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NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Shigellosis Basic Pharmacotherapy • Source Session/Topic 30 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 ← Previous TopicNext Topic →View all Basic Pharmacotherapy topicsOpen Complete Full Notes PDF / OFFLINE NOTES Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP WhatsApp: 255620339260

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Cholera Basic Pharmacotherapy • Source Session/Topic 29 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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) : Doxycycline (PO) 300 mg as a single dose or 5mg/kg single dose OR Ciprofloxacin (PO) 1g stat or 15mg/kg 12 hourly for 3 days AND Folic acid (PO) 5mg once daily for the duration of the treatment. Expectant mothers: Erythromycin (PO) 500mg 8 hourly for 5 days Children: A: Erythromycin syrup (PO) 12.5mg/kg 6 hourly for 3 days OR A: Co- trimoxazole 48mg/kg once a day for 3 days AND Pharmacological Treatment of Cholera Cont.. Folic acid AND Zinc. For adolescents: Ciprofloxacin (PO) 12mg/kg 2 times for 3 days OR Doxycycline (PO) 300mg as single dose or 5mg/kg single dose AND 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 Give oral rehydration, approximately 75-100ml/kg in the first four hours Reassess after four hours; if improved, continue giving WHO based ORS, in quantity corresponding to losses ( eg . after each stool) or 10 to 20ml/kg. 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,

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Hepatitis B Basic Pharmacotherapy • Source Session/Topic 28 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 and aspartate transaminase) and hepatitis B virus DNA >20,000 IU/mL (105 copies/mL) 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. ← Previous TopicNext Topic →View all Basic Pharmacotherapy topicsOpen Complete Full Notes PDF / OFFLINE NOTES Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP WhatsApp: 255620339260

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Epilepsy Basic Pharmacotherapy • Source Session/Topic 27 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Schizophrenia Basic Pharmacotherapy • Source Session/Topic 26 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 Haloperidol 5 mg (IM) repeat in 30–60 minutes, if required. (Max dose: 20 mg within 24 hours) AND Diazepam 10 mg (IV), stat. Repeat after 30–60 minutes if needed. OR Promethazine 25–50 mg (deep IM). Repeat after 30–60 minutes if needed. OR Lorazepam 4 mg (IM), stat. Repeat after 30–60 minutes if needed Pharmacological Treatment Of Schizophrenia Cont…. If haloperidol is unavailable give; Chlorpromazine 25–50 mg (deep IM). May be repeated as necessary 4 times in 24 hours. If patient is known to suffer from schizophrenia and is not neuroleptic naïve give: Zuclopenthixol acetate 50–150 mg (IM) Repeat after 2–3 days, if necessary If patient develops acute dystonia give: Promethazine deep IM 25–50 mg. In the elderly 25 mg. OR Anticholinergic agent, e.g . Biperiden , IM/IV, 2 mg. Repeat as necessary . Pharmacological Treatment Of Schizophrenia Cont…. For maintenance: Haloperidol 3-4.5 mg (PO) 12hourly OR Chlorpromazine 100–600 mg (PO) daily in divided doses 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,

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Heart Failure Basic Pharmacotherapy • Source Session/Topic 25 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 Hyponatremia: serum sodium <130 mEq/L is associated with reduced survival and may indicate worsening volume overload and/or disease progression 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

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Hypertension Basic Pharmacotherapy • Source Session/Topic 24 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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 Obesity (body mass index greater than or equal to 30 kg/m2) 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. This morbidity and mortality is related to hypertension-associated target-organ damage (e.g . 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,

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Peptic Ulcer Disease Basic Pharmacotherapy • Source Session/Topic 23 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Diabetes Mellitus Basic Pharmacotherapy • Source Session/Topic 22 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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;-

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Asthma Basic Pharmacotherapy • Source Session/Topic 21 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. 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. Positive methacholine challenge (PC 20 FEV 1 less than 12.5 mg/mL) or mannitol challenge (FEV 1 decrease of at least 15% from baseline after 635 mg or less ). 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