidance of drug toxicity
Identifies therapeutic failure due to
subtherapeutic
level
May help to identifies patients who are non compliant
Limitation of Therapeutic
D
rug
M
onitoring(TDM)
There may be some factors that may lead to incorrect interpretation of plasma drug levels such as;
Non-compliance of patient leading to low plasma drug levels
Low dose administered which leads to
subtharapapeutic
concentrations
Patient suffer from mal-absorption
Drug with low bioavailability may also lead to
subtherapeutic
concentrations
Concomitant drugs that could affect the plasma levels of the drug in question
Limitation of Therapeutic Drug Monitoring(TDM
) Cont.….
Hepatic or renal dysfunction
Diseases related to genetic factors affecting drug metabolism
.Time of administration of the drug is not accurate.
Dose administration error.
Inaccurate time of sampling, or timing was before steady-state is reached
Wrong site of sampling.
Lab assay error.
Limitation of Therapeutic Drug Monitoring(TDM) Cont.….
Effect of age
There is a great variability in response to drugs at extremes of age.
As an example, elderly patients are more sensitive to the CNS depressant effect of drugs but are less sensitive to cardiovascular effects of Propranolol.
It is well known that children are more sensitive to morphine.
Pregnancy
Many drugs can be affected by pregnancy state.
As an example, drug levels of phenytoin and
phenobarbitone
are lower during pregnancy
Key Points
TDM is a very important and widely used technique throughout the treatment process.
TDM is used when there is a sufficient relationship between the plasma level of the drug and its clinical effect
Evaluation
What is therapeutic drug monitoring?
What are steps involved during therapeutic drug monitoring?
What are criteria for therapeutic drug monitoring
What the clinical significance of therapeutic drug monitoring
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013), Pharmacotherapy Handbook (6th Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008): Pharmacotherapy: A Pathophysiologic Approach (7th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011) Principles & Practice Study Guide: A Case-Based Care Plan Approach: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009) Pharmacotherapy Casebook: A Patient-Focused Approach (7th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 3: Pharmacotherapy of Malaria
Learning Objectives
By the end of this session students are expected to be able to:
Define malaria
Explain pathophysiology of malaria
Explain the clinical presentation of malaria
Outline diagnosis of malaria
Describe pharmacological treatment of malaria
Describe monitoring malaria therapy
Activity: Buzzing
What is the disease status of a patient with malaria?
Definition of Malaria
Uncomplicated malaria
: defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction.
It has the following features; fever, headache, joint pains, malaise, vomiting, diarrhoea, body ache, body weakness, poor appetite, pallor, enlarged spleen
Severe malaria:
In a patient with P. falciparum asexual
parasitemia
and no other obvious cause of symptoms the presence of one or more of features listed below classify the patient as suffering from severe malaria
It has the following features; prostration/extreme weakness, impaired consciousness, change of behaviour, convulsions, respiratory distress (due to lactic acidosis and/or pulmonary oedema), bleeding tendency, jaundice, circulatory collapse, vomiting everything, inability to drink or breast feed
Pathophysiology of Malaria
The
Plasmodium species that infect humans are
P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi
(rarely).
The
basic elements of the life cycle are the same for all Plasmodium
sp
Transmission begins when a female Anopheles mosquito feeds on a person with malaria and ingests blood containing gametocytes.
During the following 1 to 2
wk
, gametocytes inside the mosquito reproduce sexually and produce infective
sporozoites
.
When
the mosquito feeds on another human,
sporozoites
are inoculated and quickly reach the liver and infect hepatocytes.
Pathophysiology of Malaria
cont
….
The parasites mature into tissue
schizonts
within hepatocytes. Each
schizont
produces 10,000 to 30,000
merozoites
, which are released into the bloodstream 1 to 3
wk
later when the hepatocyte ruptures.
Each
merozoite
can invade an RBC and there transform into a
trophozoite
Trophozoites
grow, and most develop into erythrocyte
schizonts
;
schizonts
produce further
merozoites
, which 48 to 72 h later rupture the RBC and are released in plasma.
Pathophysiology
of Malaria
cont.….
These
merozoites
then rapidly invade new RBCs, repeating the cycle
Some
trophozoites
develop into gametocytes, which are ingested by an
Anopheles
mosquito
They undergo sexual union in the gut of the mosquito, develop into oocysts, and release infective
sporozoites
, which migrate to the salivary glands
Plasmodium Life Cycle
Clinical Presentation Of Malaria
Signs and symptoms of uncomplicated Malaria
Fever
Headache
Malaise
Joint pains
Vomiting /diarrhoea
Body ache
Poor appetite
Body weakness
Pallor
Enlarged spleen
Signs
and symptoms of Severe Malaria
Extreme
weakness
Impaired consciousness
Change of behaviour ( hallucinations, delusions, agitation, and acute state of confusion)
Respiratory distress
Bleeding tendency
Jaundice
Circulatory collapse/ shock
Vomiting everything
Inability to drink or
breastfeed
Diagnosis of Malaria
Parasite-based diagnosis is recommended for all patients presenting with signs and symptoms of malaria.
The recommended investigations are: malaria microscopy and malaria rapid diagnostic tests (
mRDTs
)
In severe malaria, blood slide (BS) is a recommended malaria test as it quantifies parasitemia.
Activity: Small Group Discussion
What is pharmacological treatment of
malaria
?
Pharmacological Treatment of Malaria
Management OF Uncomplicated
M
alaria
Drug
of choice for treatment of uncomplicated malaria is Artemether-Lumefantrine (AL), which is a fixed formulation of artemether 20mg and lumefantrine 120mg or dispersible tablets for paediatric
use.
Dosage regimen of ALU
Pharmacological Treatment of Malaria Cont.…..
Use of
Artemether-lumefantrine
(
ALu
) in Pregnancy
Presently, Artemisinin compounds cannot be recommended for treatment of malaria in the first trimester of pregnancy.
In the first trimester of pregnancy quinine should be used as first line treatment.
After the first trimester
ALu
tablets is first line medicine.
Use of
Artemether-lumefantrine
(
ALu
) in Lactation
Due to the long elimination half-life of
Lumefantrine
(up to 10 days), it is not recommended in mothers breast-feeding children below 5kgs.
In this case quinine should be used
.
Pharmacological Treatment of Malaria Cont.…..
Management of Severe Malaria
Parenteral
artesunate
bwt
Major Anti Malarial Drugs
Monitoring Of Malaria Therapy
It is important to monitor Malaria therapy in order to evaluate if it is effective
Patients can be monitored clinically and/or by using laboratory test to confirm for absence/presence of malaria parasite in their blood
A follow-up period after the completion of the Malaria therapy varies according to the drugs used.
Follow-up periods longer than 14 days are appropriate for
amodiaquine
, chloroquine and SP which is 28 days
For
lumefantrine+artemether
is 42 days,
For
mefloquine
is 63 days
Monitoring Of Malaria Therapy
Cont
…
This allows drug levels in the blood to fall below the minimum therapeutic threshold.
Any recrudescence of parasites before this threshold is reached would be due to drug resistance
Recrudescence after this threshold is reached is not necessarily related to resistance (even sensitive parasites could recrudesce if blood drug levels are
subtherapeutic
).
Shorter follow-up (i.e. <14 days) will underestimate overall treatment failure rates
It is also important for patient to report any adverse reaction of the drugs that may occurs during Malaria therapy.
Key Points
P
. falciparum
causes microvascular obstruction and tissue ischemia, particularly in the brain, kidneys, lungs, and GI tract of nonimmune infants and adults; patients may die within days of their initial symptoms.
P.
vivax
, P.
ovale
, and
P.
malariae
typically do not compromise vital organs; mortality is rare.
Clinical
maanifestations
include recurrent fever and rigor, headache, myalgia, and nausea; hemolytic anemia and splenomegaly are common.
Treatment with antimalarial drugs is based on the species (if known) and drug resistance patterns in the area in which infection was acquired
Artemisinin
-based combination therapy (
eg
,
artemether
/lumefantrine) is the most rapidly active therapy and is available worldwide
Evaluation
What
is the disease status of a patient with Malaria?
What is the pathophysiology of malaria?
What is the diagnosis of malaria?
What parameters can be used to monitor malaria therapy
References
Wells BG,
DiPiro
J,
Schwinghammer
T (2013), Pharmacotherapy Handbook (6th Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008): Pharmacotherapy: A Pathophysiologic Approach (7th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011) Principles & Practice Study Guide: A Case-Based Care Plan Approach: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009) Pharmacotherapy Casebook: A Patient-Focused Approach (7th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 4: Pharmacotherapy of HIV/AIDS
Learning Objective
By the end of this session students are expected to be able to:
Define HIV/AIDS
Explain pathophysiology of HIV/AIDS
Explain the clinical presentation of HIV/AIDS
Outline diagnosis of HIV/AIDS
Describe pharmacological treatment of HIV/AIDS
Describe the monitoring of HIV/AIDS Therapy
Activity: Buzzing
What is HIV/AIDS?
INTRODUCTION
AIDs is a set of symptoms (or syndrome) caused by Human Immunodeficiency Virus (HIV). The clinical features may be due to HIV per se or as a result of immune system destruction.
It has the following features:
Fever, diarrhoea, weight loss, skin rashes, sores, generalized
pruritis
, altered mental status, persistent severe headache, oral thrush or Kaposi’s sarcoma may be found in patients with advanced disease
Most patients, however, present with symptoms due to opportunistic infections such as tuberculosis, candidiasis and pyogenic infections
Human immunodeficiency virus
Pathophysiology of HIV/AIDS
The virus through its envelope proteins attaches to the CD4 receptor and co-receptors found on the surface of T lymphocytes and macrophage to gain entry to the host cells.
Following entry of the HIV into a susceptible host cell using the enzyme reverse transcriptase, the viral genome copies itself from RNA to DNA genetic material.
The viral DNA copy enters the nucleus of the host cell and becomes intimately incorporated into the host cell’s own DNA using the enzyme integrase.
Pathophysiology of
HIV/AIDS CONT…
The virus thus becomes a permanent part of an infected person’s nuclear proteins.
There follows a latent period during which the provirus in the infected nucleus waits for an external stimulus to start reproducing.
CD4+ T lymphocytes, when stimulated by new HIV, other infections and infestations which would normally result in the CD4+ T lymphocyte reproducing itself, now responds to these stimuli by manufacturing HIV.
As more and more viruses are produced and leave the host cell, the cell membrane weakens leading eventually to the death of the infected CD4+ T lymphocytes
37
Pathophysiology of
HIV/AIDS CONT
…
The
multiple steps in replication of HIV provide multiple opportunities for intervention.
Therapeutic regimens may be directed at one or several of the following stages essential for viral replication:
Attachment of HIV to the host cell;
Reverse transcription of viral RNA to DNA;
Integration of the pro-viral DNA into the host cells’ DNA; or
Expression of the viral gene after it has been integrated into host cell DNA, including the transcription of more viral RNA and the translation of viral proteins
.
Clinical Presentation Of HIV/AIDS
In the absence of ART, disease progression goes through the following clinical
stages
Primary Infection or becoming HIV Infected
Most primary infection, i.e. new infection with HIV, usually is not immediately noticed.
It presents with short illnesses and flu-like symptoms such as fever, malaise, enlarged lymph nodes, sore throat, skin rash, and/or joint pain soon after being infected.
It may last for a few weeks.
This acute febrile illness is accompanied by widespread dissemination of the virus to different tissues, especially the lymphoid system. This is called
sero
-conversion illness.
Clinical Presentation Of HIV/AIDS
Cont
….
Clinically
Asymptomatic Stage
This stage is free of symptoms, except for the possibility of swollen glands: persistent generalized lymphadenopathy – Persistent Generalized Lymphadenopathy (PGL).
However, this is the stage where there is ongoing extensive immunologic fighting/changes and rapid viral replication begins.
This may last for an average of eight to ten years.
However, disease progression in children and elderly is faster due to high set point.
This is WHO Stage1
Clinical Presentation Of HIV/AIDS
Cont
…
Symptomatic HIV
Over time, the immune system loses the struggle to contain HIV, resulting in extensive destruction of CD4 cells
This is characterised by the occurrence of opportunistic infections (OIs), which is when) symptoms develop
The most common symptoms include fever, respiratory infections, cough, TB tuberculosis, weight loss, skin diseases, viral infections, oral thrush, pain, and lymphadenopathy
This is WHO Stage 2 or 3, depending on the particular OI
seen
Clinical Presentation Of HIV/AIDS
Cont
…
Acquired Immune Deficiency Syndrome (AIDS)
AIDS is defined as a point when a person with HIV develops severe immunosuppression, OIs, or malignancies/cancers.
Such conditions are: severe weight loss, Kaposi’s sarcoma, Cryptococcus meningitis, PCP, toxoplasmosis, CMV (Cytomegalovirus) retinitis, etc.
This is WHO Stage 4
Diagnosis of HIV/AIDS
ELISA Test
If an
ELISA test is positive, the Western blot test is usually administered to confirm the diagnosis. If an ELISA test is negative, but you think you may have HIV, you should be tested again in one to three months
ELISA is quite sensitive in chronic HIV infection, but because antibodies aren't produced immediately upon infection, you may test negative during a window of a few weeks to a few months after being infected.
Viral Load Test
bDNA
) and nucleic acid sequence-based amplification assay (NASBA). The basic principles of these tests are similar. HIV is detected using DNA sequences that bind specifically to those in the virus
Western Blot
Activity: Small Group Discussion
•What explanations can you give on monitoring therapy for HIV/AIDS?
Pharmacological treatment of HIV/AIDS
Early initiation of combination treatment (ART) is associated with health benefits in terms of reduced morbidity and mortality in all age groups.
In addition, ART is effective for preventing HIV transmission.
It also helps to drastically reduce TB incidences.
Therefore, all patients diagnosed with HIV should be initiated ART regardless of CD4 cell count and clinical stage
The most effective means to accomplish durable suppression of HIV replication is the simultaneous initiation of combinations of effective anti HIV drugs with which the patient has not been previously treated and that are not cross resistant with antiretroviral agents with which the patient has been treated previously
Each of the antiretroviral drugs used in combination therapy regimens should always be used according to optimum schedules and dosages
Antiretroviral Agents
The
recommended antiretroviral drugs to be used fall into the following main categories:
Nucleotide reverse transcriptase inhibitors (NRTIs)
Nucleoside reverse transcriptase inhibitors (NRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Protease inhibitors (
Pls
)
Integrase strand transfer inhibitors (INSTI)/ Integrase inhibitors
Fusion inhibitors
Chemokine receptor inhibitors/CCR5 inhibitors
First Line ART
Triple therapy consisting of 2 NRTI + 1 NNRTI
Pharmacological treatment of
HIV/AIDS Cont..
NOTE:
Clients on TDF/3TC/EFV600 can be switched to TDF/3TC/ EFV400 (when available) to reduce CNS related toxicity with exception of Pregnant women and TB-HIV Co-infected patients
TDF 300mg based regimens should not be initiated on patients with weight less than 35kg.
EFV400 based regimens should not be initiated on patients with weight below 20Kg
Pharmacological treatment of HIV/AIDS Cont..
Second-line Antiretroviral Therapy in Adults and Adolescents
Treatment failure will be based on
virological
Drugs used as the second line in Tanzania include
Pharmacological treatment of
HIV/AIDS Cont..
NRTIs/
NtRIs
Zidovudine (AZT)
Tenofovir
(TDF)
Abacavir
(ABC)
Lamivudine (3TC)
Emtricitabine
(FTC)
PIs
Atazanavir
boosted by Ritonavir (ATV/r)
Lopinavir
boosted by Ritonavir (LPV/r)
INSTIs
Dolutegravir
(DTG
)
Pharmacological treatment of HIV/AIDS Cont..
The second line NRTI choice for adults and adolescents depends on the first line regimen
For patients on TDF based regimens in first line, the preferred second line option is AZT plus 3TC combined with a ritonavir-boosted PI, preferably ATV/r because it is dosed once daily and has fewer metabolic complications and side
effects
Pharmacological treatment of HIV/AIDS Cont..
Third-Line Art Treatment
Patients failing 2nd line regimens may have extensive NRTI and NNRTIs associated resistance mutations (RAMS) which preclude/minimise their use in third-line regimens.
Therefore, 3rd line regimens, in order to have at least two or preferably three effective drugs, need to be constructed using other new classes of drugs or second generation formulations of previous drugs
These second generation drugs usually have a higher genetic barrier to resistance and their efficacy is not compromised by RAMs associated with the first generation formulations. Therefore, the following are used:
Pharmacological treatment of HIV/AIDS Cont..
Integrase Inhibitors:
Dolutegravir
50mg (DTG) and
Raltegravir
400mg (RAL),
Second generation PIs:
Darunavir
800mg /Ritonavir 100mg (DRV/r)
Second generation NNRTI:
Etravirine
200g (ETV
Monitoring Of Antiretroviral Therapy
Tests for Monitoring responses to Antiretroviral treatment and diagnosis of treatment failure/toxicity are important
Clinical assessment and laboratory tests play a key role in assessing individuals before ART is initiated, monitoring treatment response and possible toxicity of ARV drugs.
The following laboratory tests are recommended:
HIV Viral Load test is a preferred monitoring approach to diagnose and confirm early treatment failure.
HVL for adults and adolescents should be done 6 months after initiation of ART
Successful antiretroviral therapy result in decrease of HIV viral load, immune recovery and therefore increase in number of CD4 cells
.
Monitoring Of Antiretroviral Therapy
Cont
…
CD4 T lymphocytes count should also be done at baseline for all clients.
CD4 cells progressively decrease as HIV advances and immune status deteriorates. Measurements of CD4 cells counts are important immunological markers of the disease progression.
CD4 cells counts are reported in percentage (%).
CD4 testing will be measured as a baseline test and for suspected treatment failure for those clients on ART
Monitoring of cd4 count
Monitoring Of Antiretroviral Therapy
Cont
…
A complete blood count (If not available, conduct hemoglobin test for patients on AZT based regimens)
Urinalysis to exclude proteinuria (HIV associated nephropathy or HIVAN) and glycosuria (Diabetes Mellitus).
Tests to rule out active TB (sputum AFB,
GeneXpert
, CXR) in cases where there is suspected TB from the screening tool
Urine pregnancy test (to women of reproductive age) in order to identify PLHIV requiring EFV 600mg.
Liver function tests (serum alanine aminotransferase, ALT) if on anti-TB drugs or requiring NVP based treatment
Renal function tests (serum creatinine, blood urea nitrogen (BUN)) for patients requiring TDF based regimens
Lipids test (for clients requiring PIs)
Key Points
HIV/AIDs
is a set of symptoms (or syndrome) caused by Human Immunodeficiency Virus (HIV)
HIV is commonly transmitted via unprotected sexual activity,
blood
transfusions, hypodermic needles, and from mother to child.
Upon acquisition of the virus, the virus replicates inside and kills T helper cells, which are required for almost all adaptive immune responses.
Diagnosis of HIV/AIDS is commonly done by ELISA, Viral load and Western blot tests
Treatment of HIV/AIDS is initiated
regarless
of CD4 count
Varieties of tests are done in order to monitor ART therapy
Evaluation
What
is the disease status of a patient with HIV/AIDS?
What is the pathophysiology of HIV/AIDS?
What is the diagnosis of HIV/AIDS?
What are the first line treatment regimes for HIV/AIDS?
What laboratory tests are used to monitor ART?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
BASIC PHARMACOTHERAPY
Pharmacotherapy of Tuberculosis
Complete learning session
1 / 20
Basic Pharmacotherapy
Learning outcomes
2 / 20
Basic Pharmacotherapy
Why this topic matters
3 / 20
Basic Pharmacotherapy
Core definition
4 / 20
Basic Pharmacotherapy
Foundational principles
5 / 20
Basic Pharmacotherapy
Key components
6 / 20
Basic Pharmacotherapy
Classification and organisation
7 / 20
Basic Pharmacotherapy
How the process works
8 / 20
Basic Pharmacotherapy
Professional terminology
9 / 20
Basic Pharmacotherapy
Practical application
10 / 20
Basic Pharmacotherapy
Quality requirements
11 / 20
Basic Pharmacotherapy
Safety and risk control
12 / 20
Basic Pharmacotherapy
Common errors
13 / 20
Basic Pharmacotherapy
Preventing avoidable mistakes
14 / 20
Basic Pharmacotherapy
Worked application
15 / 20
Basic Pharmacotherapy
Practice scenario
16 / 20
Basic Pharmacotherapy
Decision points
17 / 20
Basic Pharmacotherapy
Connection to patient care
18 / 20
Basic Pharmacotherapy
Session summary
19 / 20
Basic Pharmacotherapy
Self-check questions
20 / 20
PST 06106
Basic Pharmacotherapy
Session 6: Pharmacotherapy of Leprosy
11/11/2020
Pharmacotherapy of Leprosy
Learning Task
By the end of this session students are expected to be able to:
Define leprosy
Explain pathophysiology of leprosy
Explain the clinical presentation of leprosy
Outline diagnosis of leprosy
Describe pharmacological treatment of leprosy
Describe monitoring of leprosy therapy
11/11/2020
Pharmacotherapy of Leprosy
Activity: Small Group Discussion
•
What
is the first line treatment of Pneumonia?
Definition of Leprosy
Leprosy is a chronic infectious disease caused by
Mycobacterium
leprae
(M.
leprae
).
It mainly affects the
skin, peripheral nerves, and mucous membranes.
It is a disease mainly of human beings, which affects
people of all races, all ages, and both sexes.
Similar to TB, leprosy bacilli are mainly transmitted through
infectious droplets that are spread by an infectious individual through coughing and sneezing.
11/11/2020
Pharmacotherapy of Leprosy
Definition
of Leprosy
Cont.…
Patients
carrying many leprosy bacilli are called multibacillary (MB) patients. They are the main source of infection.
People may carry the bacilli but not develop the disease.
These people, called healthy carriers, are also probably able to transmit the bacilli to others.
Individuals with few bacilli in their body are called paucibacillary (PB).
Like healthy carriers, they are not a significant source of infection
11/11/2020
Pharmacotherapy of Leprosy
Pathophysiology of Leprosy
Onset of leprosy is insidious.
The disease affects nerves, skin and eyes.
It may also affect mucosa (mouth, nose, pharynx), testes, kidney, voluntary/smooth muscles,
reticulo
-endothelial system, and vascular endothelium.
Bacilli enter the body usually through respiratory system.
It has low
pathogenicity,
only a small proportion of infected people develop signs of the disease.
Though infected, majority of the population do not develop the disease.
11/11/2020
Pharmacotherapy of Leprosy
Pathophysiology of
Leprosy Cont.…..
After entering the body, bacilli migrate towards the neural tissue and enter the Schwann cells. Bacteria can also be found in, macrophages, muscle cells and endothelial cells of blood vessels. After entering the Schwann cells /macrophage; fate of the bacterium depends on the resistance of the infected individual towards the infecting organism.
Bacilli start multiplying slowly (about 12-14 days for one bacterium to divide into two) within the cells, get liberated from the destroyed cells and enter other unaffected cells.
Till this stage person remains free from signs and symptoms of leprosy
.
11/11/2020
Pharmacotherapy of Leprosy
Pathophysiology of
Leprosy Cont
.…..
As the bacilli multiply, bacterial load increases in the body and infection is recognized by the immunological system.
Lymphocytes and
histiocytes
(macrophages) invade the infected tissue.
At this stage clinical manifestation may appear as involvement of nerves with impairment of sensation &/ or skin patch.
If it is not diagnosed and treated in the early stages, further progress of the diseases is determined by the strength of the patient’s immune response
11/11/2020
Pharmacotherapy of Leprosy
Pathophysiology of Leprosy Cont.…..
Specific and effective cell mediated immunity (CMI) provides protection to a person against leprosy.
When specific CMI is effective in eliminating/ controlling the infection in the body, lesions heal spontaneously or it produces
pauci
-bacillary (PB) type of leprosy.
If CMI is deficient; the disease spreads uncontrolled and produces multi bacillary (MB) leprosy with multiple system involvement.
Some times, the immune response is abruptly altered, either following multiple drug treatment (MDT) or due to improvement of immunological status, which results in – 12 – the inflammation of skin or / and nerves and even others tissue, called as leprosy reaction
11/11/2020
Pharmacotherapy of Leprosy
Clinical presentation and Diagnosis of Leprosy
The diagnosis of leprosy
The diagnosis of leprosy relies on both passive and active case-finding.
Clinical diagnosis.
This is achieved through observation of signs or symptoms of leprosy which includes;
One or more pale or reddish, hypo-pigmented patch(
es
) on the skin with diminished or loss of sensation.
Painless swelling or lumps in the face and/or earlobes.
Enlarged and/or tender nerves.
11/11/2020
Pharmacotherapy of Leprosy
Clinical presentation
Cont.….
Burning sensation of the skin.
Numbness or tingling of hands and/or feet.
Weakness of eyelids, hands, and/or feet.
Painless wounds or burns on the hands and/or feet.
11/11/2020
Pharmacotherapy of Leprosy
Clinical presentation and Diagnosis of
Leprosy Cont.…
Examination of other organs
:
Leprosy can affect a few organs other than skin and peripheral nerves.
Depending on the duration of the disease and the spread of leprosy through the body, various other organs may show signs typical for leprosy
11/11/2020
Pharmacotherapy of Leprosy
Activity: Small Group Discussion
•
What
is the first line treatment of Leprosy??
Pharmacological Treatment Of Leprosy
Treatment regimens
The drugs and dosages for PB and MB for both adults and children are shown below
:
Adults (MB)
Monthly treatment: Day 1
Clofazimine
Dapsone
100
mg
11/11/2020
Pharmacotherapy of Leprosy
Pharmacological Treatment Of
Leprosy Cont.….
Daily treatment: Days 2–28
Clofazimine
Dapsone
Duration of treatment
12 blister packs to be taken within a period of 12-18 months
11/11/2020
Pharmacotherapy of Leprosy
Pharmacological Treatment Of
Leprosy
Cont
…
Children 10-14 years (MB)
Monthly treatment: Day 1
Clofazimine
Dapsone
Daily treatment: Days 2–28
Clofazimine
Dapsone
Duration of treatment
12 blister packs to be taken within a period of 12-18 months
11/11/2020
Pharmacotherapy of Leprosy
Pharmacological Treatment Of Leprosy
Cont
…
Adults (PB)
Monthly treatment: Day 1
Dapsone
Daily treatment: Days 2–28
Dapsone
Duration of treatment
Six blister packs
to be taken within a period of 6–9 months.
11/11/2020
Pharmacotherapy of Leprosy
Pharmacological Treatment Of Leprosy
Cont
…
Children 10-14 years (PB)
Monthly treatment: Day 1
Dapsone
Daily Treatment: Days 2–28
Dapsone
Duration of treatment
Six blister packs to be taken within a period of 6–9 months.
Note:
Adjust the dose appropriately for a child (PB) younger than 10 years. For example,
dapsone
11/11/2020
Pharmacotherapy of Leprosy
11/11/2020
Pharmacotherapy of Leprosy
Monitoring of Leprosy Therapy
Treatment monitoring
Multi Drug Therapy
(MDT)
should be provided to the patient as close to the patient’s home as possible
Based
on
the geographic distribution of health facilities, the availability of trained staff, and the patient’s wish, the health worker and/or
District Tuberculosis and Leprosy Coordinator(DTLC)
decides where
Multi Drug Therapy
should be delivered. In principle, every health facility should be able to provide MDT
Staff need to be trained on leprosy management as described in the
National Tuberculosis and Leprosy Programme(NTLP)
training
manual for
health workers
11/11/2020
Pharmacotherapy of Leprosy
Monitoring of Leprosy
Therapy Cont.…
Patients should have access to treatment on any day immediately after finishing the blister pack, but they should be given an appointment to attend a fixed clinic day in order to be reviewed and assessed by a trained health worker or DTLC
The trained health worker or DTLC should arrange leprosy clinics every three months
The DTLC, in collaboration with the district pharmacist, is responsible for the supply of MDT drugs and drugs for treating reactions
11/11/2020
Pharmacotherapy of Leprosy
Monitoring of Leprosy Therapy Cont.…
There should always be a minimum of three blister packs in stock for every patient attending the clinic at any given time
Under normal circumstances patients should not be given more than a one-month drug supply (one blister pack)
Those patients who cannot come on monthly basis to a health facility due to problems such as long distance, impassable roads during the rainy season, nomadic lifestyle, etc., may be given drugs for more than one month, sufficient to cover the expected period of absence
Under exceptional circumstances, a full course supply can be
given
11/11/2020
Pharmacotherapy of Leprosy
Monitoring of Leprosy Therapy Cont.…
When patients are given more than a one-month supply, it is better to involve a formal or informal community leader or relative who will then be oriented to support the patient to complete the full course of treatment (accompanied MDT
Each
time a patient comes to a health facility to collect an MDT blister pack, a health worker should ask the patient about new complaints regarding nerve function impairment.
If there are any complaints, the health worker should conduct nerve function tests to assess for
damage
11/11/2020
Pharmacotherapy of Leprosy
Monitoring of Leprosy Therapy Cont.…
If there are indications of nerve damage, the patient should be managed appropriately
In case of uncertainty, the health worker should refer the patient to the DTLC
The health staff is also responsible for tracing a patient who does not attend for two consecutive months
When the patient is found, she/he should be persuaded to continue with treatment
11/11/2020
Pharmacotherapy of Leprosy
Key Points
Leprosy
is caused by a slow-growing type of bacteria called Mycobacterium
leprae
(M.
leprae
)
The disease mainly affects the skin, the peripheral nerves, mucosal surfaces of the upper respiratory tract and the eyes.
The main symptom of leprosy is disfiguring skin sores, lumps, or bumps that do not go away after several weeks or months. The skin sores are pale-colored.
The disease was transmitted by contact between cases of leprosy and healthy persons.
Leprosy is curable with a combination of drugs known as multidrug therapy (MDT)
11/11/2020
Pharmacotherapy of Leprosy
Evaluation
What
is Leprosy?
What are the signs and symptoms of Leprosy?
What is the pathophysiology of Leprosy?
What is the treatment of leprosy?
11/11/2020
Pharmacotherapy of Leprosy
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz
M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY:
McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill
.
11/11/2020
Pharmacotherapy of Leprosy
End
11/11/2020
Pharmacotherapy of Leprosy
PST 06106
Basic Pharmacotherapy
Session 7: Pharmacotherapy of Pharyngitis, Sinusitis, and Otitis Media
Learning objectives
By the end of this session students are expected to be able to:
Define pharyngitis, sinusitis, and otitis media
Explain pathophysiology of pharyngitis, sinusitis, and otitis media
Explain the clinical presentation of pharyngitis, sinusitis, and otitis media
Outline diagnosis of pharyngitis, sinusitis, and otitis media
Describe pharmacological treatment of pharyngitis, sinusitis, and otitis media
Describe monitoring of pharyngitis, sinusitis, and otitis media therapy
Activity: Buzzing
•
What
is pharyngitis??
Definition of Pharyngitis, Sinusitis, and Otitis Media
Pharyngitis
is an acute infection of the oropharynx or nasopharynx.
It is caused by virus and bacteria
Viruses cause the majority of acute pharyngitis cases
Specific etiologies include rhinovirus, coronavirus, adenovirus, herpes simplex virus, influenza virus, parainfluenza virus, and Epstein-Barr virus
Group A
β
–hemolytic streptococci (GAS; also known as
S.
pyogenes
),
is the
primary
bacterial
cause.
Other, less-common causes of acute pharyngitis are groups C and G
Streptococcus, Corynebacterium
diphtheriae
, Neisseria gonorrhoeae, Mycoplasma pneumoniae,
Arcanobacterium
haemolyticum
, Yersinia
enterocolitica
, and Chlamydia pneumonia
Pathophysiology Of Pharyngitis
The mechanism by which
Group A beta haemolytic streptococci (GAS)
causes pharyngitis is not well defined
Asymptomatic pharyngeal carriers of the organism may have an alteration in host immunity (e.g., a breach in the pharyngeal mucosa) and the bacteria of the oropharynx, allowing colonization to become an infection
Pathogenic factors associated with the organism itself may also play a role
These include pyrogenic toxins,
hemolysins
, streptokinase, and
proteinase.
Clinical presentation and Diagnosis of Pharyngitis
General
A sore throat of sudden onset that is mostly self-limited
Fever and constitutional symptoms resolving in about 3 to 5 days
Clinical signs and symptoms are similar for viral causes and
nonstreptococcal
bacterial
causes
Clinical presentation and Diagnosis of
Pharyngitis
Cont
…
Signs and Symptoms
Sore throat ( pain or irritation in the throat that occurs with/without swallowing)
Pain on swallowing
Fever
Headache, nausea, vomiting, and abdominal pain (especially children)
Erythema/inflammation of the tonsils and pharynx with or without patchy exudates
Enlarged, tender lymph nodes
Red swollen uvula,
petechiae
on the soft palate, and a
scarlatiniform
rash
Several symptoms that are not suggestive of group A streptococci are cough, conjunctivitis,
coryza
, and diarrhea
Clinical presentation and Diagnosis of Pharyngitis
Cont
…
Signs Suggestive of Viral Origin for Pharyngitis
Conjunctivitis
Coryza (irritation and swelling of the mucous membrane in the nose)
Cough
Diarrhea
Laboratory Tests
Throat swab and culture
Rapid antigen detection testing (RADT)
Activity: Small Group Discussion
What
is the first line treatment of
Pharyngitis ?
Pharmacological treatment of Pharyngitis
The goals of treatment for pharyngitis are to;
Improve clinical signs and symptoms,
M
inimize
adverse drug reactions,
Prevent
transmission to close contacts, and
P
revent
acute rheumatic fever and suppurative complications, such as
peritonsillar
abscess, cervical lymphadenitis, and
mastoiditis
Pharmacological treatment of Pharyngitis
For recurrent
pharyngitis
Monitoring of Pharyngitis Therapy
Most pharyngitis cases are self-limited; however, antibiotics hasten resolution when given early for proven cases of
Group A beta hemolytic streptococci (GAS) pharyngitis
.
Generally, fever and other symptoms resolve within 3 or 4 days of onset without antibiotics; however, symptoms will improve 16 hours to 2 days earlier with antibiotic therapy.
Follow-up testing is generally not necessary for index cases or in asymptomatic contacts of the index patient.
However, for patients who remain symptomatic or when symptoms recur despite completion of treatment, posttreatment throat cultures 2 to 7 days after completion of antibiotics should be done
.
Key Points
Acute
pharyngitis is characterized by the rapid onset of sore throat and pharyngeal inflammation (with or without exudate). .
It can be caused by a variety of viral and bacterial pathogens, including group A Streptococcus (GAS),
Diagnosis can be done clinically especially and by using lab test
Most of the time the condition is self limiting, but antibiotics may be needed
Evaluation
What
is pharyngitis?
What are the signs and symptoms of pharyngitis?
How is pharyngitis diagnosed?
How is the treatment of pharyngitis
REFER Students to Handout 7.1: Pharmacotherapy of
Sinusitis
REFER Students to Handout 7.2: Pharmacotherapy of Otitis Media
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 8: Pharmacotherapy of Pneumonia
Learning objectives
By the end of this session students are expected to be able to:
Define pneumonia
Explain pathophysiology of pneumonia
Explain the clinical presentation of bronchitis and pneumonia
Outline diagnosis of bronchitis and pneumonia
Describe pharmacological treatment of bronchitis and pneumonia
Describe monitoring of bronchitis and pneumonia therapy
Activity: Buzzing
•
What
is Pneumonia?
Definition of Pneumonia
Pneumonia
Pneumonia is the inflammation of the lung tissue.
Pneumonia can either be primary (to the causing organism) or secondary to pathological damage in the respiratory system
It occurs in persons of all ages, although the clinical manifestations are most severe in the very young, the elderly, and the chronically ill
.
The most prominent pathogen causing community-acquired pneumonia (CAP) in otherwise healthy adults is S. pneumonia and accounts for up to 75% of all acute cases.
Other common pathogens include M.
pneumoniae
, Legionella species, C.
pneumoniae
, H.
influenzae
, and a variety of viruses including influenza.
Pathophysiology of Pneumonia
Microorganisms gain access to the lower respiratory tract by three routes.
Through inhalation as aerosolized particles, or
via the bloodstream from an
extra pulmonary
site of infection;
Aspiration of oropharyngeal contents which is a common occurrence in both healthy and ill persons during sleep is the major mechanism by which pulmonary pathogens gain access to the normally sterile lower airways and alveoli.
Pathophysiology of Pneumonia CONT…..
When pulmonary defense mechanisms are functioning optimally, aspirated microorganisms are cleared from the region before infection can become established;
However, aspiration of potential pathogens from the oropharynx can result in pneumonia if lung defenses are impaired
Factors that promote aspiration, such as altered sensorium and neuromuscular disease, may result in an increase in the size of the inoculum delivered to the lower respiratory tract, thereby overwhelming local defense mechanisms.
Pathophysiology of Pneumonia CONT…..
Lung
infections with viruses suppress the antibacterial activity of the lung by impairing alveolar macrophage function and mucociliary clearance, thus setting the stage for secondary bacterial pneumonia.
Mucociliary transport is also depressed by ethanol and narcotics and by obstruction of a bronchus by mucus, tumor, or extrinsic compression.
All these factors can severely impair pulmonary clearance of aspirated bacteria hence causing infection in the
lung.
Clinical Presentation And Diagnosis Of Pneumonia
Signs and symptoms
Abrupt onset of fever, chills, dyspnea, and productive cough
Rust-colored sputum or hemoptysis
Pleuritic chest
pain
Clinical Presentation And Diagnosis Of Pneumonia CONT…
Physical examination
Tachypnea and tachycardia
Dullness to percussion
Increased tactile fremitus, whisper
pectoriloquy
, and
egophony
Chest wall retractions and grunting respirations
Diminished breath sounds over affected area
Inspiratory crackles during lung expansion
Clinical Presentation And Diagnosis Of Pneumonia CONT…
Chest radiograph
Dense lobar or segmental infiltrate
Laboratory tests
Leukocytosis with predominance of
polymorphonuclear
cells
Low oxygen saturation on arterial blood gas or pulse oximetry
Sign and symptoms of pneumonia
Activity: Small Group Discussion
What is the first line treatment of Pneumonia?
Pharmacological Treatment Of Pneumonia
Treatment goals of pneumonia includes:
Eradication of the offending organism through selection of the appropriate antibiotic and complete clinical cure
Most cases of viral pneumonia are self-limiting, although therapy of influenza pneumonia with specific antiviral agents (oseltamivir and
zanamivir
) may hasten recovery
.
Treatment of Pneumonia in Adults
First- line
Treatment of Atypical Community Acquired Pneumonias
Pharmacological Treatment Of Pneumonia In Children
Non-severe pneumonia
OR B:
Give the first dose at the clinic and teach the mother how to give the other doses at home.
And
Encourage breasting and feeding.
Pharmacological Treatment Of Pneumonia In Children
Severe Pneumonia
OR
A:
AND
then, If child responds well, complete treatment at home or in hospital with
Pharmacological Treatment Of Pneumonia In Children
Cont
…..
Very severe Pneumonia:
A:
AND
A
:
A
:
Alternatively,
A:
Monitoring Of Pneumonia Therapy
After therapy has been instituted, appropriate clinical parameters such as signs and symptoms and other laboratory markers should be monitored to ensure the efficacy and safety of the therapeutic regimen.
For patients with CAP or pneumonia from any source of mild to moderate clinical severity, the time to resolution of cough, decreasing sputum production, and fever, as well as other constitutional symptoms of malaise, nausea, vomiting, and lethargy, should be noted.
Monitoring Of Pneumonia Therapy Cont.….
Initial resolution should be observed within the first 2 days and progression to complete resolution within 5 to 7 days but usually no more than 10 days.
For patients with HAP, substantial underlying diseases, or both, additional parameters can be followed, including the magnitude and character of the peripheral blood WBC count, chest radiograph, and blood gas determinations.
Monitoring Of Pneumonia Therapy cont.
…
.
Similar to patients with less severe disease, some resolution of symptoms should be observed within 2 days of instituting antibiotic therapy.
If no resolution of symptoms is observed within 2 days of starting seemingly appropriate
antibiotic therapy or if the patient’s clinical status is deteriorating, the appropriateness of initial antibiotic therapy should be critically reassessed.
The patient should be evaluated carefully for deterioration of underlying concurrent disease(s).
Monitoring Of Pneumonia Therapy cont
.….
Additionally, the caregiver should consider the possibility of changing the initial antibiotic therapy to expand antimicrobial coverage not included in the original regimen (e.g.
Mycoplasma, Legionella,
and anaerobes).
Furthermore, the need for antifungal therapy (lipid-based amphotericin B) should be considered.
Some resolution of symptoms should be observed within 2 days of starting proper antibiotic therapy, with complete resolution expected within 10 to 14 days
Key Points
Pneumonia
is an infection of the lung tissue whereby the air sacs in the lungs become infected with microorganisms, fluid and inflammatory cells and hence they lungs fail to work properly.
Diagnosis of pneumonia is based on symptoms and signs of an acute lower respiratory tract infection, and can be confirmed by a chest X-ray showing new shadowing that is not due to any other cause
Penicillins as well as other antibiotics can be used for treatment of Pneumonia as indicated
Evaluation
What
is pneumonia?
What are the signs and symptoms of pneumonia?
How is pneumonia diagnosed?
How is the treatment of pneumonia in adult and children?
Which clinical parameters can be used to monitor pneumonia therapy?
REFER Students to
Handout 8.1:
Classification of Pneumonia and Risk Factors
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 9: Pharmacotherapy of Bronchitis
12/3/2020
Pharmacotherapy of Leprosy
Learning objectives
By the end of this session, you are expected to be able to:
Define bronchitis
Explain pathophysiology of bronchitis
Explain the clinical presentation of bronchitis
Outline diagnosis of bronchitis
Describe pharmacological treatment of bronchitis
Describe the monitoring of bronchitis
therapy
Activity: Buzzing
•What
is Chronic Bronchitis??
Definition of Bronchitis
Bronchitis is an infection resulting from the inflammation of the lining of the lungs/bronchioles
It is subdivided into two types
Acute
Bronchitis
Chronic Bronchitis
Acute bronchitis
is one of the most common conditions associated with antibiotic misuse.
Respiratory viruses are by far the most common infectious agents associated with acute
bronchitis
Chronic bronchitis
It defined by a chronic productive cough for three months in each of two successive years in a patient in whom other causes of chronic cough have been excluded.
Chronic Bronchitis
It defined by a chronic productive cough for three months in each of two successive years in a patient in whom other causes of chronic cough have been excluded.
Patients may get secondary bacterial infection with development of fever and production of thick smelly sputum.
The disease is a result of several contributing factors; the most prominent include;
cigarette smoking,
exposure to occupational dusts, fumes, and environmental pollution; and
Host factors [e.g., genetic factors and bacterial (and possibly viral) infections
].
Pathophysiology of Chronic Bronchitis
Microorganisms gain access to the lower respiratory tract by three routes.
Through inhalation as aerosolized particles, or
via the bloodstream from an
extra pulmonary
site of infection;
Aspiration of oropharyngeal contents which is a common occurrence in both healthy and ill persons during sleep is the major mechanism by which pulmonary pathogens gain access to the normally sterile lower airways and alveoli.
When pulmonary defense mechanisms are functioning optimally, aspirated microorganisms are cleared from the region before infection can become established;
However, aspiration of potential pathogens from the oropharynx can result in pneumonia if lung defenses are impaired
Pathophysiology of Chronic
Bronchitis Cont..
Factors that promote aspiration, such as altered sensorium and neuromuscular disease, may result in an increase in the size of the inoculum delivered to the lower respiratory tract, thereby overwhelming local defense mechanisms.
Lung infections with viruses suppress the antibacterial activity of the lung by impairing alveolar macrophage function and mucociliary clearance, thus setting the stage for secondary bacterial pneumonia.
Mucociliary transport is also depressed by ethanol and narcotics and by obstruction of a bronchus by mucus, tumor, or extrinsic compression.
All these factors can severely impair pulmonary clearance of aspirated bacteria hence causing infection in the lung
Clinical Presentation And Diagnosis Of Chronic Bronchitis
Signs and symptoms
Excessive sputum expectoration
Cyanosis (advanced disease)
Obesity
Clinical Presentation And Diagnosis Of Chronic
Bronchitis
Cont
….
Physical examination
Chest auscultation usually reveals inspiratory and expiratory rates,
Rhonchi(Sound generated by the movement of air through the respiratory system), and mild wheezing with an expiratory phase that is frequently prolonged;
H
yper resonance
on percussion(Too much air present within the lung) with obliteration of the area of cardiac dullness(dense tissue)
Normal vesicular breathing sounds are diminished
Clubbing of digits (advanced disease)—- enlargement of the tip of the lung and change in angle, present in bronchitis but not in asthma and pneumonia
Clinical Presentation And Diagnosis Of Chronic Bronchitis
Cont
….
Chest radiograph
Increase in anteroposterior diameter of the thoracic cage (observed as a barrel chest
)—rib cage broadened as in the middle of deep breath, person find hard to breath
Depressed diaphragm with limited
mobility
Laboratory tests
Erythrocytosis
(advanced disease
)—-Too many red blood cells to carry oxygen to your organ and tissue.
Pulmonary function tests
Decreased vital capacity
Prolonged expiratory
flow (person’s maximum speed of expiration as measured with a peak flow meter)
Activity: Small Group Discussion
•
What
is the first line treatment
of
Pneumonia?
Treatment of chronic Bronchitis
The goals of therapy for chronic bronchitis are:
T
o
reduce the severity of chronic symptoms and
T
o
ameliorate acute exacerbations and achieve prolonged infection-free
intervals
Treatment of chronic
Bronchitis
Cont
…
Non-Pharmacological Treatment
Stop smoking and/or remove from hazardous environment
Prompt treatment of infective exacerbations
Antibiotics as above in case of secondary bacterial infection
Controlled oxygen therapy
Physiotherapy
Treatment of chronic
Bronchitis
Cont
……
Pharmacological Treatment
Inhaler
Salbutamol (PO) 100
μg
two puff 6 hourly
OR
Salbutamol (PO) 4mg 8 hourly
OR
Ipratropium bromide aerosol 20–80mg, 6–8 hourly
Trial of steroids if there is possibility of reversible airways obstructions
Prednisolone (PO) 20mg once daily for 5 days
Treatment of chronic Bronchitis
Cont
……
Pharmacological
Treatment..
Antibiotics
are probably helpful only in acute exacerbations of chronic bronchitis
Common current clinical practice is to promptly use antibiotics empirically in patients who demonstrate a fever or a change in sputum character.
Such therapy should be directed against streptococcal species, Haemophilus species and
Moraxella
catarrhalis
.
Treatment of chronic Bronchitis
Cont
……
Monitoring of Chronic Bronchitis Therapy
After therapy has been instituted, appropriate clinical parameters such as signs and symptoms and other laboratory markers such as lung function tests should be monitored to ensure the efficacy and safety of the therapeutic regimen.
Key Points
Pneumonia
is an infection of the lung tissue whereby the air sacs in the lungs become infected with microorganisms, fluid and inflammatory cells and hence they lungs fail to work properly.
Diagnosis of pneumonia is based on symptoms and signs of an acute lower respiratory tract infection, and can be confirmed by a chest X-ray showing new shadowing that is not due to any other cause
Penicillins as well as other antibiotics can be used for treatment of Pneumonia as indicated
Evaluation
What
is Chronic Bronchitis?
What are the signs and symptoms of Chronic Bronchitis?
How is Chronic Bronchitis diagnosed?
How is the treatment of Chronic Bronchitis?
REFER Students to Handout 9.1: Pharmacotherapy of Acute Bronchitis
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 10: Pharmacotherapy of Typhoid Fever
Learning Objectives
By the end of this session students are expected to be able to:
Define typhoid fever
Explain pathophysiology of typhoid fever
Explain the clinical presentation of typhoid fever
Outline diagnosis of typhoid fever
Describe pharmacological treatment of typhoid fever
Describe monitoring of typhoid fever therapy
Activity: Buzzing
is typhoid fever?
Definition of Typhoid Fever
Typhoid Fever
Typhoid fever, also called enteric fever, is caused by a bacterial infection with
Salmonella enterica
subspecies enterica serotype
Typhi
or serotypes
Paratyphi A, B or C
.
Infection is acquired through ingestion of contaminated food and water.
Humans are the only known hosts of
Salmonella Typhi
.
Bacteria are shed in the faeces of an infected person and transmitted from person to person via ingestion of food or water contaminated by these faeces (faecaloral route).
Definition of Typhoid Fever
Cont.….
Large outbreaks of typhoid fever are often associated with contamination of a drinking water.
Furthermore, the organism can survive for prolonged periods (up to several months) in contaminated foods
Pathophysiology Of Typhoid Fever
Once ingested and successfully beyond host defense mechanisms such as low gastric pH and bile salts, organisms can attach and invade the distal ileum and proximal colon.
Gastroenteritis often is characterized by massive neutrophil infiltration followed by lymphocytes and macrophages.
The serotypes that are responsible for human illness cause intestinal epithelial
cellsto
secrete interleukin 8, a potent neutrophil chemo-tactic factor.
Degranulation and release of toxic substances by neutrophils may contribute to inflammation and result in tissue damage, fluid secretion, or leakage across the intestinal mucosa
Clinical Presentation Of Typhoid Fever
Few clinical features reliably distinguish typhoid fever from other causes of febrile illnesses(temporary increase in average body temperature). Infection in the absence of treatment manifests after an average incubation period of 10-14 days (range 5-21 days) as a multistage febrile illness
.
Acute typhoid fever:
Systemic illness characterised by:
Fever: remittent during the first week, rising in a stepwise fashion and becomes sustained (lasting > 48 hours) after the first week.
Headache
Clinical Presentation Of Typhoid
Fever
Cont
….
Gastrointestinal symptoms including:
Abdominal pain/cramps
Nausea and vomiting (usually not severe), and/or
Constipation or diarrhoea (diarrhoea is more frequent in children and HIV infected adults).
Clinical presentation
cont.
…
Relative bradycardia
(slower heart rate)
Hepatosplenomegaly (23-65
%).——liver and spleen swell beyond normal size
Leukopenia (16-46
%).—— Low white blood count
Nonspecific symptoms, such as chills, diaphoresis, anorexia, cough, weakness, sore throat,
Dizziness, and muscle pains, are frequent before the onset of fever.
Severe illness and extra-intestinal complications may include;
gastrointestinal bleeding ,
intestinal perforation,
Septic shock or acidosis.
Blood culture is the diagnostic test of choice
Activity
: Small Group Discussion
is the first line treatment of Typhoid Fever??
Pharmacological Treatment Of Typhoid Fever
Monitoring of Typhoid fever Therapy
After therapy has been instituted, appropriate clinical parameters such as signs and symptoms and other laboratory markers should be monitored to ensure the efficacy and safety of the therapeutic regimen
Key
Points
It
is an acute systemic disease resulting from infection by Salmonella
typhi
and
S.paratyphi
,
serovar
group A and B respectively.
Infection is acquired through ingestion of contaminated food and water.
Patients may complain of nausea and vomiting followed by abdominal cramps, headache, fever, and diarrhea
Ciprofloxacin (PO) 500mg 12 hourly for 10 days
OR
Azithromycin (PO) Adult 500mg for 7 days can be used for treatment
Evaluation
What
is typhoid fever?
What is the pathophysiology of typhoid fever?
What are the signs and symptoms of acute typhoid fever?
How is the treatment of typhoid fever?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 11: Pharmacotherapy of
Amoebiasis
Learning Objectives
By the end of this session students are expected to be able to:
Define of amebiasis and
ameobic
liver abscess
Explain pathophysiology of amebiasis and
ameobic
liver abscess
Explain the clinical presentation of amebiasis and
ameobic
liver abscess
Outline diagnosis of amebiasis and
ameobic
liver abscess
Describe pharmacological treatment of amebiasis and
ameobic
liver abscess
Describe the monitoring of amebiasis and
ameobic
liver abscess therapy
Activity: Buzzing
is
Amoebiasis?
Definition of Amebiasis
Amebiasis
Amoebiasis is an infection caused by the protozoa organism
Entamoeba histolytica,
which can cause colitis and other extra-intestinal manifestations.
The infection is primarily acquired through ingestion of contaminated food and water and occasionally can be acquired through oral-anal sexual practices.
Amoebic Liver Abscess
It is the most frequent extra-intestinal manifestation of
Entamoeba histolytica
infection which results from the invasion of the portal venous system from the colon leading to inflammation and subsequently abscess formation particularly involving the right lobe of the liver.
Pathophysiology Of Amoebiasis
E histolytica
invades mucosal cells of colonic epithelium, producing the classic flask-shaped ulcer in the submucosa.
The trophozoite has a
cytolethal
effect on cells through a toxin.
If the trophozoite gets into the portal circulation, it will be carried to the liver, where it produces abscess and
periportal
fibrosis.
Amebic ulcerations can affect the colon, perineum, and genitalia, and abscesses may occur in the lung and brain.
Clinical Presentation Of Amoebiasis
Intestinal disease
Vague abdominal discomfort, malaise to severe abdominal cramps, flatulence,
bloody diarrhea (
heme
-positive in 100% of cases) with mucus
Eosinophilia is usually absent, although moderate leukocytosis is not unusual
Evidence of motile
trophozoites
or cysts on saline wet mount from a stool specimen
Clinical Presentation Of Amoebiasis Cont.…
Amebic liver abscess
High fever, rigors(sudden feeling of cold and shivering) and profuse sweating,
significant leukocytosis with left shift,
elevated alkaline phosphatase, and liver tenderness on palpation
Right-upper-quadrant pain, hepatomegaly, and liver tenderness, with referred
painto
the left or right shoulder
Erosion of liver abscesses may also present as peritonitis(inflammation of the membrane lining the
abnominal
wall and covering the
abnominal
organs).
Positive imaging evidence of liver abscess and Serological evidence of
E.
histolytica
antibodies or antigens.
Activity
: Small Group Discussion
is the
treatments
of
amebiasis?
Pharmacological treatment and diagnosis of Amoebiasis
Monitoring Of Amoebiasis Therapy
Follow up in patients with amebiasis should include;
repeat stool examination, serology, colonoscopy (for colitis), or
Computed tomography (CT) (for liver abscess) between days 5 and 7, at the end of the course of therapy, and a month after the end of therapy.
Most patients with either intestinal amebiasis or colitis will respond in 3 to 5 days with amelioration of symptoms.
Monitoring Of Amoebiasis
Therapy Cont.…
Patients with liver abscesses may take from 7 to 10 days to respond;
Patients not responding during this period may require aspiration of abscesses or exploratory laparotomy.
Serial liver scans have demonstrated healing of liver abscesses over 4 to 8 months after adequate therapy.
Key
Points
Amebiasis
is a parasitic infection of the intestines caused by the protozoan Entamoeba histolytica, or E. histolytica.
Infection
by Entamoeba histolytica occurs by ingestion of mature cysts
infecally
contaminated food, water, or hands
The
symptoms of amebiasis include loose stool, abdominal cramping, and stomach
pain
Treatment for uncomplicated cases of amebiasis generally consists of a course of
metronidazole
or
tinidazole
Evaluation
What
is Amebiasis?
What is the pathophysiology of amebiasis?
What are the signs and symptoms of Amebiasis?
How is the treatment of Amebiasis?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-
PST 06106
Basic Pharmacotherapy
Session 12: Pharmacotherapy of Trypanosomiasis
Learning objectives
By the end of this session students are expected to be able to:
Define trypanosomiasis
Explain the clinical presentation of trypanosomiasis
Outline diagnosis of trypanosomiasis
Describe pharmacological treatment of trypanosomiasis
Describe monitoring of trypanosomiasis therapy
Activity: Buzzing
What is Trypanosomiasis?
Definition of Trypanosomiasis
Two distinct forms of the genus
Trypanosoma
occur in humans.
One is associated with African trypanosomiasis (sleeping sickness) and the other with American trypanosomiasis (Chagas disease)
Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease.
The parasites concerned are protozoa belonging to the Trypanosoma genus.
They are transmitted to humans by tsetse fly (
Glossina
genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic
parasites
Definition of Trypanosomiasis
Cont
…
Two forms of the disease exist.
The slow-progressing form, caused by
Trypanosoma
brucei
gambiense
, is found in Western and Central Africa.
The faster progressing form, caused by T. b.
rhodesiense
, is found in Eastern and Southern Africa
Mother-to-child infection: the trypanosome can cross the placenta and infect the
fetus
.
Mechanical transmission through other blood sucking insects is possible.
Accidental infections have occurred in laboratories due to pricks from contaminated needles.
Clinical presentation of Trypanosomiasis
In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph.
This is known as a
haemolymphatic
phase, which entails bouts of fever, headaches, joint pains and itching.
After their inoculation, parasites proliferate at the site of infection, leading to an inflammatory nodule or ulcer.
This trypanosomal chancre arises in about 50% of all rhodesiense—but rarely in gambiense—infections.
After 3–4 weeks, the chancre usually heals with overlying desquamation, sometimes with altered pigmentation.
Parasites spread to the draining lymph node and reach the bloodstream, initiating the
haemolymphatic
stage of the disease.
This stage is characterised by general malaise, headache, and fever of an undulating type.
In rhodesiense infection, with its more acute course,
pancarditis
with congestive heart failure, pericardial effusion, and pulmonary oedema can cause fatalities at this early stage, whereas gambiense infection shows a more insidious development that is frequently unrecognised or misdiagnosed.
A typical sign of
gambiense
human African
trypanosomiasis
is generalised lymphadenopathy that develops after several weeks, frequently in the posterior triangle of the neck
Clinical
presentation of Trypanosomiasis
cont.
…
In the second stage the parasites cross the blood-brain barrier to infect the central nervous system.
This is known as the neurological phase.
In general this is when more obvious signs and symptoms of the disease appear: changes of behaviour, confusion, sensory disturbances and poor coordination.
Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease.
Diagnosis of Trypanosomiasis
The diagnosis of African Trypanosomiasis is made through laboratory methods, because the clinical features of infection are not sufficiently specific.
The diagnosis rests on finding the parasite in body fluid or tissue by microscopy.
The parasite load in
T. b. rhodesiense
infection is substantially higher than the level in
T. b. gambiense
infection.
T. b. rhodesiense
parasites can easily be found in blood.
Diagnosis of Trypanosomiasis
Cont
…
They can also be found in lymph node fluid or in fluid or biopsy of a chancre.
The classic method for diagnosing
T. b. gambiense
infection is by microscopic examination of lymph node aspirate, usually from a posterior cervical node.
It is often difficult to detect
T. b. gambiense
in blood. Concentration techniques and serial examinations are frequently needed.
Serologic testing is available outside the U.S. for
T. b. gambiense
; however, it normally is used for screening purposes only and the definitive diagnosis rests on microscopic
Diagnosis of Trypanosomiasis
Cont
…
All patients diagnosed with African trypanosomiasis must have their cerebrospinal fluid examined to determine whether there is involvement of the central nervous system, since the choice of treatment drug(s) will depend on the disease stage.
The World Health Organization criteria for central nervous system involvement include increased protein in cerebrospinal fluid and a white cell count of more than 5.
Trypanosomes can often be observed in cerebrospinal fluid in persons with second stage infection
.
Activity
: Small Group Discussion
What
is the
treatment
of Trypanosomiasis?
Pharmacological treatment of Trypanosomiasis
The type of treatment depends on the stage of the disease.
The drugs used in the first stage of the disease are of lower toxicity and easier to administer.
The earlier the disease is identified, the better the prospect of a cure.
Treatment success in the second stage depends on a drug that can cross the blood-brain barrier to reach the parasite.
Such drugs are toxic and complicated to administer.
Monitoring of Trypanosomiasis Therapy
Monitor clinically and by using laboratory test
In both early- and late-stage trypanosomiasis, symptoms usually resolve after treatment, and the
parasitemia
clears on repeat blood smears.
Patients who have recovered from late-stage East African trypanosomiasis should undergo
lumbar punctures
every 3 months for the first year.
Patients who have recovered from West African trypanosomiasis should undergo lumbar punctures every 6 months for 2 years
.
Monitoring of Trypanosomiasis
Therapy
Cont
….
If symptoms return, the CSF WBC count is higher than 20/µL, CSF
pleocytosis
occurs((presence of an abnormally large number lymphocytes in cerebrospinal fluid), or trypanosomes are still present in blood or CSF, a relapse is suggested.
However, a persistently elevated CSF WBC count may also be observed in recovering patients; thus, the change (increase or decrease) in the WBC count is more diagnostically helpful than the count by itself.
If a relapse is noted, repeat treatment with
melarsoprol
or
eflornithine
may be considered
Key Points
Human
African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease.
It is caused by infection with protozoan parasites belonging to the genus
Trypanosoma
.
They are transmitted to humans by tsetse fly (
Glossina
genus) bites which have acquired their infection from human beings or from animals harbouring human pathogenic parasites.
The type of treatment depends on the disease stage whereby drugs used in the first stage are safer and easier to administer than those for second stage.
Also, the earlier the disease is identified, the better the prospect of a cure
.
Evaluation
What
is trypanosomiasis?
What is the pathophysiology of trypanosomiasis?
What are the signs and symptoms of trypanosomiasis?
How is the treatment of trypanosomiasis?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 13: Pharmacotherapy of Schistosomiasis
Learning tasks
By the end of this session students are expected to be able to:
Define
schistosomiasis
Explain pathophysiology of schistosomiasis
Explain the clinical presentation of schistosomiasis
Outline diagnosis of schistosomiasis
Describe pharmacological treatment of schistosomiasis
Describe monitoring of schistosomiasis therapy
Activity: Buzzing
What
is
Schistosomiasis
?
Definition of Schistosomiasis
Schistosomiasis
Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus
Schistosoma
.
Definition of Schistosomiasis
Cont
…
There are 2 major forms of schistosomiasis which are intestinal and urogenital caused by 5 main species of blood fluke as follows
;
Definition of Schistosomiasis
Cont
….
Infection happens when larval forms of the parasite released by freshwater snails penetrate the skin during contact with infested water.
Transmission occurs when infected individual from schistosomiasis contaminate freshwater sources with their excreta containing parasite eggs, which hatch in water.
In the body, the larvae develop into adult
schistosomes
.
Adult worms live in the blood vessels where the females release eggs.
Some of the eggs are passed out of the body in the
faeces
or urine to continue the parasite’s lifecycle.
Others become trapped in body tissues, causing immune reactions and progressive damage to organs
.
Pathophysiology and Symptoms of Schistosomiasis
In schistosomiasis, adult worms reside in the mesenteric and pelvic venules in various sites where they lay eggs
These sites tend to be specific for each species (e.g.
S.
japonicum
prefers the superior mesenteric veins draining to the small intestine, while
S.
mansoni
prefers the superior mesenteric veins of the large intestine)
Many eggs are carried upstream where they get lodged in various organs, especially in the liver, bowel, and genitourinary tract
Acute disease may trigger a cell-driven inflammatory response (involving tumour necrosis factor, interleukin-1, and interleukin-6 cytokines) and cause febrile illness
Pathophysiology and Symptoms of Schistosomiasis
Cont..
As mature female worms lay eggs, products of worm and egg metabolism induce formation of immune complexes resulting to a serum like-sickness called Katayama syndrome
In chronic disease, eggs are the cause of pathology; they evoke a Thelper type 2 (Th2) cell-driven granulomatous reaction (involving interleukin-4, interleukin-5, and interleukin-13 cytokines) resulting in tissue fibrosis and chronic morbidity
Gastrointestinal schistosomiasis due to S.
mansoni
, S.
japonicum
and S.
mekongi
can cause bowel lesions such as ulceration,
pseudopolyps
(masses of scar tissue during healing), and
microabcesses
.
These manifest clinically as abdominal pain, altered bowel habits, and blood in stools
Pathophysiology and Symptoms of Schistosomiasis
Cont
…
The
classic sign of urogenital schistosomiasis is haematuria and is specifically noted with
S.
haematobium
Bladder, ureter fibrosis and kidney damage are sometimes seen in advanced cases
The urogenital form may present with genital lesions (e.g. vulvar nodules), vaginal bleeding,
dyspareunia(painful intercourse) ,
and fallopian tube damage (in the late stages) in females
Genital infection in males may
result in
damage to seminal vesicles, prostate and other related organs; this may lead to irreversible infertility
Clinical Presentation of Schistosomiasis
Symptoms of schistosomiasis are caused by the body’s reaction to the worms' eggs.
Intestinal schistosomiasis can result in abdominal pain,
diarrhoea
, and blood in the stool.
Liver enlargement is common in advanced cases, and is frequently associated with an accumulation of fluid in the peritoneal cavity and hypertension of the abdominal blood vessels.
In such cases there may also be enlargement of the spleen.
The classic sign of urogenital schistosomiasis is
haematuria
(blood in urine).
Clinical Presentation of Schistosomiasis
Cont
…
Fibrosis of the bladder and ureter, and kidney damage are sometimes diagnosed in advanced cases.
Bladder cancer is another possible complication in the later stages. In women, urogenital schistosomiasis may present with genital lesions, vaginal bleeding, pain during sexual intercourse, and nodules in the vulva.
In men, urogenital schistosomiasis can induce pathology of the seminal vesicles, prostate, and other organs.
This disease may also have other long-term irreversible consequences, including infertility.
Diagnosis of Schistosomiasis
Schistosomiasis is diagnosed through the detection of parasite eggs in stool or urine specimens
Antibodies and/or antigens detected in blood or urine samples are also indications of infection
For urogenital schistosomiasis, a filtration technique using nylon, paper or polycarbonate filters is the standard diagnostic technique
Children with
S.
haematobium
almost always have microscopic blood in their urine which can be detected by chemical reagent
strips
Diagnosis of
Schistosomiasis
Cont
…
The eggs of intestinal schistosomiasis can be detected in
faecal
specimens through a technique using methylene blue-stained cellophane soaked in
glycerine
or glass slides, known as the Kato-Katz technique
For people living in non-endemic or low-transmission areas, serological and immunological tests may be useful in showing exposure to infection and the need for thorough examination, treatment and follow-up
Activity
: Small Group Discussion
is the
treatment
of Schistosomiasis?
Pharmacological Treatment of Schistosomiasis
The control of schistosomiasis is based on large-scale treatment of at-risk population groups, access to safe water, improved sanitation, hygiene education, and snail control.
The WHO strategy for schistosomiasis control focuses on reducing disease through periodic, targeted treatment with
praziquantel
through the large-scale treatment (preventive chemotherapy) of affected populations.
It involves regular treatment of all at-risk groups.
Groups targeted for treatment are:
School-aged children in endemic areas.
Pharmacological Treatment of
Schistosomiasis
Cont
…
Adults considered to be at risk in endemic areas, and people with occupations involving contact with infested water, such as fishermen, farmers, irrigation workers, and women whose domestic tasks bring them in contact with infested water.
Entire communities living in highly endemic areas.
In high-transmission areas, treatment may have to be repeated every year for a number of years.
Monitoring is essential to determine the impact of control interventions
.
Monitoring Of Schistosomiasis Therapy
Follow-up of treatment response in schistosomiasis needs to be guided by active disease parameters, such as suggestive symptoms, raised eosinophil count, or parasitological/histological evidence of viable eggs
If symptoms such as hematuria or bloody diarrhea persist for weeks after treatment, urine or stool samples should be tested for parasite eggs and appropriate action should be taken depending on the results
Serological assays of the levels of anti-
schistosome
-egg antibodies can also be used in the post-treatment monitoring to confirm
for
treatment
success or failure
from
praziquentel
.
Key Points
Schistosomiasis
is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus
Schistosoma
.
People become infected when larval forms of the parasite are released by freshwater snails and then penetrate the skin during contact with infested water.
Transmission occurs when people suffering from schistosomiasis contaminate freshwater sources with their excreta containing parasite eggs, which hatch in water.
The classic sign of urogenital schistosomiasis is haematuria (blood in urine
Praziquantel is the recommended treatment against all forms of schistosomiasis
Evaluation
What
is Schistosomiasis?
What is the pathophysiology of
Schistosomiasis?
What are the signs and symptoms of Schistosomiasis?
How is the treatment of Schistosomiasis
?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 14: Pharmacotherapy
of
Gonorrhea
Learning Objective
By the end of this session students are expected to be able to:
Define
gonorrhoea
Explain pathophysiology of gonorrhoea
Explain the clinical presentation of gonorrhoea
Outline diagnosis of gonorrhoea
Describe pharmacological treatment of gonorrhoea
Describe monitoring of gonorrhoea
therapy
Activity: Buzzing
•What
is
Gonorrhoea
?
Definition of
Gonorrhea
Gonorrhea
is a
sexually transmitted disease (
STD)
caused
by infection with the bacterium
Neisseria gonorrhoeae
.
It tends to infect warm, moist areas of the body, including the:
U
rethra
(the tube that drains urine from the urinary bladder)
E
yes
T
hroat
V
agina
A
nus
F
emale
reproductive tract
(the fallopian tubes, cervix, and uterus)
Definition of Gonorrhea
Gonorrhea is transmitted from person to person through unprotected oral, anal, or vaginal sex.
People with numerous sexual partners or those who don’t use a condom are at greatest risk of infection
.
Pathophysiology of
Gonorrhea
On contact with a mucosal surface lined by columnar, cuboidal, or
noncornified
squamous epithelial cells, the gonococci attach to cell membranes by means of surface pili and are then
pinocytosed
.
The virulence of the organism is mediated primarily by the presence of pili and other outer membrane proteins.
After mucosal damage is established,
polymorphonuclear
(PMN) leukocytes invade the tissue, submucosal abscesses form, and purulent exudates are secreted
.
Clinical Presentation of Gonorrhea
Individuals infected with gonorrhea can be;
symptomatic or asymptomatic,
have complicated or uncomplicated infections, and
Have infections involving several anatomic sites.
Complications
associated with untreated gonorrhea appear more pronounced in women, because most of them are asymptomatic
As a result, most of these patients develop serious complications, such as;
pelvic inflammatory disease (PID),
Infertility and ectopic pregnancies.
In other patients the gonococci invade the bloodstream and produce disseminated disease
Diagnosis of
Gonorrhea
Diagnosis of gonococcal infections can be made by ;
gram-stained smears,
culture, or
Methods based on the detection of cellular components of the gonococcus such as Enzyme immunoassay, DNA probe techniques, and nucleic acid amplification techniques (NAATs) are also used in clinical specimens.
Various stains have been used to identify gonococci microscopically, with the Gram stain the most widely used in clinical practice.
Gram-stained smears are positive for gonococci when gram-negative diplococci of typical kidney bean morphology are identified within PMN leukocytes.
Activity
: Small Group Discussion
What
is the
treatment
of Gonorrhoea?
Pharmacological treatment of gonorrhea
Uncomplicated gonococcal infection
Recommended Regimen
Ceftriaxone 250mg IM in a single dose
PLUS
Azithromycin 1g orally in a single dose
Alternative regimen
If ceftriaxone is not available.
Cefixime
400mg orally in a single dose
plus
Azithromycin 1g orally in a single dose
Treatment of various forms of
Gonorrhea
Infection
Monitoring Of Gonorrhea Therapy
It is recommended to obtain follow-up cultures at least 3 days after treatment
However the combination gonorrhea and chlamydial therapy rarely results in treatment failures, and routine follow-up of patients treated with a regimen is not necessary.
Persistence of symptoms following any treatment requires culture of the site(s) of gonorrheal infection, as well as susceptibility testing if gonococci are isolated.
Monitoring Of Gonorrhea
Therapy Cont..
In most cases, the presence of gonococci indicates reinfection rather than treatment failure and reflects the need for improved patient education and sex partner referral.
Persistence of symptoms also can be caused by other infectious causes, such as C. trachomatis
Key Points
Gonorrhea
is a sexually transmitted disease (STD).
It’s
caused by infection with the bacterium Neisseria
gonorrhoeae
Gonorrhea
passes from person to person through unprotected oral, anal, or vaginal
sex.
First
line drug treatment with
Cetriaxone
and Azithromycin is recommended
Evaluation
What
is Gonorrhoea?
What is the pathophysiology of Gonorrhoea?
What are the signs and symptoms of Gonorrhoea?
How is the treatment of Gonorrhoea?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 15: Pharmacotherapy of Syphilis
Learning Task
By the end of this session students are expected to be able to:
Define syphilis
Explain the clinical presentation of syphilis
Outline diagnosis of syphilis
Describe pharmacological treatment of syphilis
Describe the monitoring of syphilis
therapy
.
Activity: Buzzing
is syphilis??
Definition of Syphilis
Syphilis
Syphilis is an infectious venereal disease caused by the spirochete
Treponema pallidum
.
Syphilis is transmissible by sexual contact with infectious lesions, from mother to fetus in utero, via blood product transfusion, and occasionally through breaks in the skin that come into contact with infectious lesions.
If untreated, it progresses through 4 stages: primary, secondary, latent, and tertiary
Clinical Presentation
Primary Syphilis
The primary stage, characterized by the appearance of a chancre on cutaneous or mucocutaneous tissue exposed to the organism, is highly infectious.
Even without treatment, chancres persist only for 1 to 8 weeks before healing spontaneously. Because syphilitic chancres can be confused with other infectious etiologies, appropriate diagnostic testing is important
.
Clinical
Presentation
Cont
…
Secondary Syphilis
The secondary stage of syphilis is characterized by a variety of mucocutaneous eruptions resulting from widespread
hematogenous
and lymphatic spread of
T. pallidum
.
Skin lesions can be either generalized or localized to a small portion of the body and, with the exception of follicular lesions, are
nonpruritic
.
Generalized lymphadenopathy also is seen in the majority of patients, as are nonspecific symptoms such as mild and transitory malaise, fever, pharyngitis, headache, anorexia, and arthralgia.
If untreated, secondary syphilis disappears in 4 to 10 weeks; however, lesions can recur at any time within 4 years.
Clinical Presentation
Cont
…
Latent Syphilis
These are persons with a positive serologic test for syphilis but with no other evidence of disease.
Latent syphilis is further divided into early and late latency.
During early latency, the patient is considered potentially infectious.
Early latency is
defined as 1 year from the onset of infection, up to 2 to 4 years.
Late latency is considered noninfectious, although the patient remains a host.
Most untreated patients with late latent syphilis have no further sequelae; however, approximately 25% to 30% progress either to neurosyphilis or to late syphilis with clinical manifestations other than neurosyphilis.
Treatment of all patients with latent syphilis is essential because there is no way to predict which patients will have progression of their disease
Clinical Presentation
Cont
…
Tertiary Syphilis and
Neurosyphilis
If
left untreated, syphilis can slowly produce an inflammatory reaction in virtually any organ in the body.
Manifestations of this disease progression are referred to as
tertiary syphilis.
These clinical manifestations are differentiated into two subgroups based on the presence or absence of central nervous system (CNS) involvement which are neurosyphilis or tertiary syphilis (i.e., gumma and cardiovascular syphilis).
The gumma, a nonspecific granulomatous lesion, is the classic lesion of late syphilis and develops in 50% of patients with disease progression.
These chronic, destructive lesions characteristically infiltrate the skin, bone, soft tissue, and liver but can be found in any organ or tissue.
Gummas of critical organs, such as the heart or brain, can be fatal
Clinical Presentation Of Syphilis
Diagnosis Of Syphilis
Syphilis diagnosis is based on the;
patient’s history,
physical examination,
laboratory testing and
Radiology
Diagnosis of
Sphilis
Cont
…
The available laboratory tests for diagnosis of syphilis include
D
irect
detection methods (i.e.
dark field
microscopy, direct fluorescent antibody test and nucleic acid amplification test),
S
erology
tests such as;
Treponemal tests which include the Treponema pallidum
haem- agglutination
assay (TPHA), the Treponema pallidum particle agglutination assay (TPPA) and the fluorescent treponemal antibody absorbed (FTA-ABS) tests
Non-treponemal tests (the microscopic Venereal Diseases Research Laboratory -VDRL and the macroscopic rapid plasma
reagin
–RPR tests),
Examination of cerebrospinal fluids
Rapid diagnostic tests (RDTs) for treponemal antibodies in syphilis infection
Activity
: Small Group Discussion
is the
treatment
of
Syphilis
?
Pharmacological Treatment
Parenteral penicillin G is the treatment of choice for all stages of syphilis.
Because
T. pallidum
multiplies slowly, single doses of short- or intermediate-acting penicillins do not provide the prolonged, low-level exposure to penicillin required for eradication of the
treponeme
.
A result, benzathine penicillin G is the only penicillin effective for single-dose therapy.
The recommended treatment for syphilis of less than 1 year’s duration is benzathine penicillin G 2.4 million units as a single dose.
Units can be administered once a week for 2 consecutive weeks.
In patients with syphilis of longer than 1 year’s duration and normal CSF examination, benzathine penicillin G is administered weekly for three successive doses
Monitoring Of Syphilis Therapy
Non treponemal tests should be performed at 6 and 12 months in all patients
treated
for
primary and secondary syphilis and at 6, 12, and 24 months for early and late latent disease.
More frequent monitoring of HIV-infected individuals (i.e., 3, 6, 9, 12, and 24 months after therapy) should be done
In general, the time to reach seronegativity is proportional to the duration of the
disease.
Despite adequate therapy, some patients can remain seropositive based on
non- treponemal
test results.
In these cases, stabilization of low antibody titers is indicative of adequate therapy.
For women treated during pregnancy, monthly quantitative
non-treponemal
tests are recommended in those at high risk of reinfection.
Key Points
Syphilis
is a systemic disease from the outset and is caused by the
spirochaete
,
Treponema
pallidum (T. pallidum)
The infection can be classified as congenital (transmitted from mother to child in utero) or acquired (through sex or blood transfusion)
Acquired syphilis is divided into early and late syphilis
Early syphilis comprises the primary, secondary and early latent stages while late syphilis refers to late latent syphilis,
gummatous
, neurological and cardiovascular syphilis
Long-acting benzathine
benzylpenicillin
provides optimal
treponemicidal
penicillinaemia
and is recommended for syphilis treatment
Evaluation
What
is Syphilis?
What are the signs and symptoms of syphilis?
What is the treatment of Syphilis?
How will you monitor patient on syphilis therapy
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 16: Pharmacotherapy of Chlamydial Genital Tract Infections
Learning Tasks
By the end of this session students are expected to be able to
:
Define
chlamydial genital tract infections
Explain pathophysiology of chlamydial genital tract infections
Explain the clinical presentation of chlamydial genital tract infections
Outline diagnosis of chlamydial genital tract infections
Describe pharmacological treatment of chlamydial genital tract infections
Describe the monitoring of chlamydial genital tract infections therapy
Activity: Buzzing
What
is Chlamydial Genital Tract Infections?
Definition of Chlamydial Genital Tract Infections
Chlamydial Genital Tract Infections
Chlamydial Genital Tract Infections is a sexually transmissible infection caused by bacterium
Chlamydia
t
rachomatis
Persons infected with the bacterium may not have symptoms of infection but can still transmit the bacterium.
Chlamydia can affect the urethra (the urine passage), cervix (the neck of the womb), rectum and anus, throat, and eyes
.
Pathophysiology of Chlamydial Genital Tract Infections
is an obligate intracellular parasite that shares properties of both viruses and bacteria.
Like viruses,
chlamydiae
require cellular material from host cells for replication; however, unlike viruses,
chlamydiae
maintain their cellular identity throughout development.
Although
lacks a cell-wall peptidoglycan, its major outer membrane is similar to gram-negative bacteria.
At least 18
serovars
(subspecies) of
exist, of which only the lymphogranuloma venereum strains produce potentially invasive infections.
The remaining
serovars
are involved primarily with superficial infection of epithelial cells
.
Pathophysiology of Chlamydial Genital Tract
Infections Cont
..
Chlamydia have the ability to establish long-term associations with host cells.
When an infected host cell is starved for various nutrients such as amino acids (for example, tryptophan), iron, or vitamins, this has a negative consequence for Chlamydiae since the organism is dependent on the host cell for these nutrients.
The starved
Chlamydiae
enter a persistent growth state wherein they stop cell division and become morphologically aberrant by increasing in size.
Persistent organisms remain viable as they are capable of returning to a normal growth state once conditions in the host cell improve and causing chronic
Clinical
Presentation of Chlamydial Genital Tract Infections
In comparison with gonorrhea, chlamydial genital tract infections are more frequently asymptomatic, and when present, symptoms tend to be less noticeable.
Urethral discharge usually is less profuse and more mucoid or watery than the urethral discharge associated with gonorrhea.
Diagnosis of Chlamydia Genital tract infection
A sample of urine can be collected and analyzed in the laboratory to investigate the presence of this infection.
A swab of the discharge can be collected for culture or antigen testing for chlamydia.
Nucleic Acid Amplification Tests
(NAAT), such
as
Polymerase Chain Reaction
(PCR
),
Transcription Mediated Amplification
(
TMA), and the DNA
Strand Displacement Amplification
(SDA) now are the mainstays.
NAAT for chlamydia may be performed on swab specimens sampled from the cervix (women) or urethra (men), on self-collected vaginal swabs, or on voided urine
Activity
: Small Group Discussion
What
is the treatment of Chlamydial Genital Tract Infections?
Pharmacological treatment of Chlamydial Genital Tract infection
Monitoring of chlamydial Genital Tract Infections Therapy
Treatment of chlamydial infections with the recommended regimens is highly effective; therefore, post-treatment laboratory testing is not recommended routinely unless symptoms persist or there are other specific concerns (e.g., pregnancy).
Post-treatment tests should not be performed for at least 3 weeks following
completion
of
therapy.
When post-treatment tests are positive, they usually represent noncompliance, failure to treat sexual partners, or laboratory error rather than inadequate therapy or resistance to therapy.
Infants with pneumonitis should receive follow-up testing because erythromycin is only 80% effective, and a second course of therapy can be necessary
Key
Points
Chlamydia
is a sexually transmissible infection caused by bacterium
Chlamydia
t
rachomatis
Persons infected with the bacterium may not have symptoms of infection but can still transmit the bacterium.
Azithromycin is drug of choice for the treatment of chlamydia infection
Evaluation
What
is
Chlamydia
infection?
What is the pathophysiology of
Chlamydial
infection?
What are the signs and symptoms of
Chlamydia
infection?
How is the treatment of
Chlamydia
Infection?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 17: Pharmacotherapy of Genital Herpes
Learning Tasks
By the end of this session students are expected to be able to:
Define genital herpes
Explain pathophysiology of genital herpes
Explain the clinical presentation of genital herpes
Outline diagnosis of genital herpes
Describe pharmacological treatment of genital herpes
Describe the monitoring of genital herpes
therapy
Activity: Buzzing
is Genital
Herpes?
Definition of Genital Herpes
Genital Herpes
Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus (HSV).
Sexual contact is the primary way that the virus spreads.
There are two types of Herpes Simplex viruses; herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2).
HSV-1 is associated most commonly with oropharyngeal disease, and HSV-2 is associated most closely with genital disease;
However, each virus is capable of causing clinically indistinguishable infections in both anatomic areas.
Definition of Genital Herpes
Cont.….
Humans are the sole known reservoir for HSV.
Infection is transmitted via inoculation of virus from infected secretions onto mucosal surfaces (e.g., urethra, oropharynx, cervix, and conjunctivae) or through abraded skin.
The cycle of HSV infection occurs in five stages: primary muco-cutaneous infection, infection of the ganglia, establishment of latency, reactivation, and recurrent infection
Pathophysiology Of Genital Herpes
After viral inoculation, HSV infection is associated with cytoplasmic
granulation(condensed areas of cellular material that may be bounded by a membrane),
ballooning degeneration of
cells (cells undergoing this form of death increase in size(balloon),
and production of
mononucleated
giant
cells ( cells formed by fusion of monocytes/macrophage)
Initially, the cellular response is predominantly
polymorph nuclear,
followed by a lymphocytic response.
Replication occurs with viral spread to contiguous cells and peripheral sensory nerves. Latency then is established in sensory or autonomic nerve root ganglia.
Latency appears to be lifelong, interrupted only by reactivation of the viral infection.
It is unclear what factors are important in maintaining latency, but immune responses and emotional and physical stresses appear important in reactivating latent virus.
Clinical Presentation Of Genital Herpes
The signs and symptoms of genital herpes infection are
influenced by
many factors, including previous exposure to HSV, viral type, and host factors such as age and site of infection.
High percentage of initial and recurrent infections are asymptomatic,
Viral shedding can occur in the absence of apparent lesions or symptoms
A summary of the clinical presentation of genital herpes is provided in Table
Diagnosis Of Genital Herpes
A presumptive diagnosis of genital herpes commonly is made based on the presence of
dark-field negative
, vesicular, or ulcerative genital lesions.
A prior history of similar lesions or recent sexual contact with an individual with similar lesions also is useful in making the diagnosis
Viral culture. This test involves taking a tissue sample or scraping of the sores for examination in the laboratory
.
Diagnosis Of Genital
Herpes
Cont
….
Polymerase chain reaction (PCR) test. PCR is used to copy patient DNA from a blood sample, tissue from a sore or spinal fluid.
The DNA can then be tested to establish the presence of HSV and determine which type of HSV you have.
Blood test. This test analyzes a sample of blood for the presence of HSV antibodies to detect a past herpes infection.
Several serologic tests capable of distinguishing HSV-1 and HSV-2 antibodies are available.
These tests detect antibodies to type-specific HSV-1 and HSV-2 proteins gG-1 and gG-2, respectively
Activity
: Small Group Discussion
What
is the treatment of Genital Herpes?
Pharmacological Treatment of Genital Herpes
The most achievable goals in the management of genital herpes are to relieve symptoms and to shorten the clinical course, to prevent complications and recurrences, and to decrease disease transmission.
Although research has focused primarily on the treatment of active infection and suppression of recurrences, increasing emphasis is being placed on various approaches, including immunotherapy that might provide protection from disease transmission or possibly eliminate established latency.
.
Pharmacological Treatment of Genital Herpes
Oral formulations of acyclovir,
famciclovir
, and
valacyclovir
have demonstrated efficacy in reducing viral shedding, duration of symptoms, and time to healing of first-episode genital herpes infections, with maximal benefits seen when therapy is initiated at the earliest stages of infection
Pharmacological Treatment of Genital Herpes
Monitoring of Genital Herpes Therapy
Available antiviral compounds are of greatest benefit in patients experiencing first-episode primary infections, immunocompromised patients, and patients with frequent or severe recurrent infections.
Antivirals, however, are palliative and not curative, and patients receiving these agents should be monitored closely for adverse drug effects.
Discontinuation of suppressive therapy after 1 year should be considered to assess for possible changes in the patient’s intrinsic pattern of recurrence.
In many patients, decreases in recurrence rates and the severity of symptoms occur over time. However, it is also
preferred
to continue suppressive therapy indefinitely because it significantly reduces asymptomatic viral shedding, a potential benefit in reducing the risk of disease transmission to uninfected sexual partners
Key
Points
Genital
herpes is a common sexually transmitted infection caused by the herpes simplex virus (HSV).
Infection is transmitted via inoculation of virus from infected secretions onto mucosal surfaces (e.g., urethra, oropharynx, cervix, and conjunctivae) or through abraded skin
The signs and symptoms of genital herpes infection are
influencedby
many factors, including previous exposure to HSV, viral type, and host factors such as age and site of infection
Oral formulations of acyclovir,
famciclovir
, and
valacyclovir
have demonstrated efficacy in the treatment of genital herpes
Evaluation
What
is genital herpes?
What is the pathophysiology of
genital herpes?
What are the signs and symptoms of genital herpes?
How is the treatment of genital herpes?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 18:
Pharmacotherapy of Urinary Tract Infections
Learning Objectives
By the end of this session students are expected to be able to
:
Define
urinary tract infections
Explain pathophysiology of urinary tract infections
Explain the clinical presentation of urinary tract infections
Outline diagnosis of urinary tract infections
Describe pharmacological treatment of urinary tract infections
Describe the monitoring of urinary tract infections
therapy
Activity: Buzzing
What
is Urinary Tract Infections?
Definition of Urinary Tract Infections
Urinary Tract Infections (UTI
)
UTI is defined as the presence of microorganisms in the urinary tract that cannot be accounted for by contamination.
The organisms present have the potential to invade the tissues of the urinary tract and adjacent structures.
Infection may be limited to the growth of bacteria in the urine, which frequently may not produce symptoms.
A UTI can present as several syndromes associated with an inflammatory response to microbial invasion and can range from asymptomatic bacteriuria to pyelonephritis with bacteremia or sepsis.
Definition of Urinary Tract Infections
Cont.….
UTIs are classified by lower and upper urinary tract infections.
Upper tract infection include pyelonephritis (an infection involving the kidneys) represents
Lower
tract infections correspond to cystitis (bladder),
Also, UTIs are designated as uncomplicated or complicated.
Uncomplicated infections occur in individuals who lack structural or functional abnormalities of the urinary tract that interfere with the normal flow of urine or voiding mechanism.
Definition of Urinary Tract Infections
Cont.….
These infections occur in females of child-bearing age (15 to 45 years) who are otherwise
normal healthy individuals.
Complicated UTIs are the result of a predisposing lesion of the urinary tract, such as a congenital abnormality or distortion of the urinary tract, a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal
Classification of UTI
Pathophysiology of Urinary Tract Infections
The bacteria causing UTIs usually originate from bowel flora of the host.
Although virtually every organism is associated with UTIs, certain organisms predominate as a result of specific virulence factors.
The most common cause of UTIs is
Escherichia coli
, which accounts for 80% to 90% of community-acquired
infections.
Additional causative organisms in uncomplicated infections
include
Staphylococcus
saprophyticus
,
Klebsiella
pneumoniae, Proteus
spp.,
Pseudomonas aeruginosa
, and
Enterococcus
spp.
Pathophysiology
cont
…
Pathogenic organisms have differing degrees of pathogenicity (virulence), which play a role in the development and severity of infection.
Bacteria that adhere to the epithelium of the urinary tract are associated with colonization and infection
The mechanism of adhesion of gram-negative bacteria, particularly E. coli, is related to bacterial fimbriae that are rigid, hair-like appendages of the cell wall
These
fimbriae adhere to specific glycolipid components on epithelial cells
The most common type of fimbriae is type 1, which binds to mannose residues present in glycoproteins
Pathophysiology
Cont.
…
Glycosaminoglycan and Tamm-
Horsfall
protein are rich in mannose residues that readily trap those organisms that contain type 1 fimbriae, which are then washed out of the bladder.
Other fimbriae are mannose resistant and are associated more frequently with pyelonephritis, such as P fimbriae, which bind avidly to specific glycolipid receptors on
uroepithelial
cells
These bacteria are resistant to washout or removal by glycosaminoglycan and are able to multiply and invade tissue, and causing infection
Clinical Presentation of UTIs
Signs and symptoms
Lower UTI: dysuria, urgency, frequency,
nocturia
, suprapubic heaviness
Gross hematuria
Upper UTI: flank pain, fever, nausea, vomiting,
malaise
Physical examination
Upper UTI: costovertebral
tenderness
Clinical
Presentation of
UTIs
Cont
…
Laboratory tests
Bacteriuria
Pyuria (white blood cell count >10/mm 3 )
Nitrite-positive urine (with nitrite reducers)
Leukocyte esterase-positive urine
Antibody-coated bacteria (upper UTI
)
Diagnosis of UTIs
Symptoms alone are unreliable for the diagnosis of bacterial UTIs.
The key to the diagnosis of UTI is the ability to demonstrate significant numbers of microorganisms in an appropriate urine specimen to distinguish contamination from infection.
Diagnosis of
UTIs Cont.…
Urine testing
The gold standard for a urine test is to perform a bacteriological urine culture, with identification of the pathogen, with quantification and sensitivity testing.
To test whether the patient has a UTI at all, orientating indirect methods are often used in practice to detect the bacteria or inflammation (dip sticks).
The bacterial count may be assessed by urine microscopy and immersion culture media.
Midstream urine is normally collected
Diagnosis of
UTIs Cont.…
Dip sticks
Urine dip sticks are one of the most frequently used instruments for diagnostic testing if there is clinical evidence that a patient is suffering from UTI.
Multistix
are most often used, which may be able to detect nitrite (a metabolic product of typical pathogens of the urinary tract), leukocyte esterase, protein and blood (as a marker of inflammation
).
Diagnosis of UTIs Cont.…
Dip
sticks……
If
nitrite is detected, this increases the probability of a urinary tract infection, with a likelihood ratio [LR] of 2.6 to 10.6.
However, the sensitivity is relatively low.
In contrast, the detection of leukocyte esterase increases the probability to a lesser degree (LR 1.0 to 2.6). The detection of blood is admittedly highly sensitive, but the specificity is low.
Activity
: Small Group Discussion
What
is the treatment of
UTI
?
Pharmacological Treatment of UTIs
The management of a patient with a UTI includes;
Initial evaluation,
Selection of an antibacterial agent and duration of therapy, and
Follow-up
evaluation.
The initial selection of an antimicrobial agent for the treatment of UTI is based primarily on;
The severity of the presenting signs and symptoms,
The site of infection, and
Whether the infection is determined to be uncomplicated or complicated.
Other considerations include antibiotic susceptibility, side-effect potential, cost, and the comparative inconvenience of different
therapies
.
Empirical
Treatment of UTIs
Treatment
of UTI according to Pathogen
Monitoring of UTI Therapy
In asymptomatic post-treatment patients routine urinalysis and/or urine culture is not recommended
In patients with persistent symptoms, microbiological screening is recommended.
In women whose symptoms do not resolve by end of treatment, and in those whose symptoms resolve but recur within two weeks, urine culture and antimicrobial susceptibility testing should be performed
For therapy in this situation, one should assume that the infecting organism is not susceptible to the agent originally used.
Retreatment with a seven day regimen using another agent should be considered
Antibiotic treatments may be repeated with a more prolonged course, higher dosage and/or different compounds for patients with recurrent
infections
Key Points
UTI
is defined as the presence of microorganisms in the urinary tract that cannot be accounted for by contamination.
UTIs are classified by lower and upper urinary tract infections.
The most common cause of UTIs is
Escherichia coli
, which accounts for 80% to 90% of community-acquired
infections
Signs and Symptoms of UTI include
dysuria, urgency, frequency,
nocturia
, suprapubic heaviness
Variety of antibiotics can be used for the treatment of UTI
Evaluation
What
is UTIs?
What is the pathophysiology of
UTIs?
What are the signs and symptoms of uncomplicated UTI?
How is the treatment of Uncomplicated UTI?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 19: Pharmacotherapy of Folliculitis,
Furunculosis
and
Carbuncles
Learning Objectives
By the end of this session students are expected to be able to:
Define folliculitis,
furunculosis
and carbuncles
Explain pathophysiology of folliculitis,
furunculosis
and carbuncles
Explain the clinical presentation of folliculitis,
furunculosis
and carbuncles
Outline diagnosis of folliculitis,
furunculosis
and carbuncles
Describe pharmacological treatment of folliculitis,
furunculosis
and carbuncles
Describe the monitoring of folliculitis,
furunculosis
and carbuncles
therapy
Activity: Buzzing
What are Folliculitis, Furunculosis and Carbuncles?
Definition of Folliculitis, Furunculosis and Carbuncles
Folliculitis
, Furunculosis and Carbuncles
Folliculitis is inflammation of the hair follicle and is caused by physical injury, chemical irritation, or infection.
Infection occurring at the base of the eyelid is referred to as a stye.
Folliculitis is a superficial infection with pus present only in the dermis
,
Furuncles and carbuncles occur when a follicular infection extends from around the hair shaft to involve deeper areas of the skin.
A furuncle, commonly known as an
abscess
or
boil,
is a walled-off mass of purulent material arising from a hair follicle.
Definition of Folliculitis, Furunculosis and Carbuncles
The lesions are called
carbuncles
when they coalesce and extend to the
subcutaneous tissue
.
This aggregate of infected hair follicles forms deep masses that generally open and drain through multiple sinus tracts.
S. aureus
is the most common cause of folliculitis, furuncles, and carbuncles.
Inadequate chlorine levels in whirlpools, hot tubs, and swimming pools have been responsible for outbreaks of folliculitis caused by
P. aeruginosa
.
Pathophysiology of Folliculitis, Furunculosis and Carbuncles
The skin and subcutaneous tissues normally are extremely resistant to infection but may become susceptible under certain conditions.
Even when high concentrations of bacteria are applied topically or injected into the soft tissue, resulting infections are rare.
Several host factors act together to confer protection against skin infections.
Because the surface of the skin is relatively dry and has a pH of approximately 5.6, it is not conducive to bacterial growth.
Continuous renewal of the epidermal layer results in the shedding of
keratocytes
, as well as skin bacteria.
In addition, sebaceous secretions are hydrolyzed to form free fatty acids that strongly inhibit the growth of many bacteria and fungi.
Pathophysiology of Folliculitis, Furunculosis and Carbuncles
Conditions that may predispose a patient to the development of skin infections include
H
igh
concentrations of bacteria (>10 5 microorganisms),
E
xcessive
moisture of the skin,
I
nadequate
blood supply,
A
vailability
of bacterial nutrients, and
Damage to the corneal layer allowing for bacterial penetration.
The majority of Skin and Soft Tissue Infections result from the disruption of normal host defenses by processes such as skin puncture, abrasion, or underlying diseases (e.g., diabetes).
The nature and severity of the infection depend on both the type of microorganism present and the site of
inoculation
Clinical presentation and diagnosis of Folliculitis, Furunculosis and Carbuncles
Folliculitis
Pruritic, erythematous papules typically appear within 48 hours (range: 6 to 72 hours) of exposure to large numbers of organisms.
Papules evolve into pustules that generally heal in several days.
Systemic signs such as fever and malaise are uncommon, although they have been reported in cases caused by
P. aeruginosa
Clinical presentation and diagnosis of Folliculitis, Furunculosis and Carbuncles Cont.…
Furuncles/
Furunculosis
Furuncles can occur anywhere on hairy skin but generally develop in areas subject to friction and perspiration.
Furuncles are discrete lesions, whether occurring as singular or multiple nodules.
The lesion starts as a firm, tender, red nodule that becomes painful and fluctuant.
Lesions often drain spontaneously.
Lesions caused by CA-MRSA often have necrotic centers characteristic of “spider bites.”
Culture of lesion for laboratory investigation to conform the
presence
and the type of the pathogen
Clinical presentation and diagnosis of Folliculitis, Furunculosis and
Carbuncles Cont.…
Carbuncles
Carbuncles are broad, swollen, erythematous, deep, and painful follicular masses.
Carbuncles commonly develop on the back of the neck and are more likely to occur in patients with diabetes.
Unlike folliculitis and furuncles, carbuncles are commonly associated with fever, chills, and malaise.
Bacteremia with secondary spread to other tissues is common
Culture of lesion for laboratory investigation to conform the
prensence
and the type of the pathogen
Activity
: Small Group Discussion
What is the treatment of Folliculitis, Furunculosis and Carbuncles?
Pharmacological treatment of Folliculitis, Furunculosis and Carbuncles
Treatment of folliculitis generally requires only local measures, such as warm moist compresses or topical therapy (e.g., clindamycin, erythromycin, mupirocin
,
or benzoyl peroxide).
Topical agents generally are applied two to four times daily for 7 days.
Small furuncles generally can be treated with moist heat, which promotes localization and drainage of pus.
Large and/or multiple furuncles and carbuncles require incision and drainage.
Systemic antibiotics are usually not necessary unless accompanied by fever or extensive cellulitis.
Treatment of more severe infections generally consists of a penicillinase-resistant penicillin (such as
dicloxacillin
) or a first-generation cephalosporin (such as cephalexin) for 5 to 10 days
Drug Treatment
Monitoring of Folliculitis , Furuncles and Carbuncles Therapy
Many follicular infections resolve spontaneously without medical or surgical intervention.
Lesions should be incised if they do not respond to a few days of moist heat and nonprescription topical agents.
Following drainage, most lesions begin to heal within several days without antimicrobial therapy.
Any patient who is unresponsive to several days of therapy with a penicillinase-resistant penicillin or first-generation cephalosporin should have a culture and
sensitivity
Performed
because of the increasing frequency of MRSA.
Key Points
Folliculitis
is inflammation of the hair follicle and is caused by physical injury, chemical irritation, or infection
Symptoms of Folliculitis include Pruritic, erythematous papules typically appear within 48 hours (range: 6 to 72 hours) of exposure to large numbers of organisms
Treatment of folliculitis generally requires only local measures, such as warm moist compresses or topical therapy
Evaluation
What
are Folliculitis, Furuncles and Carbuncles?
What is the pathophysiology of
Folliculitis, Furuncles and Carbuncles?
What are the signs and symptoms of Folliculitis, Furuncles and Carbuncles?
How is the treatment of Folliculitis, Furuncles and Carbuncles?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 20: Pharmacotherapy of Vulvovaginal Candidiasis
Learning Objectives
By the end of this session students are expected to be able to:
Define vulvovaginal candidiasis
Explain pathophysiology of vulvovaginal candidiasis
Explain the clinical presentation of vulvovaginal candidiasis
Outline diagnosis of vulvovaginal candidiasis
Describe pharmacological treatment of vulvovaginal candidiasis
Describe the monitoring of vulvovaginal candidiasis therapy
Activity: Buzzing
What is Vulvovaginal
Candidiasis ?
Definition of Vulvovaginal Candidiasis
Vulvovaginal Candidiasis
Vulvovaginal candidiasis
(VVC) refers to infections in individuals with or without symptoms who have positive vaginal cultures for
Candida
species.
Depending on episodic frequency, VVC can be classified as either;
Sporadic or
Recurrent.
This classification is essential to understanding the pathophysiology, as well as
the
pharmacotherapy of
VVC.
Definition of Vulvovaginal
Candidiasis Cont.…
VVC may also be classified as;
uncomplicated, which refers to sporadic infections that are susceptible to all forms of antifungal therapy regardless of the duration of treatment, or
Complicated, in which consideration of factors affecting the host, microorganism, and pharmacotherapy all have an essential role in successful treatment.
Complicated VVC includes recurrent VVC, severe disease, non–
Candida albicans
candidiasis, and host factors, including diabetes mellitus, immunosuppression,
and pregnancy
Pathophysiology of Vulvovaginal Candidiasis
Candida albicans
is the major pathogen responsible for VVC, accounting for 80% to 92% of symptomatic episodes.
The remainders are caused by non–
species, with
Candida
glabrata
dominating.
The number of cases of non–
candidiasis appears to be increasing, possibly related to the use of nonprescription vaginal antifungal preparations and short-course therapy and/ or the increased use of long-term maintenance therapy in preventing recurrent infections.
Candida
species can act as commensal members of the vaginal flora.
Asymptomatic colonization with
Candida
species has been found in 10% to 20% of women of reproductive age.
Pathophysiology of Vulvovaginal
Candidiasis
Cont
…
Candida
organisms are dimorphic;
blastospores
are believed to be responsible for colonization (transmission and spread), whereas
Germinated Candida forms are associated with tissue invasion and symptomatic infections.
To colonize the vagina,
Candida
species must be able to attach to the mucosa. The attachment process is complex.
Not only are
candidal
surface structures important for attachment, but appropriate receptors for attachment must be present in the epithelial tissue.
Pathophysiology of Vulvovaginal Candidiasis
Cont.…
Not all women have the same range of receptors, which may explain variation in colonization.
Changes in the host’s vaginal environment or response are necessary to induce a symptomatic infection.
Unfortunately, in most cases of symptomatic VVC, no precipitating factor can be identified
C
linical presentation of Vulvovaginal candidiasis
General
Often involves both the vulva and the
vagina
Symptoms
Intense vulvar itching, soreness, irritation, burning on urination, and
dyspareunia
Signs
Erythema,
fissuring (crack),
curdy “cheese”-like discharge, satellite lesions,
edema
Laboratory tests
Vaginal pH—normal, saline and 10% KOH microscopy—
blastospores
or
pseudohyphae
Other diagnostic tests
Candida
cultures not recommended unless classic signs and symptoms with normal vaginal pH and microscopy are inconclusive or recurrence is suspected
Activity
: Small Group Discussion
What is the treatment of Vulvovaginal
Candidiasis ?
Treatment of Uncomplicated
Vulvovaginal candidiasis
Pharmacological Treatment of Vulvovaginal Candidiasis
Complicated Vulvovaginal Candidiasis
Complicated VVC occurs in patients who are immunocompromised or have uncontrolled diabetes mellitus and pregnant.
These
individuals need
a more aggressive treatment plan.
Current recommendations are to lengthen therapy to 10 to 14 days regardless of the
route of
administration.
Therapeutic options include those listed in Table
however
, regimens should be continued for 10 to 14 days.
Pharmacological Treatment of Vulvovaginal Candidiasis
Cont.….
Antifungal-Resistant Vulvovaginal Candidiasis
Resistance to azole antifungals should be considered in individuals who have persistently positive yeast cultures and fail to respond to therapy despite adherence to prescribed regimens.
These infections can be treated with;
intravaginal
twice weekly.
Boric acid should not be administered orally, as it is
toxic.
OR
Pharmacological Treatment of Vulvovaginal Candidiasis Cont.….
Monitoring of Vulvovaginal Candidiasis Therapy
Efficacy of the antifungal agent is partly influenced by patient adherence to the medication regimen.
Patients must be counseled on proper administration and dosing
Safety end points include monitoring for occurrence of the relevant drug side effects and drug interactions
It is still prudent to monitor for hypersensitivity reactions and side effects
that
might
occur with any medication.
Monitoring of Vulvovaginal Candidiasis
Therapy Cont.…..
GI intolerance is more associated with the oral azoles.
Hepatotoxicity can occur when azole therapy is prolonged beyond 7 to 10 days or high doses are used.
Periodic monitoring of liver enzymes (alanine transaminase and aspartate amino-transferase) should be considered, especially if prolonged therapy (longer than 21 days) is anticipated.
Patients who are receiving IV amphotericin B require daily monitoring by the pharmacist.
Key Points
Vulvovaginal
candidiasis
(VVC) refers to infections in individuals with or without symptoms who have positive vaginal cultures for
Candida
species
Symptoms include intense vulvar itching, soreness, irritation, burning on urination, and dyspareunia
Azole antifungals and other topical antifungals are drug of choice for
culvovaginal
candidiasis
Evaluation
What
is Vulvovaginal Candidiasis?
What is the pathophysiology of
Vulvovaginal Candidiasis?
What are the signs and symptoms of Vulvovaginal Candidiasis?
How is the treatment of Vulvovaginal Candidiasis?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 21: Pharmacotherapy of Asthma
Learning Objectives
By the end of this session students are expected to be able to:
Define asthma
Explain pathophysiology of asthma
Explain the clinical presentation of asthma
Outline diagnosis asthma
Describe pharmacological treatment of asthma
Describe the monitoring of
asthma
Activity: Buzzing
What is
Asthma
?
Definition of Asthma
Asthma is a common, chronic respiratory disease
of the airways of the lung characterized by either the intermittent or persistent presence of highly variable degrees of airflow obstruction from airway wall inflammation and bronchial smooth muscle constriction.
People with asthma experience episodes of wheezing, breathlessness and chest tightness due to widespread narrowing of the airways.
The cause of
Asthma
is
unknown
but the risk if associated with genetics and
environmental
factors.
Genetic factors account for 60% to 80% of the susceptibility.
Asthma represents a complex genetic disorder in that the asthma phenotype is likely a result of polygenic inheritance or different combinations of genes
Definition of
Asthma Cont.…..
Environmental risk factors for the development of asthma include;
S
ocioeconomic
status,
F
amily
size,
E
xposure
to secondhand tobacco smoke in infancy and in utero,
A
llergen
exposure
U
rbanization
,
R
espiratory
syncytial virus infection, and
E
xposure
to common childhood infectious
agents
List of agents and events Triggering Asthma
Pathophysiology Of Asthma
The major characteristics of asthma include a variable degree of airflow obstruction (related to bronchospasm, edema, and mucus hypersecretion) and airways inflammation
To understand the pathogenetic mechanisms that underlies the many phenotypes of asthma, it is critical to identify factors that initiate, intensify, and modulate the inflammatory response of the airways and to determine how these processes produce the characteristic airway abnormalities
.
Pathophysiology Of Asthma
Cont
….
The immunohistopathologic features of asthma include inflammatory cell infiltration:
Neutrophils (especially in sudden-onset, fatal asthma exacerbations; occupational asthma, and patients who smoke)
Eosinophils
Lymphocytes
Mast cell activation
Epithelial cell injury
P
athophysiology
of Asthma cont.
…
Airway inflammation contributes to airway
hyper responsiveness,
airflow limitation, respiratory symptoms, and disease chronicity.
In some patients, persistent changes in airway structure occur, including sub-basement fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, and angiogenesis.
Gene-by-environment interactions are important to the expression of asthma.
Atopy, the genetic predisposition for the development of an immunoglobulin E (
IgE
)-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma
.
Viral respiratory infections are one of the most important causes of asthma exacerbation and may also contribute to the development of asthma
Clinical Presentation And Diagnosis Of Asthma
Clinical Presentation is divided into
Acute Asthma
Chronic
asthma
Acute asthma
General
An episode can progress over several days or hours (usual scenario) or progresses rapidly over 1 to 2 hours
.
Clinical Presentation And Diagnosis Of Asthma
Acute
asthma…..
Symptoms
The patient is anxious in acute distress and complains of severe dyspnea , shortness of breath, chest tightness, or burning and wheezing sound
The patient is only able to say a few words with each breath.
Symptoms are unresponsive to usual measures (
shortacting
inhaled
β
2 –agonist administration).
Clinical Presentation And Diagnosis Of
Asthma
Cont
…
Acute
asthma…..
Signs
Signs
include expiratory and inspiratory wheezing on auscultation (breath sounds may be diminished with very severe obstruction),
D
ry
hacking cough,
T
achypnea
,
T
achycardia
,
P
ale
or cyanotic skin,
Hyper inflated
chest with intercostal and supraclavicular retractions, and
Hypoxic seizures if very severe
Clinical Presentation And Diagnosis Of Asthma
Cont
…
Acute
asthma……
Laboratory
PEF(peak expiratory flow)
and/or
FEV(Forced expiratory volume 1)
less than 40% of normal predicted values.
Decreased arterial oxygen (
PaO
2 ), and O 2 saturations by pulse oximetry (
SaO
2 less than 90% on room air is severe).
Increased
arterial or capillary CO 2 if mild, but in the normal range or increased in moderate to severe obstruction
.
Clinical Presentation And Diagnosis Of Asthma
Cont
…
Acute
asthma…
Other
Diagnostic Tests
Blood gases to assess metabolic acidosis (lactic acidosis) in severe obstruction.
Complete blood count if there are signs of infection (fever and purulent sputum).
Serum electrolytes as therapy with
β
2 -agonist and corticosteroids can lower serum potassium, magnesium, and phosphate, and increase glucose.
Chest radiograph if signs of consolidation on auscultation
Clinical Presentation And Diagnosis Of Asthma
Cont
…
Chronic Asthma
General
Asthma is a disease of exacerbation and remission, so the patient may not have any signs or symptoms at the time of exam.
Symptoms
The patient may complain of episodes of dyspnea, chest tightness, coughing (particularly at night), wheezing, or a whistling sound when breathing.
These often occur in association with exercise, but also occur spontaneously or in association with known allergens
.
Clinical Presentation And Diagnosis Of Asthma
Cont
…
Chronic
Asthma….
Signs
Expiratory wheezing on auscultation, dry hacking cough, or signs of atopy (allergic rhinitis and/or eczema) may occur.
Laboratory
Spirometry demonstrates obstruction (reduced FEV 1 /FVC(forced vital capacity) with reversibility following inhaled
β
2 -agonist administration (at least a 12% improvement in FEV 1).
Clinical Presentation And Diagnosis Of Asthma
Cont
…
Chronic
Asthma…..
Other
Diagnostic Tests
A
fall in FEV 1 of at least 15% following 6 minutes of near maximal exercise.
Elevated eosinophil count and
IgE
concentration in blood.
).
Activity
: Small Group Discussion
What is the treatment of
Asthma ?
Pharmacological Treatment of Asthma
Acute Severe Asthma
The primary goal is prevention of life-threatening asthma by early recognition of signs of deterioration and early intervention.
The principal goals of treatment include:
Correction of significant
hypoxemia ( A low level of oxygen in the blood)
Rapid reversal of airflow obstruction
Reduction of the likelihood of relapse of the exacerbation or future recurrence of severe airflow obstruction
Treatment of asthma according to severity
Pharmacological Treatment of
Asthma Cont..
Chronic Asthma in Adults
The assessment of the frequency of daytime and nighttime symptoms and limitation of physical activity determines whether asthma is intermittent or persistent.
There are 4 categories.
Therapy is step-wise (Step 1–4) based on the category of asthma and consists of:
Preventing the inflammation leading to bronchospasm (controllers)
Relieving bronchospasm (relievers)
Controller medicines in asthma
Inhaled corticosteroids e.g. Beclomethasone
Reliever medicines in asthma
Treatment
of Chronic Asthma According to
Severity
Monitoring Of Asthma Therapy
Lung function, either
spirometry
or peak flow measurements, should be monitored 5 to 10 minutes after each treatment.
Oxygen saturations can be easily monitored continuously with pulse oximetry.
For young children and infants, pulse oximetry, lung auscultation, and observation of the presence of supraclavicular retractions are useful.
The majority of patients will respond within the first hour of initial inhaled
β
2 -agonists regardless of history of home administration of drug.
Patients not achieving an initial response should be monitored every half hour to 1 hour.
Depending on whether there is a standard ED or a special unit for acute severe asthma, the decision to admit to the hospital should be made within 4 to 6 hours of entry to the emergency
department
Key Points
Asthma
is a common, chronic respiratory disease
of the airways of the lung characterized by either the intermittent or persistent presence of highly variable degrees of airflow obstruction from airway wall inflammation and bronchial smooth muscle constriction.
Symptoms of Asthma include
severe dyspnea, shortness of breath, chest tightness, or burning and wheezing sound
The principal goals of treatment of Asthma include correction of significant hypoxemia
and rapid reversal of airflow obstruction by using pharmacological and non pharmacological therapy
Evaluation
What
is Asthma?
What is the pathophysiology of
Asthma?
What are the signs and symptoms of Asthma?
How is the treatment of asthma?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 22: Pharmacotherapy of Diabetes Mellitus
Learning Objectives
By the end of this session students are expected to be able to:
Define diabetes mellitus
Explain pathophysiology of diabetes mellitus
Explain the clinical presentation of diabetes mellitus
Outline diagnosis of diabetes mellitus
Describe pharmacological treatment of diabetes mellitus
Describe the monitoring of diabetes mellitus therapy
Activity: Buzzing
What is Diabetes
Mellitus ?
Definition of Diabetes Mellitus
Diabetes mellitus (DM) is a group of metabolic disorders of fat, carbohydrate, and protein metabolism characterized by hyperglycemia
that results from defects in insulin secretion, insulin action (sensitivity), or both.
Or
Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, or by the ineffectiveness of the insulin produced which results in increased concentrations of glucose in the blood, which in turn damage many of the body's systems, in particular the blood vessels and nerves.
Definition of Diabetes Mellitus
Cont.…..
There are two types of DM
Type 1
diabetes (formerly known as insulin-dependent) in which the pancreas fails to produce the insulin which is essential for survival. This form develops most frequently in children and adolescents, but is being increasingly noted later in life.
Type 2
diabetes (formerly named non-insulin-dependent) which results from the body's inability to respond properly to the action of insulin produced by the pancreas.
Definition of Diabetes Mellitus Cont.…..
Type 2 diabetes is much more common and accounts for around 90% of all diabetes cases worldwide.
It occurs most frequently in adults, but is being noted increasingly in adolescents as well.
Certain genetic markers have been shown to increase the risk of developing Type 1 diabetes.
Type 2 diabetes is strongly familial, but it is only recently that some genes have been consistently associated with increased risk for Type 2 diabetes in certain populations.
Definition of Diabetes Mellitus Cont.…..
Both types of diabetes are complex diseases caused by mutations in more than one gene, as well as by environmental factors.
DM if not well managed can result into complications including;
Microvascular complications such as retinopathy, neuropathy, and nephropathy
Macrovascular
complications such as coronary heart disease, stroke, and peripheral vascular disease.
Definition of Diabetes Mellitus Cont.…..
Gestational Diabetes
It is a condition in which a woman without
diabetes
develops
high
blood sugar
levels
during
pregnancy
Diabetes in pregnancy may give rise to several adverse outcomes, including congenital malformations, increased birth weight and an elevated risk of perinatal mortality.
Strict metabolic control may reduce these risks to the level of those of non-diabetic expectant mothers
Pathophysiology Of Diabetes Mellitus
Type 1 DM
Type 1 DM is the result of a combination of genetic and environmental influences.
Type 1 DM is characterized by an absolute deficiency of pancreatic
β
-cell function.
Most often this is the result of an
immune mediated
destruction of pancreatic
β
cells, but rare unknown or idiopathic processes may contribute.
It most commonly results from autoimmune destruction of insulin-producing β-cells in the pancreas.
Pathophysiology Of Diabetes Mellitus Cont.….
One or more environmental factors, such as enteroviruses, dietary factors or toxins, might trigger the development of T-cell dependent autoimmunity in genetically susceptible individuals
Autoimmunity is manifested by detectable antibodies to ICA512/IA-2, insulin autoantibody (IAA) and glutamic acid decarboxylase (GAD).
Insulitis with gradual β-cell destruction leads to pre-diabetes and finally to overt DM.
Pathophysiology Of Diabetes Mellitus Cont.….
Type 2 DM
Type 2 diabetic individuals are characterized by
defects in insulin secretion; and
Insulin resistance involving muscle, liver, and the adipocyte.
Impaired insulin secretion
Impaired insulin secretion is a decrease in glucose responsiveness, which is observed before the clinical onset of disease.
More specifically, impaired glucose tolerance (IGT) is induced by a decrease in glucose-responsive early-phase insulin secretion, and a decrease in additional insulin secretion after meals causes postprandial
hyperglycaemia
Pathophysiology Of Diabetes Mellitus Cont.….
In the type 2 diabetic patient, decreased postprandial insulin secretion is due to both impaired pancreatic beta cell function and a reduced stimulus for insulin secretion from gut
hormones
Normally
there is an increased insulin secretion in response to an oral glucose stimulus and which is referred to as “the incretin effect”
The incretin effect is the result that gut-derived hormones (,glucagon-like peptide 1 (GLP-1) and glucose-dependent
insulinotropic
polypeptide (GIP)) when stimulated by glucose.
In type 2 diabetic patients, this “incretin effect” is very minimal
Pathophysiology Of Diabetes Mellitus Cont.….
The two gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP), are responsible for over 90% of the increased insulin secretion seen in response to an oral glucose load.
Patients with type 2 diabetes remain sensitive to GLP-1 while they are often resistant to GIP.
Pathophysiology Of Diabetes Mellitus Cont.….
Insulin resistance
Insulin resistance is a condition in which insulin in the body does not exert sufficient action proportional to its blood concentration.
The impairment of insulin action in major target organs such as liver and muscles is a common pathophysiological feature of type 2 diabetes.
Insulin resistance develops and expands prior to disease onset.
Pathophysiology Of Diabetes Mellitus Cont.….
Insulin resistance is related to genetic factors and environmental factors (hyperglycaemia, free fatty acids, inflammatory mechanism, etc.).
Known genetic factors, such as change in the shape of insulin receptors that directly affect insulin signalling mechanisms is associated with visceral obesity and promote insulin resistance.
Glucolipotoxicity and inflammatory mediators are also important as the mechanisms for impaired insulin secretion and insulin signalling impairment
Clinical Presentation Of Diabetes Mellitus
The clinical presentations of type 1 DM and type 2 DM are very different.
Autoimmune type 1 DM can occur at any age.
Individuals with type 1 DM are often thin and are prone to develop diabetic ketoacidosis if insulin is withheld, or under conditions of severe
stress;-
P
olyuria,(Excessive urination)
P
olydipsia
,
(Excessive thirst)
P
olyphagia (Excessive eating)
Weight loss.
Blurred vision
Slow-healing sores
Frequent infections
Clinical Presentation Of Diabetes Mellitus
Signs And Symptoms Of Type 2
Diabetes
Patients
with type 2 DM often present without symptoms,
Even though complications tell us that they may have been hyperglycemic
For several years.
Often these patients are diagnosed secondary to unrelated blood testing.
Lethargy,
polyuria,
nocturnal,
and
polydipsia
Blurred vision
Slow-healing sores
Frequent infections
Patients can have normal to grossly abnormal insulin
sensitivity.
Clinical Presentation of DM
Diagnosis Of Diabetes Mellitus
DM is diagnosed by both
clinical using
signs and symptoms together with blood tests
The following are blood test for diagnosis of
DM
Glycated hemoglobin (A1C) test.
This blood test, which doesn't require fasting, indicates your average blood sugar level for the past two to three months.
It measures the percentage of blood sugar attached to hemoglobin, the oxygen-carrying protein in red blood cells.
An A1C level of 6.5 percent or higher on two separate tests indicates DM.
An A1C between 5.7 and 6.4 percent indicates prediabetes.
Below 5.7 is considered normal
.
Diagnosis Of Diabetes
Mellitus
Cont
….
Random blood glucose test.
A blood sample will be taken at a random time.
Normal blood glucose is 11
millimoles
Reading of 11.1
millimoles
per liter (
mmol
.
Fasting blood glucose test.
A blood sample will be taken after an overnight fast.
A fasting blood glucose level less than 5.6
mmol
A fasting blood glucose level from 5.6 to 6.9
mmol
A fasting blood glucose of 7
mmol
Diagnosis Of Diabetes
Mellitus
Cont
….
Oral glucose tolerance test.
For this test, fasting blood glucose level is measured after overnight fast.
Then a patient drink sugary liquid and blood glucose levels are measured periodically for the next two hours.
A blood sugar level less
than
7.8
mmol
More than 11.1
mmol
A reading between 7.8
mmol
mmol
.
Urinalysis
If type
1 diabetes
is suspected, Urinalysis will be done to investigate for the presence of ketones bodies
Diagnostic criteria for DM
Activity
: Small Group Discussion
What
is the treatment of Diabetes
Mellitus
?
Pharmacological Treatment Of Diabetes Mellitus
The primary goals of DM management are to;
reduce the risk for microvascular and macrovascular disease complications,
ameliorate symptoms,
reduce mortality,
Improve quality of life.
Near-normal
glycaemia
will reduce the risk for development of microvascular disease complications,
Pharmacological Treatment Of Diabetes
Mellitus
Cont
…
Aggressive management of traditional cardiovascular risk factors (i.e., smoking cessation, treatment of dyslipidemia, intensive blood pressure control, and antiplatelet therapy) are needed to reduce the likelihood of development of
macrovascular
disease.
Pharmacological treatment of DM depends on the type and the severity of the disease
Insulin are the mainstay for treatment of type 1 DM
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Treatment of Type 2
DM
Oral
Antihyperglycemic Drugs
Biguanide
:
Metformin
Metformin is considered the agent of first line for treatment of T2DM, in the absence of contraindications
It decreases fasting blood glucose by approximately 20% and HbA1c by 1.5%.
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Treatment of Type 2 DM
Oral Antihyperglycemic
Drugs…..
It
can be given in combination with sulfonylureas,
Glinides
, alpha-glucosidase inhibitors, insulin, thiazolidinedione (TZD), glucagon-like peptide-1 receptor agonist (RA-GLP1), dipeptidyl peptidase 4 inhibitors (iDPP4), and sodium-glucose co-transporter 2 inhibitors (iSGLT2).
Metformin
is contraindicated in patients with factors that predispose to lactic acidosis.
The predisposing factors are: A renal function damaged, concomitant liver disease or excessive alcohol intake, unstable or acute heart failure and personal history of lactic
acidosis
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic
drugs
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic drugs
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic drugs
Pharmacological Treatment Of Diabetes Mellitus
Cont
…
Antihyperglycemic drugs
Monitoring of Diabetes Mellitus Therapy
A comprehensive pharmaceutical care plan for the patient with DM is needed in order to reach treatment goals
Parameters
to monitor include
Glycemic control (tested minimally yearly; HbA
lc
<8% is good control and
HbA
lc
>9% is poor control),
Minimally, HbA
lc
should be measured twice a year in patients meeting treatment goals on a stable therapeutic regimen.
Quarterly assessments are recommended for those whose therapy has changed or who are not meeting glycemic goals.
Glycemic control requires frequent assessment and adjustment in diet, exercise, and pharmacologic
therapies
Monitoring of Diabetes Mellitus
Therapy Cont.….
L
dL
)
Fasting lipid profiles should be obtained as part of an initial assessment and thereafter at each
Follow-up visit, annually, or every 2 years if the lipid profile suggests low risk.
Documenting
regular frequency of foot exams (each visit), urine albumin assessment
(annually), dilated ophthalmologic exams (yearly or more frequently with identified abnormalities), and office visits for follow-up are also important.
Management of other cardiovascular risks (e.g., smoking and antiplatelet therapy) are components of preventive medicine strategies
Key
Points
Diabetes
mellitus (DM) is a group of metabolic disorders of fat, carbohydrate, and protein metabolism
characterized by hyperglycemia
that results from defects in insulin secretion, insulin action (sensitivity), or both
Symptoms of Diabetes Mellitus are variable and depends on the type of the disease
wheather
is type 1 or 2 DM.
Insulin is the mainstay pharmacological treatment for type 1 DM while Metformin is first line pharmacological treatment for type 2 DM obese patient
Evaluation
What
is Diabetes Mellitus?
What is the pathophysiology of Diabetes Mellitus?
What are the signs and symptoms of Diabetes Mellitus?
How is the treatment of Diabetes Mellitus?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 23: Pharmacotherapy of Peptic Ulcers Disease
Learning Objective
By the end of this session students are expected to be able to:
Define peptic ulcers disease
Explain pathophysiology of peptic ulcers disease
Explain the clinical presentation of peptic ulcers disease
Outline diagnosis of peptic ulcers disease
Describe pharmacological treatment of peptic ulcers disease
Describe the monitoring of peptic ulcers disease
therapy
Activity: Buzzing
What is Peptic ulcer Disease?
Definition of Peptic Ulcers Disease
Peptic
ulcer disease refers to painful sores or ulcers in the lining of the stomach or first part of the small intestine, called the duodenum.
Peptic ulcer disease (PUD), also known as a peptic ulcer or stomach ulcer, is a break in the lining of the stomach, first part of the small intestine, or occasionally the lower
oesophagus
An ulcer in the stomach is known as a
gastric ulcer
while that in the first part of the intestines is known as a
duodenal ulcer
.
Most ulcers are caused by an infection with a type of bacteria called
Helicobacter pylori
(H. pylori).
Definition of Peptic Ulcers
Disease Cont..
Factors that can increase your risk for ulcers include:
Use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as;
Aspirin, even safety-coated aspirin and aspirin in powered form can frequently cause ulcers.
naproxen,
ibuprofen
Definition of Peptic Ulcers Disease Cont..
Many other prescription drugs such;
Concomitant use of oral bisphosphonates (e.g., alendronate)
Concomitant use of corticosteroids
Concomitant use of anticoagulant or coagulopathy
Concomitant use of antiplatelet drugs (e.g.,
clopidogrel
)
Concomitant use of selective serotonin reuptake inhibitor
Definition of Peptic Ulcers Disease Cont..
Excess
acid production from
Zollinger
-Ellison syndrome, (ZES)
gastrinomas
,
tumors
of the acid producing cells of the stomach that increases acid output
Excessive drinking of alcohol
Smoking or chewing tobacco
Peptic ulcers are also associated with radiation, chemotherapy, vascular insufficiency, and other chronic
diseases
Pathophysiology of Peptic Ulcers Disease
A physiologic imbalance between aggressive (gastric acid and pepsin) and protective factors (mucosal defense and repair) remain important issues in the pathophysiology of gastric and
duodenal ulcers.
Gastric acid is secreted by the parietal cells, which contain receptors for histamine, gastrin, and acetylcholine.
Acid (as well as
H. pylori
infection and NSAID use) is an independent factor that contributes to the disruption of mucosal integrity.
Increased acid secretion has been observed for patients with duodenal with Zollinger-Ellison syndrome (ZES) (described in the
section
Pathophysiology of Peptic Ulcers
Disease Cont..
Zollinger-Ellison Syndrome) have profound gastric acid hypersecretion resulting from a gastrin-producing tumor
H. pylori
produce large amounts of urease, which hydrolyzes urea in the gastric juice and converts it to ammonia and carbon dioxide.
The local buffering effect of ammonia creates a neutral microenvironment within and surrounding the bacterium, which protects it from the lethal effect of gastric acid
.
H. pylori
also produces acid inhibitory proteins, which allows it to adapt to the low-pH environment of the stomach
Pathophysiology of Peptic Ulcers Disease Cont..
Mucosal
injury is produced by
elaborating bacterial enzymes (urease, lipases, and proteases),
Lipases and proteases degrade gastric mucus, ammonia produced by urease may be toxic to gastric epithelial cells,
Adherence
bacterial adherence enhances the uptake of toxins into gastric epithelial cells
H. pylori virulence factors.
H. pylori
induces gastric inflammation by altering the host inflammatory response and damaging epithelial cells directly by cell-mediated immune mechanisms or indirectly by activated neutrophils or macrophages attempting to phagocytose bacteria or bacterial products
Clinical presentation and Diagnosis of Peptic ulcers disease
The clinical presentation of PUD varies depending on the severity of epigastric pain and the presence of complications
Ulcer-related pain in duodenal ulcer often occurs 1 to 3 hours after meals and is usually relieved by food, but this is
variable
General
Mild epigastric pain or acute life-threatening upper gastrointestinal
complications
Clinical presentation and Diagnosis of Peptic ulcers
disease
Cont
….
Symptoms
Abdominal
pain that is often epigastric and described as burning but may present as vague discomfort, abdominal fullness, or cramping
A typical nocturnal pain that awakens the patient from sleep (especially between 12 AM and 3 AM)
The severity of ulcer pain varies from patient to patient and may be seasonal,
episodes of discomfort usually occur in clusters, lasting up to a few weeks and followed by a pain-free period or remission lasting from weeks to years
Clinical presentation and Diagnosis of Peptic ulcers disease
Cont
….
Symptoms…..
Changes
in the character of the pain may suggest the presence of complications
Heartburn, belching, and bloating often accompany the pain
Nausea, vomiting, and anorexia are more common for patients with gastric ulcer than with duodenal ulcer but may also be signs of an ulcer-related complication
Clinical presentation and Diagnosis of Peptic ulcers disease
Cont
….
Signs
Weight loss associated with nausea, vomiting, and anorexia
Complications including ulcer bleeding, perforation, penetration, or
obstruction
Laboratory tests
Gastric acid secretory studies
The
hematocrit
and
hemoglobin
are low with bleeding, and stool
hemoccult
tests are positive.
Tests for
Helicobacter pylori
.
Clinical presentation and Diagnosis of Peptic ulcers disease
Cont
….
Diagnostic tests
Fiberoptic
upper endoscopy (esophagogastroduodenoscopy) detects more than 90% of peptic ulcers and permits direct inspection, biopsy, visualization of superficial erosions, and sites of active bleeding.
Upper gastrointestinal radiography with barium and upper endoscopy are also the diagnostic procedures for suspected peptic ulcer.
Tests for Detection of Helicobacter
Pyroli
Activity
: Small Group Discussion
What is the treatment of Peptic Ulcers Disease
?
Pharmacological Treatment of Peptic Disease
The treatment of chronic PUD varies depending on the etiology of the ulcer (
H. pylori
or NSAID), whether the ulcer is initial or recurrent, and whether complications have occurred
Overall treatment is aimed at relieving ulcer pain, healing the ulcer, preventing ulcer recurrence, and reducing ulcer-related complications.
The goal of therapy for
H. pylori
positive patients with an active ulcer, a previously documented ulcer, or a history of an ulcer-related complication, is to eradicate
H. pylori,
heal the ulcer, and cure the disease.
Successful eradication heals ulcers and reduces the risk of recurrence for most patients
.
Drug Regimens Used to Eradicate Helicobacter pylori
Pharmacological Treatment of Peptic
Disease Cont..
Other options for Triple therapy for eradication of the H. pylori include;
Omeprazole (PO) 20mg twice daily Plus
Amoxycillin
(PO) 1000mg twice daily
AND
Metronidazole
(PO) 400mg twice daily for 10–14 days
OR
Lansoprazole (PO) 30mg twice daily
AND
Clarithromycin
(PO) 500mg twice
AND
Tinidazole (PO) 500mg twice daily for 10–14 days
OR
Any combination of PPI + 2 antibiotics active for
H. pylori
Other
drugs as indicated in the table below can also be used in the treatment of peptic ulcer
disease
Oral Drug Regimen Used To Heal Peptic Ulcer And Maintain Ulcer Healing
Monitoring of Peptic Ulcers Disease Therapy
Treatment of
Helicobacter pylori
-associated ulcer
Assess patient allergies to determine if allergic to penicillin (or other antibiotics) so that drug regimens that contain penicillin (or other antibiotics) can be avoided.
Assess patient use of alcohol or alcohol-containing products with metronidazole and oral birth control medications with antibiotics and counsel appropriately.
Assess likelihood of nonadherence to the drug regimen as a cause of treatment failure.
Recommend a different antibiotic combination if
H . pylori
eradication fails
.
Monitoring of Peptic Ulcers Disease
Therapy Cont.…
Inform the patient of change in stool color when bismuth salicylate is included in an
H. pylori
eradication regimen.
Assess and monitor patients for potential adverse effects, especially those associated with metronidazole, clarithromycin, and amoxicillin.
Assess and monitor patients for potential drug interactions, especially those receiving metronidazole, clarithromycin, or cimetidine.
Monitor patients for persistent or recurrent symptoms within 14 days after completion of a course of
H. pylori
eradication therapy.
Monitoring of Peptic Ulcers Disease
Therapy Cont.….
Provide
patient education to patients who are receiving
H . pylori
eradication therapy and include why antibiotic and antiulcer combinations are used;
when and how to take medications;
adverse effects;
alarm symptoms;
the importance of adherence to the entire course of drug treatment; and
Contact their healthcare provider if alarm symptoms develop (e.g., blood in the stools, black tarry stools, vomiting, severe abdominal pain), or if symptoms persist or return after H. pylori eradication
.
Monitoring of Peptic Ulcers Disease Therapy
Treatment of NSAIDS induced ulcers
Monitor
patients for signs and symptoms of NSAID-related upper GI complications.
Assess and monitor patients for potential drug interactions and adverse effects (especially misoprostol).
Provide patient education to patients who are at risk of NSAID-induced ulcers or GI-related complications and include why
co-therapy
is used with nonselective NSAIDs;
when and how to take medications;
adverse effects;
alarm symptoms;
when to contact their healthcare provider; and
The importance of adherence to drug treatment
.
Key
Points
Peptic
ulcer disease refers to painful sores or ulcers in the lining of the stomach or first part of the small intestine, called the duodenum
A physiologic imbalance between aggressive (gastric acid and pepsin) and protective factors (mucosal defense and repair) and
H. pylori
infection remain important issues in the pathophysiology of gastric and duodenal ulcers.
Symptoms of PUD include abdominal pain that is often epigastric and described as burning but may present as vague discomfort, abdominal fullness, or cramping
The treatment of chronic PUD varies depending on the etiology of the ulcer (
H. pylori
or NSAID), whether the ulcer is initial or recurrent, and whether complications have occurred
Evaluation
What
is Peptic Ulcers Disease?
What is the pathophysiology of
Peptic Ulcers Disease
?
What are the signs and symptoms of Peptic Ulcers Disease?
How is the treatment of Peptic Ulcers Disease?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 24: Pharmacotherapy of Hypertension
Learning Objective
By the end of this session students are expected to be able to:
Define hypertension
Explain pathophysiology of hypertension
Explain the clinical presentation of hypertension
Outline diagnosis of hypertension
Describe pharmacological treatment of hypertension
Describe the monitoring of hypertension therapy
Activity: Buzzing
What is
Hypertension
?
Definition of Hypertension
Hypertension is defined as a systolic blood pressure (SBP) of higher than 140mmHg or a diastolic blood pressure (DPB) higher than 90mmHg
The classification of BP is as been follows
:
Normal: Systolic lower than 120 mm Hg, diastolic lower than 80 mm Hg
Prehypertension: Systolic 120-139 mm Hg, diastolic 80-89 mm Hg
Stage 1: Systolic 140-159 mm Hg, diastolic 90-99 mm Hg
Stage 2: Systolic 160 mm
Hg or greater, diastolic 100 mm Hg or
greater
Definition of Hypertension
Cont.…..
Hypertension may be;
Primary, which may develop as a result of environmental or genetic causes, or
Secondary, which has multiple etiologies, including renal, vascular, and endocrine causes.
Primary or essential hypertension accounts for 90-95% of adult cases, and secondary hypertension accounts for 2-10% of cases.
Pathophysiology
of Hypertension
Multiple factors that control BP are potential contributing components in the development of essential hypertension.
These include;
Malfunctions in either humoral [i.e., the renin-angiotensin- aldosterone system (RAAS)] or vasodepressor mechanisms,
Abnormal neuronal mechanisms,
Defects in peripheral autoregulation, and
Disturbances in sodium, calcium, and natriuretic hormone.
Pathophysiology of Hypertension
Cont
…
Many of these factors are cumulatively affected by the multifaceted RAAS, which ultimately regulates arterial BP.
It is probable that no one factor is solely responsible for essential hypertension
.
Clinical
Presentation and Diagnosis of Hypertension
General:
The patient may appear healthy or may have the presence of additional CV risk factors:
Age (greater than or equal to 55 for men, greater than or equal to 65 for women)
Diabetes mellitus
Dyslipidemia
(elevated cholesterol or fats in the blood)
Microalbuminuria
Family history of premature CV disease
Physical inactivity
Tobacco
use
Clinical Presentation and Diagnosis of Hypertension
Cont
….
Symptoms:
Usually none related to elevated BP.
Signs:
Previous BP values in either the prehypertension or the hypertension category.
Laboratory Tests:
BUN/serum creatinine,
fasting lipid panel,
fasting blood glucose
,
Clinical Presentation and Diagnosis of Hypertension
Cont
….
Laboratory Tests….
serum
electrolytes (sodium, potassium),
Spot urine albumin-to-creatinine ratio.
The patient may have normal values and still have hypertension.
However, some may have abnormal values that are consistent with either additional CV risk factors or hypertension-related damage.
Other Diagnostic Tests:
12-lead electrocardiogram,
Estimated glomerular filtration rate [using modification of diet in renal disease (MDRD) equation].
Clinical Presentation and Diagnosis of Hypertension
Cont
….
Hypertension-Related
Target-Organ Damage:
The patient may have a previous medical history or diagnostic findings that indicate
the presence of hypertension-related target-organ damage:
Brain (stroke, transient ischemic attack, dementia)
Eyes (retinopathy)
Heart (left ventricular hypertrophy, angina, prior MI, prior coronary revascularization, heart failure)
Kidney (chronic kidney disease)
Peripheral vasculature (peripheral arterial disease)
Activity
: Small Group Discussion
What is the treatment of
Hypertension
?
Pharmacological Treatment Of Hypertension
The overall goal of treating hypertension is to reduce hypertension- associated morbidity and mortality.
. CV
events, cerebrovascular events, heart failure, and kidney disease).
Reducing CV risk remains the primary purpose of hypertension therapy and the specific choice of drug therapy is significantly influenced by evidence demonstrating such CV risk reduction.
Treating patients with hypertension to achieve a desired target BP value is simply a surrogate goal of therapy
Pharmacological Treatment Of
Hypertension
Cont
….
In most cases the target BP should be: systolic below 140 mmHg and diastolic below 90 mmHg.
In diabetic patients and patients with cardiac or renal impairment, target BP should be below 130/80mmHg;
The
choice of initial drug therapy depends on the degree of BP elevation and presence of compelling indications (
e.g
coexisting conditions such as diabetes and other cardiovascular conditions)
Most patients with stage 1 hypertension should be initially treated with a first-line antihypertensive drug, or the combination of two agents.
Combination drug therapy is recommended for patients with more severe BP elevation (stage 2 hypertension), using preferably two first-line antihypertensive drugs
.
Pharmacological Treatment Of Hypertension
Cont
….
Recommended Initial Medication Doses For Hypertension Treatment
Thiazide
diuretics
Hydrochlothiazide
12.5mg/daily
OR
Bendroflumethiazide
5mg/daily
OR
Indapamide
5mg/daily preferred for patient with previous stroke/TIA
Pharmacological Treatment Of Hypertension
Cont
….
Recommended Initial Medication Doses For Hypertension
Treatment…..
Loop
diuretics
Furosemide initial dose 40mg twice a day
OR
Torsemide
5mg/daily
Dose can be up scaled depending on congestive status to maximum dose
Pharmacological Treatment Of Hypertension
Cont
….
Recommended Initial Medication Doses For Hypertension
Treatment……
Mineralocorticoid
(Aldosterone) Receptor antagonist
Spironolactone 25mg/daily
OR
Eplerenone
25mg/daily
Angiotensin-Converting Enzyme Inhibitor (ACEI)
Captopril 6.125mg, 12.5mg or 25mg three times daily
OR
Enalapril
10mg twice a day
OR
Perindopril 8mg/daily orally
Pharmacological Treatment Of Hypertension
Cont
….
Angiotensin Receptor Blocker–ARB
(*Don’t combine with ACEI contraindications, indicated in patient sensitive to ACEIs)
Losartan 50mg/daily*
Beta–blocker
Atenolol 50mg/daily
OR
Metoprolol 50mg/daily
Pharmacological Treatment Of Hypertension
Cont
….
Calcium
Channel Blocker (
Dihydropyridines
):
Nifedipine
(Slow Release/Long Acting) 20mg/30mg/ 60mg/90mg/daily
OR
Amlodipine 5mg or 10mg/daily
Non–
dihydropyridine
Verapamil 30mg twice–three times a daily
OR
Diltiazem 30mg twice–three times a day
Monitoring of Hypertension Therapy
Routine ongoing monitoring to assess disease progression, the desired effects of antihypertensive
therapy
The
monitoring parameters include;
Signs
and symptoms of Disease Progression
Efficacy
of
antihypertensive
and BP goal attainment, and
Undesired
adverse side effects (toxicity)
Monitoring of Hypertension
Therapy
Cont
…
Disease Progression
Patients should be monitored for signs and symptoms of progressive hypertension-associated target-organ disease.
A careful history for ischemic chest pain (or pressure), palpitations, dizziness, dyspnea, orthopnea, headache, sudden change in vision, one-sided weakness, slurred speech, and loss of balance should be taken to assess the presence of CV and cerebrovascular hypertensive complications
Monitoring of Hypertension
Therapy
Cont
…
E
fficacy
The most important strategy to prevent CV morbidity and mortality in hypertension is BP control to goal values
Clinic-based BP monitoring remains the standard for managing hypertension.
BP response should be evaluated 2 to 4 weeks after initiating or making changes in therapy.
Once goal BP values are attained, assuming no signs or symptoms of acute target-organ
disease are present, BP monitoring can be done every 3 to 6 months.
More frequent evaluations are required for patients with a history of poor control, nonadherence, progressive target-organ damage, or symptoms of adverse drug effects.
Self-measurements of BP or automated ambulatory BP monitoring can be useful clinically to establish effective 24-hour
control
Monitoring of Hypertension
Therapy
Cont
…
Toxicity
Patients should be monitored routinely for symptoms of adverse drug reactions.
Laboratory monitoring should typically occur 2 to 4 weeks after starting a new agent or dose increase, and then every 6 to 12 months in stable patients.
Key
Points
Hypertension
is defined as a systolic blood pressure (SBP) of higher than 140mmHg or a diastolic blood pressure (DPB) higher than 90mmHg
The overall goal of treating hypertension is to reduce hypertension- associated morbidity and mortality.
This morbidity and mortality is related to hypertension-associated target-organ damage
The choice of initial drug therapy depends on the degree of BP elevation and presence of compelling indications (
e.g
coexisting conditions such as diabetes and other cardiovascular conditions)
Evaluation
What
is Hypertension?
What is the pathophysiology of
Hypertension?
What are the signs and symptoms of Hypertension?
How is the treatment of Hypertension?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 25: Pharmacotherapy of Heart Failure
Learning Objectives
By the end of this session students are expected to be able to:
Define heart failure
Explain pathophysiology of heart failure
Explain the clinical presentation of heart failure
Outline diagnosis of heart failure
Describe pharmacological treatment of heart failure
Describe the monitoring of heart failure therapy
Activity: Buzzing
What is Heart Failure?
Definition of Heart Failure
Heart failure is a progressive clinical syndrome that can result from any abnormality in cardiac structure or function that impairs the ability of the ventricle to fill with or eject blood, thus rendering the heart unable to pump blood at a rate sufficient to meet the metabolic demands of the body.
It is the final common pathway for numerous cardiac disorders, including those affecting the pericardium, heart valves, and myocardium.
Diseases that adversely affect ventricular diastole (filling), ventricular systol(Contraction), or both can lead to heart failure
Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress
Definition of Heart Failure Cont…
Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress
Heart failure can result from any disorder that affects the ability of the heart to contract (systolic function) and/or relax (diastolic dysfunction)
Therefore, Heart Failure can be;
Systolic Heart Failure or/and
Diastolic Heart Failure
Definition of Heart Failure Cont…
Heart failure with impaired systolic function (i.e., reduced LVEF) is the classic, more familiar form of the disorder
LVEF (Left ventricular ejection fraction
Common Cause Of Heart Failure
Pathophysiology of Heart Failure
Key components of the pathophysiology of cardiac remodeling are.
Myocardial injury (e.g., myocardial infarction) results in the activation of a number of hemodynamic and neurohormonal compensatory responses in an attempt to maintain circulatory homeostasis.
Chronic activation of the neurohormonal systems results in a cascade of events that affect the myocardium at the molecular and cellular levels.
These events lead to the changes in ventricular size, shape, structure, and function known as ventricular remodeling.
The alterations in ventricular function result in further deterioration in cardiac systolic and diastolic function, which further promotes the remodeling process. (LV left ventricular)
Pathophysiology of Heart Failure Cont….
Clinical presentation and diagnosis of HF
General
Patient presentation may range from asymptomatic to cardiogenic shock.
Symptoms
Dyspnea, (Shortness of breath)
Orthopnea (Discomfort when breathed)
Paroxysmal nocturnal dyspnea (an attack of severe shortness of breath and coughing that generally occur at night)
Exercise intolerance
Tachypnea (Fast breathing)
Clinical presentation and diagnosis of HF Cont…..
Symptoms…..
Cough
Fatigue (feeling overtired)
Nocturia (Frequent urination)
Hemoptysis (Coughing up blood)
Abdominal pain
Anorexia
Nausea
Bloating (Build up of gas in the stomach and intestine)
Poor appetite, early satiety
Ascites (Abnominal swelling)
Mental status changes
Clinical presentation and diagnosis of HF Cont…..
Signs
Pulmonary rales (Abnormal lung sound)
Pulmonary edema
Cool extremities
Pleural effusion (build up of fluids between the tissue that line the lungs and the chest)
Tachycardia (Fast heart rate)
Narrow pulse pressure
Clinical presentation and diagnosis of HF Cont…..
Signs…….
Cardiomegaly
Peripheral edema
Hepatojugular reflux (test for measuring jugular venous pressure through the distention of the internal jugular vein)
Hepatomegaly
Clinical presentation and diagnosis of HF Cont…..
Laboratory Tests
Electrocardiogram may be normal, or it could show numerous abnormalities, including acute ST-T wave changes from myocardial ischemia, atrial fibrillation, bradycardia, and left ventricular hypertrophy.
Serum creatinine may be increased due to hypo perfusion.
Preexisting renal dysfunction can contribute to volume overload.
Complete blood count (CBC) can be useful in determining if heart failure is due to a reduced oxygen-carrying capacity.
Clinical presentation and diagnosis of HF Cont…..
Laboratory Tests
…
Chest x-ray: useful for detecting cardiac enlargement, pulmonary edema, and pleural effusions
Echocardiogram: used to assess the size of the left ventricle, valve function, pericardial effusion, wall motion abnormalities, and ejection fraction
Activity: Small Group Discussion
What is the treatment of Heart Failure??
Pharmacological Treatment of Heart Failure
Treatment of Heart Failure of depends on the stage of the Disease
There are four identified stages of heart failure, and their treatment recommendations
Unless contraindicated, all patients with HF-REF(reduced ejection fraction) should be started on an ACE inhibitor and a beta blocker (and a diuretic, in most cases).
No patient should receive three drugs which block the renin-angiotensin-aldosterone system as hyperkalaemia and renal dysfunction will be common.
The safety and efficacy of combining an ACE inhibitor, an ARB and MRA is uncertain and the use of these three drugs together is not recommended
Functional Classification of Heart Failure
Treatment allogarism of Heart failure according to functional stage of Heart Failure
Pharmacological Treatment of Heart Failure Cont….
Beta Blockers
A meta-analysis confirms that beta blockers also reduce mortality in patients with diabetes and HF
All patients with heart failure with reduced ejection fraction,class II-IV, should be started on beta blocker therapy as soon as their condition is stable.
Bisoprolol, carvedilol or nebivolol should be the first choice of beta blocker for the treatment of patients with heart failure with reduced ejection fraction.
If beta blockers are contraindicated consider using ivabradine
Pharmacological Treatment of Heart Failure Cont….
Angiotensin-Converting Enzyme Inhibitors
Patients with heart failure with reduced ejection fraction of all NYHA functional classes, should be given angiotensin-converting enzyme inhibitors.
Important adverse effects are cough, hypotension, renal impairment and hyperkalaemia.
A key but rare adverse effect, which can be life threatening (due to laryngeal involvement), is angioedema.
Any patient who experiences angioedema should have the ACE inhibitor withdrawn immediately and be prescribed an alternative agent.
Pharmacological Treatment of Heart Failure Cont.
….
Angiotensin Receptor Blockers
Angiotensin II type 1 receptor blockers (ARBs) block the biological effect of angiotensin II.
Unlike ACE inhibitors they do not produce cough as a side effect and should be used in patients who cannot tolerate an ACE inhibitor due to cough.
Patients with heart failure with reduced ejection fraction, NYHA class II-IV, who are intolerant of angiotensin-converting enzyme inhibitors should be given an angiotensin receptor blocker.
An angiotensin receptor blocker in addition to an angiotensin-converting enzyme inhibitor should be considered in patients with heart failure with reduced ejection fraction NYHA class II-IV, who are unable to tolerate a mineralocorticoid receptor antagonist.
Pharmacological Treatment of Heart Failure Cont.….
Mineralocorticoid Receptor Antagonists
Patients with heart failure with reduced ejection fraction who have ongoing symptoms of heart failure, NYHA class II-IV, LVEF ≤35%, despite optimal treatment, should be given mineralocorticoid receptor anatgonists unless contraindicated by the presence of renal impairment (chronic kidney disease stage ≥4–5) and/or elevated serum potassium concentration (K+ >5.0 mmol/l).
Eplerenone can be substituted for spironolactone in patients who develop gynaecomastia.
Pharmacological Treatment of Heart Failure Cont.….
Angiotensin Receptor/Neprilysin Inhibitors
Patients with heart failure with reduced ejection fraction who have ongoing symptoms of heart failure, NYHA class II-III, LVEF ≤40% despite optimal treatment should be given sacubitril/valsartan instead of their ACE inhibitor or ARB, unless contraindicated.
It may be considered in patients with NYHA class IV symptoms.
If the patient is already on an ACE inhibitor, the ACE inhibitor should be stopped for 36 hours before initiating sacubitril/valsartan to minimise the risk of angioedema.
Patients should be seen by a heart failure specialist with access to a multidisciplinary heart failure team before starting treatment with sacubitril/valsartan
Pharmacological Treatment of Heart Failure Cont.….
Diuretics/ Loop Diuretics
In the majority of patients with heart failure fluid retention occurs, causing ankle oedema, pulmonary oedema or both, contributing to the symptom of dyspnoea.
Diuretic treatment relieves oedema and dyspnoea.
Patients with heart failure and clinical signs or symptoms of fluid overload or congestion should be considered for diuretic therapy.
The tendency of loop diuretics to cause hypokalaemia is offset by ACE inhibitors, ARBs and spironolactone.
Pharmacological Treatment of Heart Failure Cont.….
Diuretics/ Loop Diuretics …
Care should be taken to select the dose of the loop diuretic on an individual basis, so that the dose chosen or reached should eliminate ankle or pulmonary oedema without dehydrating the patient and placing them at risk of renal dysfunction or hypotension.
The dose of diuretic should be individualised to reduce fluid retention without overtreating which may cause dehydration or renal dysfunction.
Pharmacological Treatment of Heart Failure Cont.….
Digoxin
Digoxin is usually only reserved for patients with severe HF who have not responded to other treatment
In patients with HF and sinus rhythm, digoxin may reduce symptoms and hospital admission
Digoxin should be considered as an add-on therapy for patients with heart failure in sinus rhythm who are still symptomatic after optimum therapy.
If excessive bradycardia occurs with concurrent beta blockade and digoxin therapy, digoxin should be stopped.
Pharmacological Treatment of Heart Failure Cont.….
Hydralazine and Isosorbide Dinitrate
The combination of hydralazine and isosorbide dinitrate (H-ISDN) was shown to reduce mortality in patients with HF before ACE inhibitors were introduced
Patients who are intolerant of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker due to renal dysfunction or hyperkalaemia should be considered for treatment with a combination of hydralazine and isosorbide dinitrate.
Patients with heart failure with reduced ejection fraction, NYHA class III or IV, should be given hydralazine and isosorbide dinitrate in addition to standard therapy
Monitoring of Heart failure Therapy
Monitoring parameters for patients with Heart Failure focuses on three general areas:
evaluation of functional capacity,
evaluation of volume status, and
Laboratory evaluation.
Assessment of volume status is a vital component of the ongoing care of patients with heart failure.
This evaluation provides the clinician important information about the adequacy of diuretic therapy.
Monitoring of Heart failure Therapy Cont…
Because the cardinal signs and symptoms of heart failure are caused by excess fluid retention, the efficacy of diuretic treatment is readily evaluated by the disappearance of these signs and symptoms.
The physical examination is the primary method for the evaluation of fluid retention, and specific attention should be focused on;
the patient’s body weight,
extent of jugular vein distention (JVD),
presence and severity of pulmonary congestion and,
Peripheral edema.
Monitoring of Heart failure Therapy Cont…
Specifically, in a patient with pulmonary congestion, monitoring is indicated for resolution of; rales and pulmonary edema and improvement or resolution of dyspnea on exertion, orthopnea, and Paroxysmal Nocturnal Dyspnea (PND).
Other therapeutic outcomes include an improvement in exercise tolerance and fatigue and a decrease in nocturia and heart rate.
It should be noted that, particularly with
β
-blocker therapy, symptoms may worsen initially and that it may take weeks to months of treatment before patients notice improvement in symptoms.
Routine monitoring of serum electrolytes and renal function is required in patients with heart failure.
Monitoring of Heart failure Therapy Cont…
Assessment of serum potassium is especially important because hypokalemia is a common adverse effect of diuretic therapy and is associated with an increased risk of arrhythmias and digoxin toxicity.
Serum potassium monitoring is also required because of the risk of hyperkalemia associated with ACE inhibitors, ARBs, and aldosterone antagonists.
Assessment of renal function (BUN and serum creatinine) is also an important end point for monitoring diuretic and ACE inhibitor therapy
Key Points
Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue)
Other signs of Heat Failure include elevated jugular venous pressure, pulmonary crackles and peripheral oedema which are caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress
Treatment of Heart Failure of depends on the stage of the Disease
Monitoring parameters for patients with Heart Failure focuses on three general areas which are evaluation of functional capacity, evaluation of volume status, and Laboratory evaluation
Evaluation
What is Heart Failure?
What is the pathophysiology of
Heart Failure?
What are the signs and symptoms of Heart Failure?
How is the treatment of Heart Failure
References
Wells BG, DiPiro J, Schwinghammer T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 26: Pharmacotherapy of Schizophrenia
Learning Objectives
By the end of this session students are expected to be able to:
Define schizophrenia
Explain pathophysiology of schizophrenia
Explain the clinical presentation of schizophrenia
Outline diagnosis of schizophrenia
Describe pharmacological treatment of schizophrenia
Describe the monitoring of schizophrenia therapy
Activity: Buzzing
What is Schizophrenia
?
Definition of Schizophrenia
Schizophrenia
Schizophrenia is a chronic and severe mental disorder characterised by
disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, and impaired psychosocial functioning
Pathophysiology of Schizophrenia
The pathophysiology of schizophrenia is complex.
A number of theories attempt to explain the link between altered brain function and schizophrenia, including;
T
he
Dopamine
hypothesis
The
Glutamate
hypothesis
Neurodevelopmental model
Pathophysiology of
Schizophrenia Cont…
The Dopamine Hypothesis
The first formulations of the dopamine hypothesis of schizophrenia came from post-mortem studies finding increased striatal availability of D
2
/D
3
receptors in the striatum, as well as studies finding elevated CSF levels of dopamine metabolites.
Psychotic symptoms are related to dopaminergic hyperactivity in the brain. Hyperactivity of dopaminergic systems during schizophrenia is result of increased sensitivity and density of dopamine D2 receptors in the different parts of the brain.
Pathophysiology of Schizophrenia Cont…
The glutamate hypothesis
In humans, NMDA receptor antagonists such as phencyclidine, ketamine and
dizocilpine
can produce both positive and negative psychotic symptoms-in contrast to amphetamine which produces only positive symptoms.
It has therefore been postulated that schizophrenia may result from disruption of glutamatergic neurotransmission, evident as a reduction in the function of NMDA receptors
Pathophysiology of Schizophrenia Cont
…..
Neurodevelopmental model
Neurodevelopmental
model supposes in schizophrenia the presence of “silent lesion” in the brain, mostly in the parts, important for the development of integration (frontal, parietal and temporal), which is caused by different factors (genetic, inborn, infection, trauma) during very early development of the brain in prenatal or early postnatal period of life.
It does not interfere too much with the basic brain functioning in early years, but expresses itself in the time, when the subject is stressed by demands of growing needs for integration, during formative years in adolescence and young
adulthood
Clinical presentation of schizophrenia
The symptoms of schizophrenia fall into three categories:
P
ositive
,
Negative,
Cognitive.
Clinical presentation of
schizophrenia Cont.…
Positive symptoms:
“
Positive” symptoms are psychotic behaviors not generally seen in healthy people.
People with positive symptoms may “lose touch” with some aspects of reality.
Symptoms include:
Hallucinations
Delusions
Thought disorders (unusual or dysfunctional ways of thinking)
Movement
disorders (agitated body movements)
Clinical
presentation of schizophrenia Cont.…
Negative symptoms:
“
Negative” symptoms are associated with disruptions to normal emotions and behaviors.
Symptoms include:
“Flat affect” (reduced expression of emotions via facial expression or voice tone)
Reduced feelings of pleasure in everyday life
Difficulty beginning and sustaining activities
Reduced
speaking
Clinical presentation of schizophrenia Cont.…
Cognitive symptoms:
For
some patients, the cognitive symptoms of schizophrenia are subtle, but for others, they are more severe and patients may notice changes in their memory or other aspects of thinking.
Symptoms include:
Poor “executive functioning” (the ability to understand information and use it to make decisions)
Trouble focusing or paying attention
Problems with “working memory” (the ability to use information immediately after learning it)
Diagnosis of Schizophrenia
The Diagnostic and Statistical Manual of the American Psychiatric Association, text revision (DSM-IV-TR), is the guide for diagnosing and classifying schizophrenia and other psychiatric disorders
Diagnosis of
Schizophrenia Cont…
Many patients demonstrate both positive and negative symptoms.
Patients with negative symptoms frequently have more antecedent cognitive dysfunction, poor premorbid adjustment, low level of educational achievement, and a poorer overall prognosis.
Differential diagnosis has to be made in order to exclude other psychiatric conditions that resembles schizophrenia as indicated in the table below
;
Differential Diagnosis Of Schizophrenia
Activity
: Small Group Discussion
What
is the treatment of
Schizophrenia
?
Pharmacological Treatment Of Schizophrenia
The treatment falls under Acute Phase and
Maintenance Phase
Acute Phase
AND
OR
needed.
OR
needed
Pharmacological Treatment Of
Schizophrenia Cont….
If haloperidol is unavailable give;
If patient is known to suffer from schizophrenia and is not neuroleptic naïve give:
If patient develops acute dystonia give:
OR
Anticholinergic agent, e.g
.
Biperiden
.
Pharmacological
Treatment Of Schizophrenia Cont….
For maintenance:
Haloperidol
OR
OR
Olanzepine 5–10mg (PO). Maximum dose 25mg/day
OR
Risperidone 1mg (PO) 12 hourly then increase by 1mg every 2–3 days to 2–3mg 12 hourly. Maximum dose 16mg/day 7
Monitoring of Schizophrenia Therapy
Monitoring parameters for patients with Schizophrenia focuses on three general areas:
Improvement of four positive symptoms which are suspiciousness, hallucinations, unusual thought contents and conceptual disorganization
Improvement of negative symptoms such as prolonged time to respond, emotion including unchanging facial expression, blank, expressionless face, reduced social drive, poor grooming and hygiene
Cognition
Monitoring of Schizophrenia
Therapy Cont..
Pharmacotherapeutic plan should include specific monitoring parameters for side effects.
Given the risk of weight gain, diabetes, and lipid abnormalities associated with many of the
Antipsychotics, baseline
parameters should be taken before beginning antipsychotics:
F
amily
history,
W
eight
,
H
eight
,
B
ody
mass index
,
Monitoring of Schizophrenia Therapy Cont..
Waist circumference,
Blood pressure,
Fasting plasma glucose, and
Fasting lipid profile.
Then follow-up monitoring of these parameters should be done after beginning or changing antipsychotics
.
Key Points
Schizophrenia
is a chronic and severe mental disorder characterised by
disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, and impaired psychosocial functioning
The symptoms of schizophrenia fall into three categories which are positive, negative, and cognitive
The treatment of Schizophrenia falls under Acute Phase and
Maintainance
Phase of the disease using typical or atypical antipsychotics.
Evaluation
What
is Schizophrenia?
What is the pathophysiology of
Schizophrenia?
What are the signs and symptoms of Schizophrenia?
How is the treatment of Schizophrenia?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 27: Pharmacotherapy of Epilepsy
Learning Tasks
By
the end of this session students are expected to be able to:
Define epilepsy
Explain pathophysiology of epilepsy
Explain the clinical presentation of epilepsy
Outline diagnosis of epilepsy
Describe pharmacological treatment of epilepsy
Describe the monitoring of epilepsy therapy
Activity: Buzzing
What is
Epilepsy ?
Definition of Epilepsy
The term 'epilepsy' is used to define a group of neurological disorders all of which exhibit periodic seizures.
Seizures are associated with episodic high-frequency discharge of impulses by a group
of neurons (sometimes referred to as the
focus
) in the brain.
Epilepsy implies a periodic recurrence of seizures with or without convulsions.
A seizure results from an excessive discharge of cortical neurons and is characterized by changes in electrical activity as measured by the electroencephalogram (EEG).
Definition of Epilepsy
Cont.….
A convulsion implies violent, involuntary contraction(s) of the voluntary muscles
The site of the primary discharge and the extent of its spread determine the symptoms that are produced, which range from a brief lapse of attention to a full convulsive fit lasting for several minutes, as well as odd sensations or behaviours
Table
27.1 Classification of Epilepsy
Pathophysiology of Epilepsy
Seizures result from excessive excitation, or in the case of absence seizures, from disordered inhibition of a large population of cortical neurons.
Initially, a small number of neurons fire abnormally.
Normal membrane
conductance
and inhibitory synaptic currents break down, and excess excitability spreads, either locally to produce a focal seizure or more widely to produce a generalized seizure.
This onset propagates by physiologic pathways to involve adjacent or remote areas.
The clinical manifestations depend on the site of the focus, the degree of irritability of the surrounding area of the brain, and the intensity of the impulse.
Pathophysiology of
Epilepsy Cont…
There
are multiple mechanisms that might contribute to synchronous
hyper excitability,
including:
A
lterations
in the distribution, number, type, and biophysical properties of ion channels in the neuronal membranes;
B
iochemical
modifications of receptors;
M
odulation
of second messaging systems and gene expression;
C
hanges in extracellular ion concentrations;
A
lterations in neurotransmitter uptake and metabolism in glial cells
Pathophysiology of Epilepsy Cont…
Modifications in the ratio and function of inhibitory circuits.
Local neurotransmitter imbalances between the main neurotransmitters, glutamate (excitatory) and γ -aminobutyric-acid (GABA) (inhibitory), and neuromodulators (e.g., acetylcholine, norepinephrine, and serotonin) might play a role in precipitating seizures in susceptible patients.
Clinical Presentation and Diagnosis of Epilepsy
General
In most cases, the healthcare provider will not be in a position to witness a seizure.
Many patients (particularly those with complex partial (CP) or generalized tonic
clonic
(GTC) seizures are amnestic to the actual seizure event.
Obtaining an adequate history and description of the actual event (including time course) from a witness is critically important.
Clinical Presentation and Diagnosis of Epilepsy
Cont….
Symptoms
Symptoms
of a specific seizure will depend on seizure type.
Although seizures can vary between patients, they tend to be stereotyped within an individual.
Cerebral palsy (CP) seizures
can include somatosensory or focal motor
features(jerking, loss of muscle tone or repeated movement).
CP seizures are associated with altered consciousness
.
Clinical Presentation and Diagnosis of Epilepsy Cont….
Symptoms…
Absence
seizures can be almost non-detectable with only very brief (seconds) periods of altered consciousness.
GTC (Grand mal seizures )are major convulsive episodes and are always associated with a loss of consciousness.
Cerebral palsy is a congenital disorder of movement, muscle tone or posture, it is due to abnormal brain development often before birth
Clinical Presentation and Diagnosis of Epilepsy Cont….
Signs
Interictally
(between seizure episodes), there are typically no objective or pathognomonic signs
.
Laboratory Tests
There are currently no diagnostic laboratory tests for epilepsy.
Laboratory tests can be done to rule out treatable causes of seizures (e.g., hypoglycemia, altered electrolyte concentrations, infections, etc.) that do not represent epilepsy
.
Clinical Presentation and Diagnosis of Epilepsy Cont….
Other
Diagnostic Tests
EEG(electroencephalogram) is very useful in the diagnosis of various seizure disorders.
A prolactin serum level obtained within 10 to 20 minutes of a tonic-
clonic
seizure can be useful in differentiating seizure activity from pseudo-seizure ( are seizures that occurs as a result of psychological cause such as severe mental stress) activity but not from syncope(loss of consciousness)
Magnetic resonance imaging (MRI) is very useful especially imaging of the temporal lobes
Activity
: Small Group Discussion
What
is the treatment of Epilepsy?
Pharmacological Treatment Of Epilepsy
The general approach to treatment involves assessment of seizure type and frequency, identification of treatment goals, development of a care plan, and a plan for follow-up evaluation.
During the assessment phase, it is critical to establish an accurate diagnosis of the seizure type and classification in order to select the appropriate initial AEDs
.
Pharmacological Treatment Of
Epilepsy Cont….
Pharmacological Treatment Of Epilepsy Cont….
Pharmacological Treatment Of Epilepsy Cont….
Monitoring of epilepsy Therapy
Patients should be monitored long term for seizure control, comorbid conditions, social adjustment, drug interactions, compliance, and adverse effects.
Periodic screening for comorbid neuropsychiatric disorders such as depression and anxiety is also important.
Clinical monitoring involves identifying the number and type of seizures.
Patients should record the severity and the frequency of seizures in a seizure diary. ‘
There should be a decrease in the number and/or severity of seizures.
Patients and family should be questioned regularly to determine whether they are truly seizure free
.
Key Points
The
term 'epilepsy' is used to define a group of neurological disorders all of which exhibit periodic seizures.
Seizures are associated with episodic high-frequency discharge of impulses by a group
of neurons (sometimes referred to as the
focus
) in the brain.
Seizures result from excessive excitation, or in the case of absence seizures, from disordered inhibition of a large population of cortical neurons
The general approach to treatment involves assessment of seizure type and frequency, identification of treatment goals, development of a care plan, and a plan for follow-up evaluation
Evaluation
What
is Epilepsy?
What is the pathophysiology of
Epilepsy?
What are the signs and symptoms of Epilepsy?
How is the treatment of Epilepsy
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 28: Pharmacotherapy of Hepatitis B
Learning Objectives
By the end of this session students are expected to be able to:
Define hepatitis B
Explain pathophysiology of hepatitis B
Explain the clinical presentation of hepatitis B
Outline diagnosis of hepatitis B
Describe pharmacological treatment of hepatitis B
Describe the monitoring of hepatitis b therapy
Activity: Buzzing
What is Hepatitis
B ?
Definition of
Hepatitis B
Hepatitis
B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV).
It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer.
HBV is transmitted sexually, parenterally, and
perinataly
.
In areas of high HBV prevalence, perinatal transmission from mother to infant is most common, whereas in areas of intermediate prevalence, horizontal transmission from child to child is most common.
Sexual contact, both homosexual and heterosexual, and injection drug use are the predominant forms of transmission in low-endemic countries
Pathophysiology of Hepatitis B
The life cycle of HBV is complex but, essentially, it acts as a stealth virus by evading the immune system.
During the first stage of infection, the HBV
virion
(virus particle) attaches to a liver cell (hepatocyte) then penetrates the hepatocyte’s cytoplasm
The HBV
virion
is uncoated, which means that
nucleocapsids
can move into the hepatocyte’s nucleus and convert the DNA to covalently closed circular DNA (
cccDNA
) – a double-stranded DNA structure
The
cccDNA
is very stable and can stay in the host nucleus for many months in chronic disease
Pathophysiology of Hepatitis
B Cont…
The virus makes copies of itself in a process that lacks “proof reading ability”, which allows the virus to mutate
The newly formed HBV
virions
are released into the bloodstream, from where they invade other hepatocytes and repeat the replication process.
It is thought that HBV causes inflammation and progressive fibrosis in the infected liver by triggering the immune system to attack the hepatocytes
Clinical Presentation And Diagnosis Of Hepatitis B
The majority of acute HBV infections are also asymptomatic but around 30% of adults will present with the following symptoms;
Signs and symptoms
Easy fatigability, anxiety, anorexia, and malaise
Ascites, jaundice, variceal bleeding, and hepatic encephalopathy can manifest with liver
decompensation(loss of brain function when a damaged liver doesn't remove toxins from blood
)
Clinical Presentation And Diagnosis Of Hepatitis
B Cont…
Signs and
symptoms….
Hepatic
encephalopathy is associated with hyper excitability, impaired mentation, confusion,
obtundation
(loss of consciousness), and eventually coma(a period of prolonged unconsciousness)
Vomiting and seizures
Clinical Presentation And Diagnosis Of Hepatitis B Cont…
Laboratory tests
Presence of hepatitis B surface antigen >6
mo
Intermittent elevations of hepatic transaminase (alanine transaminase
Liver biopsies for pathologic classification as chronic persistent hepatitis, chronic active hepatitis, or cirrhosis
Activity
: Brainstorming
What
is the treatment of Hepatitis B infection??
Pharmacological Treatment Of Hepatitis B
HBV infections are not curable; rather, the goals of therapy are to increase the chances for
seroclearance
, prevent disease progression to cirrhosis and HCC, and to minimize further injury in patients with ongoing liver damage
.
Pharmacological treatment includes
;
Tenofovir
(PO) 300mg once daily for life
OR
Entecavir
(PO) 0.5mg–1mg once daily for life
OR
Lamuvidine
(PO) 100mg once daily for life
Pharmacological Treatment Of Hepatitis
B Cont….
Prophylaxis against HBV can be achieved by vaccination or by passive immunity in
postexposure
cases with hepatitis B immunoglobulin.
Vaccination is the most effective strategy to prevent infection
Monitoring Of Hepatitis B Therapy
Response to therapy is monitored by;
Biochemical (normalization of ALT levels),
Histologic examination of liver cells from biopsy (a minimum 2-point decrease in histology activity compared with baseline biopsy), and
Virologic
response (undetectable serum HBV DNA levels and loss of HBeAg in HBeAg-positive patients).
Maintenance of viral suppression is defined as durability of response.
In HBeAg-positive patients, successful therapy includes loss of HBeAg status and seroconversion to anti-HBeAg.
Key Points
Hepatitis
B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV).
It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer
HBV infections are not curable; rather, the goals of therapy are to increase the chances for
seroclearance
, prevent disease progression to cirrhosis and HCC, and to minimize further
Evaluation
What
is Hepatitis B?
What is the pathophysiology of
Hepatitis B?
What are the signs and symptoms of Hepatitis B?
How is the treatment of
Hepatitis B?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 29: Pharmacotherapy of Cholera
Learning Objectives
By the end of this session students are expected to be able to:
Define cholera
Explain pathophysiology of cholera
Explain the clinical presentation of cholera
Outline diagnosis of cholera
Describe pharmacological treatment of cholera
Describe the monitoring of cholera therapy
Activity: Buzzing
What is Cholera?
Definition
of Cholera
Cholera
is an acute gastrointestinal infection caused by
Vibrio
cholerae
.
Infection occurs through ingestion of contaminated water or food by human faeces leading to severe diarrhoea and emesis associated with body fluid and electrolyte depletion
.
Pathophysiology of Cholera
V.
cholerae
is a gram-negative bacillus sharing similar characteristics with the family
Enterobacteriaceae
.
Most pathology of cholera results from an enterotoxin (cholera toxin) produced by the bacteria.
Conditions that reduce gastric acidity, such as the use of antacids, histamine receptor blockers, or proton pump inhibitors, or infections with
Helicobacter pylori,
increase
the
risk
for clinical disease.
Cholera toxin stimulates adenylate
cyclase,which
increases intracellular cyclic adenosine monophosphate (
cAMP
) and results in inhibition of sodium and chloride
absorption
by
microvilli and promotes the secretion of chloride and water by crypt cells.
Pathophysiology of
Cholera Cont…
The toxin likely acts along the entire intestinal tract, but most fluid loss occur in the duodenum.
The net effect of the cholera toxin is isotonic fluid secretion (primarily in the small intestine) that exceeds the absorptive capacity of the intestinal tract (primarily the colon).
This results in the production of watery diarrhea with electrolyte concentrations similar to that of plasma
Clinical presentation and diagnosis of Cholera
A sudden onset of painless watery diarrhoea that may quickly become severe with profuse watery stools, vomiting, severe dehydration and muscular cramps, leading to hypovolemic shock and death
The stool has a characteristic “rice water” appearance (non-bilious, grey, slightly cloudy fluid with flecks of mucus, no blood and inoffensive odour)
Laboratory evidence of dark field microscopic isolation of motile curved bacillus on a wet mount of fresh stool specimen OR
Isolation of bacteria through stool culture on TCBS agar.
Activity
: Brainstorming
What is the treatment of cholera
?
Pharmacological Treatment of Cholera
Treat according to Plan as indicated in the Standard Treatment Guideline (Tanzania)
Plan A: No dehydration,
Plan B: Moderate dehydration and
Plan C: Severe dehydration.
When a case of cholera is suspected at home, advise to rehydrate the patient using ORS if available while preparing to take a patient to the nearest health facility or Cholera Treatment Centre
Pharmacological Treatment of
Cholera Cont..
Manage a suspected cholera case in an isolation ward or in an established Cholera Treatment Centre
Assess the patient's level of dehydration as per National Guidelines for Prevention and Control of Cholera. It is of paramount importance to make correct diagnosis and administer the right treatment according to the Treatment
Pharmacological Treatment of Cholera Cont..
For severe Rehydration
Administer intravenous (IV) fluid immediately to replace fluid deficit; Use Ringer Lactate solution or, if that is not available, 0.9% sodium chloride solution. Give 100 ml/kg IV in 3 hours, 30 ml/kg as rapidly as possible (within 30 min) then 70 ml/kg in the next 2.5 hours
After the initial 30 ml/kg has been administered, the radial pulse should be strong and blood pressure should be normal. If the pulse is not yet strong, continue to give IV fluid rapidly. Administer ORS solution (about 5 ml/kg/hour) as soon as the patient can drink, in addition to IV fluid
If the patient can drink, begin giving A: oral rehydration salt solution (ORS) by mouth while the drip is being set up; ORS can provide the potassium, bicarbonate, and glucose that saline solution lacks.
Pharmacological Treatment of Cholera Cont..
Give an oral antibiotic to patients with severe dehydration as follows:
Adults
(Not for pregnant women) :
Folic acid (PO) 5mg once daily for the duration of the treatment.
Expectant mothers: Erythromycin (PO) 500mg 8 hourly for 5 days
A: Co-
trimoxazole
Pharmacological Treatment of Cholera Cont..
Folic acid AND Zinc.
Folic acid AND
Zinc
Start feeding 3-4 hours after oral rehydration begins. Preferably, give antibiotics with food to minimize vomiting
Give
ORS for rehydration; they have to be taken frequently
Pharmacological Treatment of Cholera Cont..
For moderate Dehydration
Reassess after four hours; if improved, continue giving WHO based ORS, in quantity corresponding to losses (
eg
If not improved, treat as severe If no signs of dehydration
Pharmacological Treatment of Cholera Cont..
For moderate Dehydration
….
Patients
who have no signs of dehydration when first observed can be treated at home
Give these patients ORS packets to take home, enough for 2 days
Demonstrate how to prepare and give the solution
Instruct the patient or the caretaker to return if any of the following signs develop; increased number of watery stools repeated vomiting or any signs indicating other problems (
eg
, fever, blood in stool)
Monitoring of Cholera therapy
It is important to monitor for resolution of the
symptoms,
adherence to medicines and adverse drug reactions and severe side effects; in case of any they should be reported and addressed
accordingly
Key
Points
Cholera
is an
infection of
the small
intestine by
some strains of the bacterium Vibrio
cholerae
.
Symptoms may range from none, to mild, to severe and the classic symptom is large amounts of watery
diarrhea
that lasts a few days.
Diarrhea
can be so severe that it leads within hours to severe dehydration and electrolyte imbalance
It is spread mostly by unsafe water and unsafe food that has been contaminated with human
feces
containing
the bacteria
Cholera can be successfully treated with oral rehydration therapy (ORT) and chemotherapy
Evaluation
What
is Cholera?
What is the pathophysiology of
Cholera?
What are the signs and symptoms of Cholera?
How is the treatment of Cholera?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 30: Pharmacotherapy of Shigellosis
Learning objectives
By the end of this session students are expected to be able to:
Define shigellosis
Explain pathophysiology of shigellosis
Explain the clinical presentation of shigellosis
Outline diagnosis of shigellosis
Describe pharmacological treatment of shigellosis
Describe the monitoring of shigellosis therapy
Activity: Buzzing
What is Shigellosis?
Definition of Shigellosis
Shigellosis
Shigellosis is spread by means of fecal-oral, by ingestion of contaminated food and water and it leads to bacillary dysentery.
Pathophysiology of shigellosis
The source of infection is the feces of infected people or convalescent carriers; humans are the only natural reservoir for
Shigella
.
Direct spread is by the fecal-oral route. Indirect spread is by contaminated food and fomites.
Flies serve as vectors.
Because
Shigella
is relatively resistant to gastric acid, ingestion of as few as 10 to 100 organisms can cause disease.
Pathophysiology of shigellosis Cont….
Shigella
organisms penetrate the mucosa of the colon, causing mucus secretion, hyperemia, leukocytic infiltration, edema, and often superficial mucosal ulcerations.
Shigella dysenteriae
type 1 (commonly present in travelers returning from endemic areas) produces Shiga toxin, which causes marked watery diarrhea and sometimes hemolytic-uremic syndrome(HUS)
Clinical Presentation and Diagnosis of Shigellosis
Signs and Symptoms
Acute abdominal cramping, high-grade fever, emesis and large-volume watery diarrhea,
Tenesmus, urgency, fecal incontinence, mucoid bloody diarrhea,
Severe headache, lethargy, meningismus, delirium and convulsions,
Hemolytic uremic syndrome (HUS),
microangiopathic hemolytic anemia, thrombocytopenia, and renal failure,
Profound dehydration and hypoglycemia
Clinical Presentation and Diagnosis of Shigellosis Cont…
Diagnosis
Laboratory evidence of microscopic isolation of the bacteria from stool or rectal swabs specimens OR
Stool culture for suspected cases in early course of infection OR
An enzyme immunoassay (ELISA) for shiga toxin detection in stool for S. dysenteriae type-1.
Activity: Small Group Discussion
What is the treatment of Shigellosis?
Pharmacological treatment of Shigellosis
Treatment
Ciprofloxacin (PO) 500mg 12 hourly for 5 days OR
Nalidixic acid (PO) 1000mg 6 hourly for 7 days OR
Erythromycin (PO) 250mg 6 hourly for 5 days
Monitoring of Shigellosis Therapy
It is important to monitor for resolution of the symtoms, adherence to medicines and adverse drug reactions and severe side effects; in case of any they should be reported and addressed accordingly
Key Points
Shigella infection (shigellosis) is an intestinal disease caused by a family of bacteria known as shigella.
The main sign of shigella infection is diarrhea, which often is bloody.
Shigella can be passed through direct contact with the bacteria in the stool.
Shigella infection usually clears up without complications, although chemotherapy may be needed to some patients
It may take weeks or months before the bowel habits return to normal
.
Evaluation
What is Shigellosis?
What is the pathophysiology of
Shigellosis?
What are the sACigns and symptoms of Shigellosis?
How is the treatment of Shigellosis?
References
Wells BG, DiPiro J, Schwinghammer T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed): New York, NY: McGraw-Hill.
END
PST 06106
Basic Pharmacotherapy
Session 31: Pharmacotherapy of Breast
Cancer
Learning Objectives
By the end of this session students are expected to be able to:
Define breast cancer
Explain pathophysiology of breast cancer
Explain the clinical presentation of breast cancer
Outline diagnosis of breast cancer
Describe pharmacological treatment of breast cancer
Describe the monitoring of breast cancer
therapy
Definition of Breast Cancer
Breast cancer is a malignancy originating from breast tissue.
Disease confined to a localized breast lesion is referred to as early, primary, localized, or curable
Disease detected clinically or radiologically in sites distant from the breast is referred to as advanced or metastatic breast cancer (MBC), which is usually incurable.
Breast cancer cells often spread undetected by
contiguity(bordering/being in contact with something),
lymph channels, and through the blood early in the course of the disease, resulting in metastatic disease after local therapy.
The most common metastatic sites are lymph nodes, skin, bone, liver, lungs, and brain
.
Activity: Buzzing
What is the pathophysiology of breast cancer?
Pathophysiology of Breast Cancer
Breast cancer is a malignant tumor that starts in the cells of the
breast
,
Like
other cancers, there are several factors that can raise the risk of getting breast cancer:
Female gender
Age
Previous breast cancer
Benign breast disease
Hereditary factors (family history of breast cancer)
Pathophysiology of Breast
Cancer
Cont
…
Early age at menarche
Late age at menopause
Late age at first full-term pregnancy
Obesity (postmenopausal)
Low physical activity
High-dose exposure to ionizing radiation early in life
Pathophysiology of Breast Cancer
Cont.…
Damage to the DNA and genetic mutations can lead to breast cancer; have been experimentally linked to estrogen exposure.
Some
individuals inherit defects in the DNA and genes like the BRCA1, BRCA2 and P53 among others.
Those
with a family history of ovarian or breast cancer thus are at an increased risk of breast cancer
.
BRCA1
and
BRCA2
are human genes that produce tumor suppressor proteins.
These
proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of each cell’s genetic material.
When
either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly
..
Pathophysiology of Breast Cancer
Cont
…
The immune system normally seeks out cancer cells and cells with damaged DNA and destroys them.
Breast
cancer may be a result of failure of such an effective immune defense and surveillance.
These are several signalling systems of growth factors and other mediators that interact between stromal cells and epithelial cells. Disrupting these may lead to breast cancer as well.
Clinical Presentation and Diagnosis of Breast Cancer
The patient may not have any symptoms, as breast cancer may be detected in asymptomatic patients though routine screening mammography.
The initial sign in more than 90% of women with breast cancer is a painless lump that is typically solitary, unilateral, solid, hard, irregular, and
non mobile
.
Less common initial signs are pain and nipple changes.
More advanced cases present with prominent skin
oedema,
redness, warmth, and induration.
Symptoms of MBC depend on the site of metastases, but may include bone pain, difficulty breathing, abdominal pain or enlargement, jaundice, and mental status changes.
Many women first detect some breast abnormalities themselves, but it is increasingly common for breast cancer to be detected during routine screening mammography in asymptomatic women
.
Clinical Presentation and Diagnosis of Breast
Cancer Cont.….
Staging
Stage
is based on the size of the primary tumor, presence and extent of lymph node involvement, and presence or absence of distant metastases. Simplistically stated, these stages may be represented as
follows:
Early Breast Cancer
Stage 0: Carcinoma in situ or disease that has not invaded the basement
membrane.(is
a group of abnormal cells that are found only in the place where they first formed in the body
)
Stage I: Small primary
tumour
without lymph node involvement.
Stage II: Involvement of regional lymph nodes.
Clinical Presentation and Diagnosis of Breast Cancer Cont.….
Locally Advanced Breast Cancer
Stage III: Usually a large tumor with extensive nodal involvement in which node or tumor is fixed to the chest wall; also includes inflammatory breast cancer, which is rapidly progressive.
Advanced or Metastatic Breast Cancer
Stage IV: Metastases in organs distant from the primary
tumour.
Clinical Presentation and Diagnosis of Breast Cancer Cont.….
Clinical Presentation
Local
Signs and Symptoms
A painless, palpable lump is most common.
Less common: pain; nipple discharge, retraction or dimpling;
Skin edema, redness or warmth.
Palpable local–regional lymph nodes may also be
present
Signs and Symptoms of Systemic Metastases
Depends on the site of metastases, but may include bone pain, difficulty breathing, abdominal pain or enlargement, jaundice, mental status
changes
Clinical Presentation and Diagnosis of Breast Cancer Cont.….
Diagnosis
Initial workup for a woman presenting with a localized lesion or suggestive symptoms should include a careful history, physical examination of the breast, three-dimensional mammography, and, possibly, other breast imaging techniques such as ultrasound.
Breast biopsy is indicated for a mammographic abnormality that suggests malignancy or a mass that is palpable on physical examination.
Clinical Presentation and Diagnosis of Breast Cancer Cont.….
Laboratory Tests
Tumor markers such as cancer antigen (CA) or carcinoembryonic antigen (CEA) may be elevated.
Alkaline phosphatase or liver function tests may be elevated in metastatic disease.
Clinical Presentation and Diagnosis of Breast Cancer Cont.….
Other Diagnostic Tests
Mammogram
(with or without ultrasound, breast MRI, or both)
Biopsy for pathology review and determination of tumor estrogen/progesterone receptor (ER/PR) status and
HER2
status.
Systemic staging tests may include: chest x-ray, chest CT, bone scan, abdominal CT or ultrasound, or MRI
.
Activity
: Small Group Discussion
What
is the pharmacological treatment of breast cancer?
Pharmacological Treatment of Breast Cancer
Chemotherapy is indicated for almost all patients as neo-adjuvant, adjuvant or palliative. Patients, who are planned for surgery and have ≥ T3 tumors, should receive neo-adjuvant chemotherapy before
operation
Several
regimens are available. Few of them include
:
Dosing schedules for combinations for HER 2 negative disease:
Pharmacological Treatment of Breast
Cancer
Cont
…
Describes cancer cells that do not have a large amount of a protein called HER2 on their surface. In normal cells, HER2 helps to control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface
Pharmacological Treatment of Breast Cancer
Cont
…
weeks.
Doxorubicin
60 mg/m2 IV on day1 + Cyclophosphamide 600 mg/m2 IV day 1 given every 21 days for 4 cycles then followed by Paclitaxel 175 mg/m2 by 3 h IV infusion day 1, given every 21 days for 4 cycles OR Docetaxel 100 mg/m2 IV day 1 Cycled every 21 days for 4 cycles.
NOTE:
FBC(Full blood count), RFT(Renal function test), LFT( Liver function test)
before each cycle
Pharmacological Treatment of Breast Cancer
Cont
…
Dosing schedule for combinations for HER2-Positive disease:
wks
AND
Pharmacological Treatment of Breast Cancer
Cont
…
Endocrine
therapy
Monitoring
of Breast Cancer Therapy
Monitoring response to treatment is a key element in the management of breast cancer that involves several different viewpoints from surgery, radiology, and medical oncology
After completion of adjuvant therapy, follow up care focuses on detecting recurrent disease with the intention of improving long term survival
Monitor patient adherence to the treatment as maintaining dose intensity has been demonstrated to be important in the cure of disease
Tumor response to a particular treatment regimen may be measured by clinical chemistry such as liver enzyme elevation in a patient with hepatic metastases or tumor markers, or imaging techniques such as bone scans or chest radiographs.
Monitoring
of Breast Cancer
Therapy
Cont
…
However, assessment of the patient’s clinical status and symptom control is often adequate to evaluate response to the therapy administered.
In the patient with metastatic breast cancer, it is common to initiate hormonal therapy or chemotherapy and continue administration until signs and symptoms of disease progression or new signs and symptoms present
Monitor the adverse effects of drugs and manage them accordingly
Key Points
Breast
cancer is a malignancy originating from breast tissue. Disease confined to a localized breast lesion is referred to as early, primary, localized, or curable
Disease detected clinically or radiologically in sites distant from the breast is referred to as advanced or metastatic breast cancer (MBC), which is usually incurable
Key
Points Cont.….
Damage to the DNA and genetic mutations can lead to breast cancer; have been experimentally linked to estrogen exposure. Some individuals inherit defects in the DNA and genes like the BRCA1, BRCA2 and P53 among others. Those with a family history of ovarian or breast cancer thus are at an increased risk of breast cancer.
Chemotherapy is indicated for almost all patients as neo-adjuvant, adjuvant or palliative. Patients, who are planned for surgery and have ≥ T3 tumors, should receive neo-adjuvant chemotherapy before operation
Evaluation
What
is Breast Cancer?
What is the pathophysiology of Breast Cancer?
How is Breast Cancer diagnosed?
How is monitoring of Breast Cancer therapy done?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy (2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 32: Pharmacotherapy of Prostate Cancer
Learning Tasks
By the end of this session students are expected to be able to:
Define prostate cancer
Explain pathophysiology of prostate cancer
Explain the clinical presentation of prostate cancer
Outline diagnosis of prostate cancer
Describe pharmacological treatment of prostate cancer
Describe the monitoring of prostate cancer therapy
Definition of Prostate Cancer
Prostate cancer is a malignant neoplasm that arises from the prostate gland.
Prostate cancer has an indolent course; localized prostate cancer is curable by surgery
or
radiation
therapy, but advanced prostate cancer is not yet curable.
The most common type of prostate cancer is adenocarcinoma (95 %)
Tumors
are stratified by T stage, Gleason score (GS), and PSA into three prognostic groups of low, intermediate and high risk.
Definition of Prostate Cancer
Cont
…
Patient can be offered appropriate treatment options according to stage of disease, prognostic risk group and estimated survival taking into account performance status and comorbidity.
Activity: Buzzing
What is the pathophysiology of prostate cancer?
Pathophysiology of Prostate Cancer
The prostate gland is a part of the male reproductive system that helps to make and store seminal fluid.
Because of its location, prostate disease often affects urination, ejaculation, and rarely defecation.
Prostate cancer begins when normal
semen screening
prostate gland cells mutate into cancer cells.
The region of prostate gland where the adenocarcinoma is most common is the peripheral zone.
Pathophysiology of Prostate
Cancer
Cont
…
Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostate intraepithelial neoplasia(PIN).
Overtime, these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.
Eventually
, the tumor may grow large enough to invade nearby organs such as the seminal vesicles, or the rectum, or the tumor cells may develop the ability to travel in the blood stream and lymphatic system.
The invasion of other organs is called metastasis.
Prostate cancer most commonly metastasizes to the bones, lymph nodes, and may invade rectum, bladder and lower ureters after local progression.
Clinical presentation and Diagnosis of Prostate Cancer
Localized Disease
Asymptomatic
Locally Invasive Disease
Impotence
Prostatic symptoms are associated with advanced stages of the disease, which include: reduced potency, urinary frequency and nocturnal, poor stream, hesitancy and terminal
dribbling
Clinical presentation and Diagnosis of Prostate
Cancer Cont.….
Advanced Disease
Back pain
Cord compression
Lower extremity edema
Anemia
Weight loss
Very often patients may present with bone pain including backache or pathological
fracture
Diagnostic and Staging Workup for prostate Cancer
Activity
: Small Group Discussion
What are the drugs treatments for prostate cancer?
Pharmacological Treatment of Prostate Cancer
Luteinizing Hormone–Releasing Hormone Agonists
LHRH agonists are a reversible method of androgen ablation and are as effective
as orchiectomy
.
Leuprolide acetate, leuprolide depot, leuprolide implant,
triptorelin
depot,
triptorelin
implant, and
goserelin
acetate implant are currently available.
Dosing intervals range from once monthly to every 16 weeks.
Leuprolide implant is a
miniosmotic
pump that delivers daily doses for 1 year.
The most common adverse effects of LHRH agonists include disease flare-up during the first week of therapy (
eg
, increased bone pain or urinary symptoms), hot flashes, erectile impotence, decreased libido, and injection-site reactions.
Pharmacological Treatment of Prostate
Cancer
Cont
….
Luteinizing Hormone–Releasing Hormone Agonists…..
Use
of an antiandrogen (
eg
,
flutamide
,
bicalutamide
, or
nilutamide
) prior to initiation of LHRH therapy and for 2 to 4 weeks after is a strategy to minimize initial tumor flare.
Decreases in bone mineral density complicate androgen deprivation therapy (ADT), resulting in increased risk of osteoporosis, osteopenia, and skeletal fractures.
Calcium and vitamin D supplements and a baseline bone mineral density are recommended.
Pharmacological Treatment of Prostate Cancer
Cont
….
Gonadotropin-Releasing Hormone Antagonists
Degarelix binds reversibly to GnRH receptors in the pituitary gland, reducing the production of testosterone to castrate levels in 7 days or less
A major advantage of
degarelix
over LHRH agonists the lack of tumor flares.
Degarelix is administered as a subcutaneous injection every 28 days
Injection site reactions are the most frequently reported adverse effects and include pain, erythema, swelling, induration, and nodules
.
Pharmacological Treatment of Prostate Cancer
Cont
….
Antiandrogens
Monotherapy with
flutamide
,
bicalutamide
, and
nilutamide
is no longer
recommended
due
to decreased efficacy as compared with patients treated with LHRH agonist therapy
Antiandrogens are indicated for advanced prostate cancer only when
combined with an LHRH agonist (
flutamide
and
bicalutamide
]) or
orchiectomy
(
nilutamide
). In combination, antiandrogens can reduce the LHRH
agonist–
inducedflare
.
Enzalutamide is approved as a single agent in metastatic hormone-resistant
prostate
cancer
patients who have previously received docetaxel
.
Pharmacological Treatment of Prostate Cancer
Cont
….
Chemotherapy
It is mainly reserved for hormonal-refractory prostate cancer. The most common adverse events include nausea, alopecia, and myelosuppression.
Cabazitaxel
Neutropenia, febrile neutropenia, neuropathy, and diarrhea are the most significant toxicities.
For Bone metastases/osteolytic/
tumour
induced hypercalcemia:
Zolendronic
acid IV 4mg over 15min given 4 Weekly
Monitoring Of Prostate Cancer Therapy
Monitor primary tumor size, involved lymph nodes, and tumor marker response such as PSA with definitive, curative therapy
PSA level is checked every 6 months for the first 5 years, then annually.
With metastatic disease, clinical benefit can be documented by evaluating performance status, weight, quality of life, analgesic requirements, and PSA or DRE at 3-month intervals
.
Monitoring of Prostate Cancer Therapy
Monitor
primary tumor size, involved lymph nodes, and tumor marker response such as PSA with definitive, curative therapy
PSA level is checked every 6 months for the first 5 years, then annually.
With metastatic disease, clinical benefit can be documented by evaluating performance status, weight, quality of life, analgesic requirements, and PSA or DRE at 3-month intervals.
Key Points
Prostate
cancer is a malignant neoplasm that arises from the prostate gland. Prostate
cancer has an indolent course; localized prostate cancer is curable by surgery or
radiation therapy, but advanced prostate cancer is not yet curable
There are different stages of Prostate Cancer according to
Glearson
score
Metastatic spread can occur by local extension, lymphatic drainage, or
hematogenous
dissemination
Key
Points
Cont
…
The diagnosis is based on various diagnostic criteria and various diagnostic tests such as
abdominal and pelvic USS and or CT Scan, Pelvic MRI in early stage
disease , Bone
scan
etc
The
common drugs used for the treatment of Prostate Cancer are LHRH agonists and
GnRH
antagonists
Monitoring therapy should be done by checking primary tumor size, involved lymph nodes, and tumor marker response such as PSA with definitive, curative therapy. PSA level should checked every 6 months for the first 5 years, then annually.
Evaluation
What
is Prostate Cancer?
What is the pathophysiology of Prostate Cancer?
How is Prostate Cancer diagnosed?
What is the first line treatment of Prostate Cancer
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
PST 06106
Basic Pharmacotherapy
Session 33: Pharmacotherapy of Oropharyngeal Candidiasis
Learning Tasks
By
the end of this session students are expected to be able to:
Define oropharyngeal candidiasis
Explain pathophysiology of oropharyngeal candidiasis
Explain the clinical presentation of oropharyngeal candidiasis
Outline diagnosis of oropharyngeal candidiasis
Describe pharmacological treatment of oropharyngeal candidiasis
Describe the monitoring of oropharyngeal candidiasis therapy
Definition of Oropharyngeal Candidiasis
Oropharyngeal candidiasis
(OPC), or
thrush,
refers to an infection of the oral mucosa.
Candida
is responsible for the majority of
oralfungal
infections, and
C.
albicans
is the principal species causing the infection, commonly referred to as
candidiasis
The infection may extend into the esophagus, causing esophageal candidiasis.
Activity: Buzzing
What
is the pathophysiology of oropharyngeal candidiasis?
Pathophysiology of Oropharyngeal Candidiasis
The pathogenesis of OPC is most clearly elucidated in the setting of HIV infection.
There appear to be several levels of immune defense against the development of OPC in HIV-infected persons, and they involve both systemic and local immunity.
The primary line of host defense against
C.
albicans
is cell-mediated immunity (CMI) at the mucosal surfaces, which is mediated by CD4 T cells.
The efficacy of the CD4 T cells is reduced when the number of cells drops below a protective threshold, and protection against infection becomes dependent on secondary or local immune mechanisms
Pathophysiology of Oropharyngeal
Candidiasis
Cont
….
When the number of CD4 T cells drops too low, recruitment of these cells to the oral cavity is impaired.
The CD4 T-cell count has been considered as the hallmark predictor for development of OPC.
The changeover of the role of
Candida
species from commensal to pathogenic in the human host usually occurs when breakdown in these host defenses occurs.
Other virulence factors are the adhesive ability of
C.
albicans
to epithelial cells and proteins and its ability to invade host cells
by means of phospholipase and proteinase enzymes.
Pathophysiology of Oropharyngeal Candidiasis
Cont
….
This may be one
of the factors leading to OPC in non-HIV-infected individuals.
Other
components of the pathogenesis in the absence of HIV that have been
postulated are the ability of the
Candida
species to adhere to buccal
epithelial cells including those patients receiving broad-spectrum antimicrobial therapy.
Clinical Presentation and Diagnosis of Oropharyngeal Candidiasis
General
The clinical features can be quite diverse
Symptoms
Symptoms are diverse and range from none to sore, painful mouth, burning tongue, metallic taste, and dysphagia and odynophagia with involvement of the hypopharynx
Signs
Signs are variable and can include diffuse erythema and white patches on the surfaces of the buccal mucosa, throat, tongue, or gums; constitutional signs are absent
Clinical Presentation and Diagnosis of Oropharyngeal Candidiasis
Cont
….
Laboratory tests
Scraping of an active lesion for microscopic examination can help confirm the diagnosis (presence of
pseudohyphae
and budding yeast) but is usually not necessary
Cultures are not necessary because isolation of
Candida
species does not distinguish between colonization and true infection; cultures can be taken in patients responding poorly to therapy to determine the infecting species and to predict likely drug resistance
Activity
: Small Group Discussion
What are the drugs treatments for oropharyngeal candidiasis
?
Pharmacological Treatment of Prostate Cancer
The management of OPC should be individualized for each patient, taking into consideration the underlying immune status, other concurrent mucosal and medical diseases, concomitant medications, and exogenous infectious sources.
In HIV-infected patients with inadequately controlled disease, antifungal treatment produces only a transient clinical response, and the relapse rates are higher than in other patient populations.
Topical therapies should be the first choice for milder forms of infections
Therapeutic Options for Mucosal Candidiasis
Monitoring of Oropharyngeal Candidiasis Therapy
Efficacy end points for oropharyngeal and esophageal candidiasis include rapid relief of symptoms and prevention of complications without early relapse after completion of the course of therapy.
Symptomatic relief of presenting signs and symptoms generally occurs within 48 to 72 hours of starting therapy, with complete resolution by 7 to 10 days.
Patients should be advised about the time course and told to return for reassessment when signs and symptoms recur.
It is usually unnecessary for the patient to be reassessed soon after finishing the treatment course.
Monitoring of Oropharyngeal Candidiasis Therapy
Cont
…
However, HIV patients should be questioned and examined for the occurrence of
mucosal
candidiasis
as part of their regular follow-up.
The frequency of monitoring can be more often in neutropenic patients
because
of
concern for dissemination of candidiasis.
During the period of neutropenia, temperature should be monitored daily, as well
as
signs
of dissemination.
Efficacy of the antifungal agent is partly influenced by patient adherence to the medication regimen.
Patients must be counseled on proper administration and dosing, in particular for
topical
agents
Monitoring of Oropharyngeal Candidiasis Therapy
Cont
…
Safety end points include monitoring for occurrence of the relevant drug side effects and drug interactions
Hepatotoxicity can occur when azole therapy is prolonged beyond 7 to 10 days or high doses are used.
Periodic monitoring of liver enzymes (alanine transaminase and aspartate amino-transferase) should be considered, especially if prolonged therapy (longer than 21 days) is anticipated.
Key Points
Oropharyngeal
candidiasis
(OPC), or
thrush,
refers to an infection of the oral mucosa.
Symptoms are diverse and range from none to sore, painful mouth, burning tongue, metallic taste, and dysphagia and odynophagia with involvement of the hypopharynx
The management of OPC should be individualized for each patient, taking into consideration the underlying immune status, other concurrent mucosal and medical diseases, concomitant medications, and exogenous infectious sources
Evaluation
What
is Oropharyngeal Candidiasis?
What is the pathophysiology of Oropharyngeal Candidiasis?
How is Oropharyngeal Candidiasis?
What is the first line treatment of Oropharyngeal Candidiasis?
REFER
Students to Handout 33.1: Risk Factors for the Development of Oropharyngeal and/or Esophageal Candidiasis
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
: New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
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