Pathology Section B (A) Define hypertension. (B) State five complications of systemic hypertension. (C) Briefly explain the effect of hypertension on atherosclerosis. A) State 5 risk factors of myocardial infarction. B) List 5 complications of myocardial infarction Pharmacology Explain how Nitroprusside causes cyanide toxicity and describe some of the manifestations. Mention 2 antidotes and explain how each helps in the toxicity. Explain 3 recommendations you would make to a young house officer who wants to reduce nitroprusside toxicity and ensure safety of the patient. Que: List 2 classes of drugs you would recommend for: a. Stable angina b. Variant angina For each class, list 3 examples of drugs Discuss the pharmacological relevance of each of the classes as it relates to the type of angina.

Pathology 1. (A) Define hypertension. Hypertension is defined as persistently elevated systemic arterial blood pressure, typically measured as a systolic pressure of 130 mmHg or higher, or a diastolic pressure of 80 mmHg or higher. 1. (B) State five complications of systemic hypertension. 1. Atherosclerosis 2. Left ventricular hypertrophy (leading to heart failure) 3. Stroke (ischemic or hemorrhagic) 4. Kidney disease (hypertensive nephrosclerosis) 5. Retinopathy 1. (C) Briefly explain the effect of hypertension on atherosclerosis. Hypertension damages the endothelial lining of blood vessels, making them more permeable to lipids and inflammatory cells. This damage promotes the formation and progression of atherosclerotic plaques by creating areas where cholesterol can accumulate and harden, narrowing the arteries and increasing the risk of blockages. A) State 5 risk factors of myocardial infarction. 1. Hypertension 2. Hyperlipidemia (high cholesterol) 3. Diabetes mellitus 4. Smoking 5. Family history of premature coronary artery disease B) List 5 complications of myocardial infarction. 1. Arrhythmias (e.g., ventricular fibrillation) 2. Heart failure 3. Cardiogenic shock 4. Ventricular aneurysm 5. Pericarditis (Dressler's syndrome) Pharmacology 1. Explain how Nitroprusside causes cyanide toxicity and describe some of the manifestations. Nitroprusside is metabolized in the body by reacting with hemoglobin, releasing nitric oxide (NO) and five cyanide ions (CN⁻). These cyanide ions are normally converted to thiocyanate by the enzyme rhodanese, using thiosulfate as a sulfur donor. However, if nitroprusside is administered rapidly or in high doses, the body's capacity to detoxify cyanide can be overwhelmed, leading to an accumulation of cyanide. Cyanide inhibits cytochrome c oxidase in the mitochondrial electron transport chain, preventing cellular respiration and leading to histotoxic hypoxia. Manifestations include: • Metabolic acidosis (lactic acidosis) • Tachycardia • Altered mental status (confusion, seizures, coma) • Arrhythmias • Hypotension 2. Mention 2 antidotes and explain how each helps in the toxicity. 1. Sodium thiosulfate: This antidote provides an exogenous sulfur donor, enhancing the activity of the enzyme rhodanese. Rhodanese converts cyanide (CN⁻) into less toxic thiocyanate (SCN⁻), which can then be excreted by the kidneys. 2. Hydroxocobalamin: This antidote directly binds to cyanide ions, forming cyanocobalamin (vitamin B₁₂), which is a non-toxic compound that can be safely excreted in the urine. It does not require an enzymatic pathway for detoxification. 3. Explain 3 recommendations you would make to a young house officer who wants to reduce nitroprusside toxicity and ensure safety of the patient. 1. Use the lowest effective dose and shortest duration: Administer nitroprusside at the minimum effective dose and for the shortest possible time to achieve the therapeutic goal, reducing the total cyanide load. 2. Monitor blood cyanide levels: Regularly check blood cyanide levels, especially in patients receiving high doses, prolonged infusions, or those with renal impairment, to detect accumulation early. 3. Co-administer sodium thiosulfate: Consider prophylactic co-administration of sodium thiosulfate, particularly in patients at high risk for toxicity, to enhance cyanide detoxification and prevent accumulation. Que: Angina 1. List 2 classes of drugs you would recommend for: a. Stable angina 1. Beta-blockers 2. Calcium channel blockers (non-dihydropyridines or dihydropyridines) b. Variant angina 1. Calcium channel blockers 2. Nitrates 1. For each class, list 3 examples of drugs a. Stable angina Beta-blockers: 1. Metoprolol 2. Atenolol 3. Carvedilol Calcium channel blockers: 1. Amlodipine 2. Diltiazem 3. Verapamil b. Variant angina Calcium channel blockers: 1. Nifedipine 2. Diltiazem 3. Verapamil Nitrates: 1. Nitroglycerin 2. Isosorbide dinitrate 3. Isosorbide mononitrate Discuss the pharmacological relevance of each of the classes as it relates to the type of angina. Stable Angina: Beta-blockers: These drugs reduce myocardial oxygen demand by decreasing heart rate, myocardial contractility, and blood pressure. By slowing the heart and reducing the force of contraction, they allow the heart to work less, thus preventing ischemia during exertion. Calcium channel blockers: These drugs reduce myocardial oxygen demand by causing vasodilation (reducing afterload) and, for non-dihydropyridines, by decreasing heart rate and contractility. They also increase myocardial oxygen supply by dilating coronary arteries. Variant Angina (Prinzmetal's Angina): Calcium channel blockers: These are the first-line treatment for variant angina. They prevent and reverse coronary artery spasm by blocking calcium influx into vascular smooth muscle cells, leading to coronary vasodilation and increased myocardial oxygen supply. Nitrates: These drugs cause generalized vasodilation, including dilation of coronary arteries, which helps to relieve and prevent coronary spasms. They also reduce preload and afterload, decreasing myocardial oxygen demand, but their primary role in variant angina is spasm relief. Got more? Send 'em 📸