Cardiovascular drugs 1.

Anti hypertensive drugs Anti hypertensive drugs include: (1) Diuretics, which lower blood pressure by depleting the body of sodium and reducing blood volume and perhaps by other mechanisms. (2) Sympathoplegic agents, which lower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling in capacitance vessels. (The latter two effects reduce cardiac output.). (3) Direct vasodilators, which reduce pressure by relaxing vascular smooth muscle, thus dilating resistance vessels andto varying degreesincreasing capacitance as well. (4) Agents that block production or action of angiotensin and thereby reduce peripheral vascular resistance and (potentially) blood volume. Sympathoplegic agents: a.Centrally Acting Sympathoplegic Drugs: Mechanism of action: These agents reduce sympathetic outflow from vasopressor centers in the brainstem. E.g. methyldopa and clonidine. (3) Direct vasodilators, which reduce pressure by relaxing vascular smooth muscle, thus dilating resistance vessels andto varying degreesincreasing capacitance as well. (4) Agents that block production or action of angiotensin and thereby reduce peripheral vascular resistance and (potentially) blood volume. In fact, methyldopa's antihypertensive action appears to be due to stimulation of central alpha adrenoceptors by alpha-methylnorepinephrine or alpha methyl dopamine. Clonidine s stimulate alpha 2 receptor in the brain. Toxicity:

Methyldopa can cause nightmares, mental depression, vertigo, lactation. Clonidine cause dry mouth. B.Adrenergic NeuronBlocking Agents

These drugs lower blood pressure by preventing normal physiologic release of nor epinephrine from postganglionic sympathetic neurons for example Guanithidine and reserpine.

Guanethidine: Guanethidine inhibits the release of nor epinephrine from sympathetic nerve endings. Toxicity

Therapeutic use of guanethidine is often associated with symptomatic postural hypotension and hypotension following exercise, particularly when the drug is given in high doses, and may produce dangerously decreased blood flow to heart and brain or even overt shock. Reserpine

Reserpine, an alkaloid extracted from the roots of an Indian plant, Rauwolfia serpentine Mechanism & Sites of Action Reserpine blocks the ability of aminergic transmitter vesicles to take up and store biogenic amines. At lower doses used for treatment of mild hypertension, reserpine lowers blood pressure by a combination of decreased cardiac output and decreased peripheral vascular resistance. Toxicity

At the low doses usually administered, reserpine produces little postural hypotension. Most of the unwanted effects of reserpine result from actions on the brain or gastrointestinal tract. C.Adrenoceptor Antagonists: Beta-receptor blocking agents:

1.Non selective beta blockers: Example propranolol and nadolol, their efficacy in treating hypertension as well as most of the toxic effects results from non selective beta blockade. They decreases blood pressure primarily as a result of a decrease in cardiac output. Other beta blockers may decrease cardiac output or decrease peripheral vascular resistance to various degrees, depending on cardio selectivity and partial agonist activities. 2.Selective beta 1 blockers:

Example atenolol and bisoprolol, they decrease blood pressure as a result of a decrease in cardiac output. 3.Partial agonists: Pindolol, acebutolol, and penbutolol are partial agonists i.e beta blockers with some intrinsic sympathomimetic activity. They lower blood pressure by decreasing vascular resistance and appear to depress cardiac output or heart rate less than other beta blockers, perhaps because of significantly greater agonist than antagonist effects at 2 receptors.

Adverse effects: Bronchoconstriction. Arrhythmias.

Sexual impairment

Disturbances in metabolism: -Blockade leads to decreased glycogenolysis and decreased glucagon secretion. Fasting hypoglycemia may occur. lpha1 Blockers:

Prazosin, terazosin, and doxazosin produce most of their antihypertensive effect by selectively blocking alpha1 receptors in arterioles and venues. blockers reduce arterial pressure by dilating both resistance and capacitance vessels. Side effects:

Toxicities of the 1 blockers are relatively infrequent and mild. These include dizziness, palpitations, headache, and lassitude. Vasodilators:

Within this class of drugs are the:

a.Oral vasodilators, hydralazine and minoxidil, which are used for long-term outpatient therapy of hypertension; b.The parenteral vasodilators, nitroprusside, diazoxide, and fenoldopam, which are used to treat hypertensive emergencies; c.and the calcium channel blockers, which are used in both circumstances. Mechanism of action of vasodilators:

All of the vasodilators useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Sodium nitroprusside also relaxes veins.