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Pharmacology Lecture 8 Antihypertensive Drugs 1) List the rationale for the drug treatment of hypertension. 10-15% of the population is affected by hypertension and the lifetime probability of developing HTN is 90%. HTN, particularly systolic blood pressure, is strongly related to coronary heart disease, heart failure, stroke and peripheral arterial disease. Effective drug treatment lowers blood pressure and reduces the risk for these diseases. 2) List the classes of antihypertensive drugs available in the U.S. Diuretics – Osmotic Diuretics, Carbonic Anhydrase Inhibitors, Loop Diuretics, and Thiazide Diuretics. Adrenergic Inhibitors – Central Adrenergic Agonists, Alpha Adrenergic Antagonists, Beta Adrenergic Antagonists, and Dopamine Agonist. Vasodilators – Angiotensin Converting Enzyme (ACE) Inhibitors, Angiotensin II Receptor Antagonists, and Calcium Channel Antagonists. 3) For the prototype drugs of each class of antihypertensive drugs; describe the following: Mechanism of action, Hemodynamic effects, Adverse drug effects, Drug-drug interactions, Drug-disease interactions. Drug Class Diuretics (See Diuretic section) Central Agonists Alpha Antagonists Beta Antagonists Prototype Drug Thiozides, Furosemide, Spronolacetone, Triamterene Clonidine Central α2a recptor stimulation Block peripheral α1 adrenoreceptors Non-selective β receptor blockade Cardioselective β1 receptor blockade Hemodynamic Effects Early drop in CO due to ↓volume Peripheral resistance decreased ↓ CO, ↓ systemic vascular resistance ↓ systemic vascular resistance ↓ Heart rate and contractility, ↑ systemic vascular resistance Hydralazine Relax vascular smooth muscle ? ↓ systemic vascular resistance Minoxidil Vasodilation - ↑ K+ channel hyperpolarize SM Causes NO release, relaxes SM Inhibits ACE - ↓ angiotensin II, ↑ bradykinin ↓ systemic vascular resistance Losartan Blocks angiotensin II receptor binding Vasodilation w/↓ preload ↓afterload Verapamil, diltiazem, nifedipine Fenoldopam Bind Ca2+ channels ↓ Ca2+ for muscle contraction Dopamine (DA) 1 agonist Vasodilation Prazosin Propranolol Metoprolol Vasodilators ACE Inhibitors Angiotensin II receptor Antagonists Calcium Channel Antagonists Dopamine Agonist Na+ nitroprusside Captopril Mechanism of Action Negative salt and water balance, ↑PGI2 synthesis & action, vasodilaton ↓ cardiac preload and afterload ↓ systemic vascular resistance and preload ↑ renal blood flow ↑Na+ excretion Adverse Drug Effects Fluid and electrolyte imbalance, particularly hypokalemia with thiazides and loop diuretics Short ½life. Missed dose = rebound HTN Orthostatic HTN w/1st dose. Give 1st HS. Bad dreams, depression Cardio – worsen CHF and occlusive peripheral vascular disease (OPVD) Lungs – bronchospasm Immuno – lupus like Sx Cardio - ↑ HR use β block Cardio - ↑ HR use β block Fluid retention, Hypertrichosis Hypotension, cyanide and thiocyanate poisoning HTN w/1st dose, Cough & angioedema w/↑ kinin, renal insufficiency, hyperkalemia, proteinurea Unkown (no cough) Constipation, peripheral edema, worsen CHF, headache Drug-Drug Interactions Drug-Disease Interactions May interact w/CCBs or digoxin causing A-V block Asthma, COPD, severe heart failure, OPVD, high° A-V block Kidney or liver disease Pregnancy Pregnancy Digoxin, β blockers = A-V block Unstable angina, MI, HTN? 4) Describe the use of drugs in the management of hypertension as recommended in JNC VII report. The following tables describe the recommended drugs for the management of hypertension. The first table gives BP values and their corresponding treatments while the second table gives conditions with compelling indications and the recommended drugs for each condition. BP classification Normal PreHypertension Stage 1 Hypertension Systolic BP, mmHg <120 and 120-130 or Diastolic BP, mmHg <80 80-89 Lifestyle Modification Encourage Yes Without Compelling Indication With Compelling Indications Drug(s) for the compelling indications 140-159 or 90-99 Yes Drug(s) for the compelling indications Other antihypertensive drugs diuretics, ACE inhibitor, ARB, β-blocker, CCB as needed. Stage 2 ≥160 or ≥100 Yes 2-Drug combination for most Drug(s) for the compelling Hypertension (usually thiazide-type diuretic indications and ACE inhibitor, or ARB or Other antihypertensive drugs β-blocker or CCB) diuretics, ACE inhibitor, ARB, β-blocker, CCB as needed. Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CCB, calcium channel blocker. Condition Heart Failure Post-MI High coronary disease risk Diabetes Chronic Kidney Disease Recurrent stroke prevention Diuretic ☺ Β-Blocker ☺ ☺ ☺ ☺ ☺ ☺ ☺ No antihypertensive drug indicated Thiazide-type diuretics for most; may condsider ACE inhibitor, β-blocker, CCB or combination ACE Inhibitor ☺ ☺ ☺ ☺ ☺ ☺ ARB ☺ CCB ☺ ☺ ☺ ☺ Aldosterone Antagonist ☺ ☺
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