{"id":6558,"date":"2024-11-16T13:32:26","date_gmt":"2024-11-16T13:32:26","guid":{"rendered":"https:\/\/workhouse.sweetdishy.com\/?p=6558"},"modified":"2024-11-16T13:44:11","modified_gmt":"2024-11-16T13:44:11","slug":"antihypertensive-drugs","status":"publish","type":"post","link":"https:\/\/workhouse.sweetdishy.com\/index.php\/2024\/11\/16\/antihypertensive-drugs\/","title":{"rendered":"Antihypertensive drugs"},"content":{"rendered":"\n<p><strong>a. General consideration:-<\/strong><br>Hypertension is defined as an elevation of arterial blood pressure above an arbitrarily defined<br>normal value. The American Heart Association defines hypertension as arterial blood pressure<br>higher than 140\/90mmHg (based on three measurements at different times).<br>Hypertension may be classified in to three categories, according to the level of diastolic blood<br>pressure:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Mild hypertension with a diastolic blood pressure between 95-105 mmHg<\/li>\n\n\n\n<li>Moderate hypertension with a diastolic blood pressure between 105 \u2013 115mmHg<\/li>\n\n\n\n<li>Severe hypertension with a diastolic blood pressure above 115mmHg.<br>52<br>Sustained arterial hypertension damages blood vessels in kidney, heart and brain and leads to<br>an increased incidence of renal failure, cardiac failure, and stroke.<br>Effective pharmacologic lowering of blood pressure prevents the damage to blood vessels and<br>reduces the morbidity and mortality rate.<br>In order to understand the pathophysiology of hypertensive states and, in turn, the underlying<br>rationale of drug therapy, an appreciation of the systems normally involved in monitoring and<br>regulating blood pressure is required.<br>Two factors which determine blood pressure are cardiac out put (stroke volume x heart rate)<br>and total peripheral resistance of the vasculature. Blood pressure is regulated by an interaction<br>between nervous, endocrine and renal systems<br>Elevated blood pressure is usually caused by a combination of several abnormalities such as<br>psychological stress, genetic inheritance, environmental and dietary factors and others.<br>Patients in whom no specific cause of hypertension can be found are said to have essential<br>hypertension or primary hypertension (accounts for 80-90 % of cases).<br>Secondary hypertension arises as a consequence of some other conditions such as,<br>atherosclerosis, renal disease, endocrine diseases and others. The central issue of<br>antihypertensive therapy is to lower arterial blood pressure, irrespective of the cause.<br>The choice of therapy of a patient with hypertension depends on a variety of factors: age, sex,<br>race, body build, life-style of the patient, cause of the disease, other co-existing disease, rapidity<br>of onset and severity of hypertension, and the presence or absence of other risk factors for<br>cardiovascular disease (e.g. smoking, alcohol consumption, obesity, and personality type).<\/li>\n\n\n\n<li><br><strong>b. Antihypertensive therapies.<\/strong><\/li>\n<\/ul>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Non pharmacological therapy of hypertension<br>Several non-pharmacological approaches to therapy of hypertension are available. These<br>include:<\/li>\n<\/ol>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Low sodium chloride diet<\/li>\n\n\n\n<li>Weight reduction<\/li>\n\n\n\n<li>Exercise<\/li>\n\n\n\n<li>Cessation of smoking<\/li>\n\n\n\n<li>Decrease in excessive consumption of alcohol<br>53<\/li>\n\n\n\n<li>Psychological methods (relaxation, meditation \u2026etc)<\/li>\n\n\n\n<li>Dietary decrease in saturated fats.<br>The sensitivity of patients differs to these non-pharmacological approaches, but, on the<br>average, only modest reductions (5 to 10 mmHg) in blood pressure can be achieved. This may<br>be sufficient for the treatment of some mild hypertensive cases.<br>The major advantage of non-pharmacological approaches is the relative safety and freedom<br>from side effects, compared with drug therapy.<\/li>\n<\/ul>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Pharmacological therapy of hypertension.<br>Most patients with hypertension require drug treatment to achieve sustained reduction of blood<br>pressure. Currently available drugs lower blood pressure by decreasing either cardiac output<br>(CO) or total peripheral vascular resistance (PVR) or both although changes in one can<br>indirectly affect the other. However, physiological mechanisms tend to oppose a drug \u2013 induced<br>reduction of blood pressure.<br>Anti &#8211; hypertensive drugs are classified according to the principal regulatory site or mechanism<br>on which they act. They include:<br>A) Diuretics, which lower blood pressure by depleting the body sodium and reducing blood<br>volume. Diuretics are effective in lowering blood pressure by 10 \u2013 15 mmHg in most<br>patients.<\/li>\n\n\n\n<li><br><strong>Diuretics include:<\/strong><br>a) Thiazides and related drugs, e.g. hydrochlorthiazide bendrofluazide, chlorthalidone, etc.<br>Initially, thiazide diuretics reduce blood pressure by reducing blood volume and cardiac out put<br>as a result of a pronounced increase in urinary water and electrolyte particularly sodium<br>excretion.<br>With chronic administration (6-8weeks), they decrease blood pressure by decreasing peripheral<br>vascular resistance as the cardiac out put and blood volume return gradually to normal values.<br>Thiazides are appropriate for most patients with mild or moderate hypertension and normal<br>renal and cardiac function.<br>b) Loop diuretics, e.g. furosemide, ethacrynic acid, etc.<br>Loop diuretics are more potent than thiazides as diuretics. The antihypertensive effect is mainly<br>due to reduction of blood volume.<br>54<br>Loop diuretics are indicated in cases of severe hypertension which is associated with renal<br>failure, heart failure or liver cirrhosis.<br>c) Potassium sparing diuretics, e.g. spironolactone<br>They are used as adjuncts with thiazides or loop diuretics to avoid excessive potassium<br>depletion and to enhance the natriuretic effect of others. The diuretic action of these drugs is<br>weak when administered alone.<br>B) Sympathoplegic agents (Depressants of sympathetic activity).<br>Based on the site or mechanism of action sympathoplegic drugs are divided into:<br>a) Centrally acting antihypertensive agents e.g. methyldopa, clonidine<br>Centrally acting sympathetic depressants act by stimulating \u03b12 &#8211; receptors located in the<br>vasomotor centre of the medulla. As a result, sympathetic out flow from the medulla is<br>diminished and either total peripheral resistance or cardiac out put decreases. . Methyldopa<br>is useful in the treatment mild to moderately severe hypertension.<br>Methyldopa is a prodrug and must be converted in the CNS to active \u03b1 &#8211; methylnorepinephrine<br>to exert the effect on blood pressure.<br>The side effects of methyldopa include sedation, vertigo, dry mouth, nausea, vomiting, diarrhea,<br>postural hypotension, impotence, haemolytic anemia, weight gain and hypersensitivety<br>reactions (fever, liver damage, thrombocytopenia).<br>b) Adrenoceptor antagonists, e.g propranolol (beta blocker), prazosin (alpha blocker), labetalol<br>(alpha and beta blocker).<br>\u03b2 \u2013 Blockers antagonize beta, receptors located on the myocardium and prevent the cardio<br>acceleration, which follows sympathetic stimulation.<br>The rate and force of myocardial contraction is diminished, decreasing cardiac out put and thus,<br>lowering blood pressure. An additional effect which can contribute to a reduction of blood<br>pressure is that renin release is mediated by \u03b2 receptors. Therefore, receptor blockade prevents<br>angiotensin II formation and associated aldosterone secretion, resulting in a decrease in total<br>peripheral resistance and blood volume.<br>The principal action of alpha adrenergic blocking drugs is to produce peripheral vasodilation.<br>55<br>Alpha blockers reduce arterial pressure by dilating both resistance and capacitance vessels.<br>Treatment with prazosin should be initiated with low dose (1mg 3 times daily) to prevent<br>postural hypotension and syncope or be given at bed time.<br>c) Adrenergic neuron \u2013 blocking agents, e.g. guanethidine<br>Guanethidine is an adrenergic neuron-blocking drug recommended for treatment of severe<br>forms of hypertension.<br>Guanethidine blocks adrenergic nerve transmission, preventing the release of transmitter.<br>It lowers blood pressure by reducing both cardiac out put and total peripheral resistance.<br>d) Drugs which deplete catecholamine stores, e.g. reserpine.<br>Reserpine interferes with the storage of endogenous catecholamines in storage vesicles<br>as a result of which little neurotransmitter is released upon stimulation. It leads to<br>reduction of cardiac out put and peripheral vascular resistance. Reserpine is a second-line<br>drug for treatment of hypertension.<br>e) Ganglion blockers, e.g. trimethaphan<br>Trimethaphan is ganglion blocking drug which is reserved for use in hypertensive emergencies<br>only.<br>C) Direct vasodilators. These include:-<\/li>\n<\/ol>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Arterial vasodilators, e.g. hydralazine<\/li>\n\n\n\n<li>Arteriovenous vasodilators, e.g. sodium nitroprusside<\/li>\n\n\n\n<li><br><strong>Hydralazine:<\/strong> It dilates arterioles but not veins. It is used particularly in severe hypertension.<br>The most common adverse effects are headache, nausea, anorexia, palpitations, sweating and<br>flushing which are typical to vasodilators.<\/li>\n\n\n\n<li><br><strong>Sodium nitroprusside: <\/strong>It is a powerful vasodilator that is used in treating hypertensive<br>emergencies as well as severe cardiac failure.<br>It dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance<br>and venous return.<br>Nitroprusside rapidly lowers blood pressure and it is given by intravenous infusion.<br>The most serious toxicities include metabolic acidosis, arrhythmias, excessive hypotension and<br>death.<br>56<br>D) Angiotensin converting enzyme inhibitors, e.g. captopril, enalapril, etc. The prototype is<br>captopril. Captopril inhibits angiotensin converting enzyme that hydrolyzes angiotensin I<br>(Inactive) to angiotensin II (Active), a potent vasoconstrictor, which additionally stimulates<br>the secretion of aldosterone. It lowers blood pressure principally by decreasing peripheral<br>vascular resistance.<br>The adverse effects include maculopapular rash, angioedema, cough, granulocytopenia and<br>diminished taste sensation.<br>Enalapril is a prodrug with effects similar to those of captopril.<br>E) Calcium channel blockers, e.g. nifedipine, verapamil, nicardipine, etc.<br>The prototype is verapamil.<br>The mechanism of action in hypertension is inhibition of calcium influx in to arterial smooth<br>muscle cells, resulting in a decrease in peripheral resistance.<br>Verapamil has the greatest cardiac depressant effect and may decrease heart rate and cardiac<br>out put as well.<br>The most important toxic effects for calcium channel blockers are cardiac arrest, bradycardia,<br>atrioventricular block and congestive heart failure.<\/li>\n\n\n\n<li><br><strong>Lines of treatment of primary hypertension<\/strong><br>The initial step in treating hypertension may be non-pharmacologic. Dietary salt restriction may<br>be effective treatment for about half of the patients with mild hypertension. Weight reduction<br>even without salt restriction normalizes blood pressure in up to 70% of obese patients with mild<br>to moderate hypertension. Regular exercise may also be helpful in some hypertensive patients.<br>When non-pharmacologic approaches do not satisfactorily control blood pressure, drug therapy<br>begins in addition to non-pharmacological approaches.<br>The selection of drug(s) depends on various factors such as the severity of hypertension,<br>patient factors (age, race, coexisting diseases, etc.).<br>For most patients with mild hypertension and some patients with moderate hypertension monotherapy with either of the following drugs can be sufficient.<\/li>\n\n\n\n<li>Thiazide diuretics<\/li>\n\n\n\n<li>Beta blockers<\/li>\n\n\n\n<li>Calcium channel blockers<br>57<\/li>\n\n\n\n<li>Angiotensin converting enzyme inhibitors<\/li>\n\n\n\n<li>Central sympathoplegic agents<br>Beta-blockers are preferred in young patients, high renin hypertension and patients with<br>tachycardia or angina and hypertension. Black patients respond well to diuretics and calcium<br>channel blockers than to beta-blockers and ACE inhibitors.<br>If mono-therapy is unsuccessful, combination of two drugs with different sites of action may be<br>used. Thiazide diuretics may be used in conjunction with a beta-blocker, calcium channel<br>blocker or an angiotensin converting enzyme inhibitor.<br>If hypertension is still not under control, a third drug e.g. vasodilator such as hydralazine may be<br>combined.<br>When three drugs are required, combining a diuretic, a sympathoplegic agents or an ACE<br>inhibitor, and a direct vasodilator or calcium channel block is effective.<br>The treatment of hypertensive emergencies is usually started with furosemide given by<br>parenteral route at dose of 20-40mg. In addition, parenteral use of diazoxide, sodium<br>nitroprusside, hydralazine, trimethaphan, labetalol can be indicated.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>a. General consideration:-Hypertension is defined as an elevation of arterial blood pressure above an arbitrarily definednormal value. The American Heart Association defines hypertension as arterial blood pressurehigher than 140\/90mmHg (based on three measurements at different times).Hypertension may be classified in to three categories, according to the level of diastolic bloodpressure:<\/p>\n","protected":false},"author":1,"featured_media":6503,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[691],"tags":[],"class_list":["post-6558","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cardiovascular-renal-drugs"],"jetpack_featured_media_url":"https:\/\/workhouse.sweetdishy.com\/wp-content\/uploads\/2024\/11\/heart.png","_links":{"self":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts\/6558","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/comments?post=6558"}],"version-history":[{"count":2,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts\/6558\/revisions"}],"predecessor-version":[{"id":6563,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/posts\/6558\/revisions\/6563"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/media\/6503"}],"wp:attachment":[{"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/media?parent=6558"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/categories?post=6558"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/workhouse.sweetdishy.com\/index.php\/wp-json\/wp\/v2\/tags?post=6558"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}