Introductory Clinical Pharmacology Chapter 41 Antihypertensive Drugs

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1 Introductory Clinical Pharmacology Chapter 41 Antihypertensive Drugs

2 Blood Pressure Normal = sys<120 and diastolic <80 Prehypertension /80-89 Stage 1 hypertension / Stage 2 hypertension >159 or >99 For every 20mmgh increase in systolic BP from ages 40-69, mortality from ischemic heart disease and stroke doubles.

3 Blood Pressure BP= CO x SVR Vascular resistance influenced by alpha1 receptors (norepinepherine), calcium channels, AT2 receptors (RAAs vasoconstriction and sodium and water retention w/potassium excreteion CO= HR x SV Stroke volume=preload (aldosterone) HR influenced by β1 receptors

5 Blood Pressure Force of blood against arterial walls Normal: <120/<80 Hypertension Essential vs. secondary Increases risk of heart disease, CHF, RF, blindness, stroke African Americans twice as likely as Caucasians Essential cannon be cured but can be controlled

6 Non-Pharmacologic Control of HTN Weight loss Stress reduction Smoking cessation Regular aerobic exercise Decrease sodium and sugar intake Increase potassium intake DASH diet

7 Antihypertensive Drugs ACE inhibitors: captopril, enalapril, lisinopril ARBs: Losartan, valsartan Nitrates: nitroglycerin, isosorbide dinitrate Calcium channel blockers: verapamil, nifedipine, diltiazem Alpha adrenergic blockers: phentolamine, phenoxybenzamine, prazosin, terazosin Adrenergic neuron blockers: reserpine, guanethidine, guanadrel Centrally acting agents: clonidine, guanabenz, methyldopa Other: hydralazine, minoxidil, nitroprusside,diazoxide, nesiritide

8 Pharmacologic control of BP Diuretics decrease preload Beta Blockers (-lols)decrease contractile state of the heart and heart rate (decrease cardiac output) ACE inhibitors (-prils) Block AT2 via ACE inhibition ARBs ( sartans) block AT2 receptors Calcium Channel blockers (dipines and others) block calcium channels on peripheral vessels Alpha 1 Blockers (-osins) are rarely used for HTN Alpha 2 agonists (catapres) work in hypothalamus Other: hydralazinie, nitroprusside, morphine, NTG: direct vasodilators for hypertensive crises

9 Vasodilators May dilate arterioles, veins or both Uses: essential hypertension, hypertensive crisis, angina, heart failure, MI, production of controlled hypotension during surgery Adverse effects: postural hypotension, reflex tachycardia, expansion of blood volume

10 Hydralazine (Apresoline) Selective dilation of arterioles peripheral resistance, BP, HR, myocardial contractility Used for Essential HTN, usually in conjunction with a β- blocker and a diuretic; hypertensive crisis, heart failure Adverse effects: reflex tachycardia, Increased blood volume, SLE like syndrome, headache, dizziness, weakness, fatigue Use with β-blocker prevents reflex tachycardia, diuretics prevent blood volume expansion

11 Renin-Angiotension-Aldosterone System

12 Ace Inhibitors Benazepril, captopril, enalapril, lisinopril, ramipril, fosinopril Prevent conversion of Angiotensin I to Angiotensin II Use: hypertension, HF, diabetic neuropathy, MI. Prevention of adverse CV events in patients at risk Excreted by the kidneys. Dosages must be reduced in patients with kidney disease. SE: Hypotension, hyperkalemia, hypoglycemia, cough, angioedema

13 Angiotensin Receptor Blockers Losartan, valsartan, candesartan irbesartan telmisartan, olmesartan Action of the angiotensin II receptor antagonists: Block the binding of angiotensin II at the receptor sites found in smooth muscle and adrenal gland; this stops renin angiotensin system and lowers blood pressure Uses: Used for the treatment of hypertension; some drugs are used only in severe cases of hypertension; two antihypertensive drugs may be given together to achieve a better response

14 Antihypertensive Drugs: Contraindications Antihypertensive drugs are contraindicated in patients with known hypersensitivity to the individual drug ACEIs: Contraindicated in patients with impaired renal function, congestive heart failure, salt or volume depletion, bilateral stenosis, or angioedema, also during pregnancy or lactation Use of the ACEIs and the angiotensin II receptor blockers during the second and third trimester of pregnancy is contraindicated because use may cause fetal or neonatal injury or death

15 Beta Blockers Acebutolol, atenolol, carvedilol, esmolol, labetalol, bisoprolol, metoprolol, bisoprolol Epinepherine stimulates β1 receptors on heart HR BP and increases strength of contraction Β2 stimulation causes tremors, bronchodilation vasodilation of large arteries in legs. Non-selective β-blockers affect heart, skeletal muscle, lungs and arteries (propranolol, nadolol, timolol, carvedilol, pindolol) Β1 selective blockers block receptors on heart so that heart rate falls, blood pressure falls, cardiac workload decreases. (atenolol, metoprolol, betaxolol, bisoprolol)

16 Uses of Beta-blockers Decrease palpitations during panic attacks Decrease essential tremors Decrease situational anxiety

17 Beta1 Agonists Stimulate β1 receptors to increase HR and contractility Dobutamine Dopamine Levophed

18 Calcium Channel Blockers Class 1: Verapamil Blocks calcium channels primarily on the coronary vessels and AV node Increases blood flow to heard and decreases impulses through AV node. Used to decrease workload of heart, slows rate, treat HTN, angina, afib Class 2 Diltiazem Dilates calcium channels on the coronary and peripheral vessels Uses: a fib, HTN, angina, vasospasm

19 Class 3 Calcium Channel Blockers -dipines: amlodipine, felodipine, nifedipine, Peripheral vessel calcium channel blockers Uses: HTN, vasospasm (Prinzmetals s angina, Reynaud s) SE: Verapamil causes significant consipation, diltiazem less Dipines: headaches, hypotension, peripheral and pedal edema

20 True/False 1. Blood pressure is the force of the blood against the walls of the arteries. 2. A hypertensive emergency is a case of extremely high blood pressure in which blood pressure must be lowered immediately to prevent damage to the target organs. 3. Risk factors for hypertension include diabetes, obesity, smoking and family history of CVD. 4. A systolic pressure of less than 120 mmhg and a diastolic pressure of less than 80 mmhg (120/80) are considered abnormal. 5. The hypotensive effects of most antihypertensive drugs are increased when administered with diuretics and other antihypertensives. Fill-in-the-Blank 1. is defined as a systolic pressure between 120 and 139 mmhg or a diastolic pressure between 80 and 89 mmhg. 2. When a direct cause of the hypertension can be identified, the condition is described as hypertension. 3. promotes the retention of sodium and water, which may contribute to a rise in blood pressure. 4. hypotension occurs when the individual has a significant drop in blood pressure (usually 10 mmhg systolic or more) when assuming an upright position. 5. Nitroprusside and diazoxide are drugs used to treat patients with a emergency.

Antihypertensives. Antihypertensive Classes. RAAS Inhibitors. Renin-Angiotensin Cascade. Angiotensin Receptors. Approaches to Hypertension Treatment

Antihypertensives. Antihypertensive Classes. RAAS Inhibitors. Renin-Angiotensin Cascade. Angiotensin Receptors. Approaches to Hypertension Treatment Approaches to Hypertension Treatment Antihypertensives Inhibit Sympathetic impulses Inhibit contractility Inhibit heart rate Inhibit vasoconstriction Inhibit smooth muscle function Inhibit RAAS Inhibit