PST NTA Level 6

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 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 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 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 Breast Cancer Basic Pharmacotherapy • Source Session/Topic 31 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 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?

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Prostate Cancer Basic Pharmacotherapy • Source Session/Topic 32 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 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 … Low risk: T1–T2a and PSA < 10 ng/ml and GS ≤ 6 Intermediate risk: T2b or PSA 10 – 20 ng/ml or GS 7 High risk: T2c–T4 or PSA > 20ng/ml or GS 8–10 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 Docetaxel, 75 mg/m2 every 3 weeks up to 6 cycles, combined with prednisone, 5 mg twice daily, improves survival in castrate-refractory prostate cancer. It is mainly reserved for hormonal-refractory prostate cancer. The most common adverse events include nausea, alopecia, and myelosuppression. Cabazitaxel 25 mg/m2 every 3 weeks with prednisone 10 mg daily significantly improves progression-free and overall survival. 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

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Oropharyngeal Candidiasis Basic Pharmacotherapy • Source Session/Topic 33 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 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,