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Anti Hypertensive Anti Hypertensive Agents.Agents.

Dr. Aisha AL-GhamdiDr. Aisha AL-Ghamdi

Associate professorAssociate professor

Consultant internistConsultant internist

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AntihypertensivesAntihypertensives are a class of are a class of drugsdrugs that that are used in are used in medicinemedicine and and pharmacologypharmacology to to treat treat hypertensionhypertension..

Evidence suggests that reduction of the Evidence suggests that reduction of the blood pressureblood pressure by 5-6 mmHg can decrease by 5-6 mmHg can decrease the risk of the risk of Stroke by 40%, Coronary heart Stroke by 40%, Coronary heart disease by15-20%disease by15-20% and reduces the and reduces the likelihood of dementia, heart failure, and likelihood of dementia, heart failure, and mortality from cardiovascular disease. mortality from cardiovascular disease.

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Antihypertensive groupsAntihypertensive groups

Diuretics.Diuretics. Adrenergic receptor antagonists.Adrenergic receptor antagonists. Adrenergic receptor agonist.Adrenergic receptor agonist. Calcium channel blockers.Calcium channel blockers. Angiotensin-converting enzyme inhibitors.Angiotensin-converting enzyme inhibitors. Angiotensin II receptor antagonists.Angiotensin II receptor antagonists. Aldosterone antagonists.Aldosterone antagonists. Vasodilators.Vasodilators. Centrally acting adrenergic drugs. Centrally acting adrenergic drugs.

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DIURETICSDIURETICS

help the kidneys eliminate excess salt and help the kidneys eliminate excess salt and water from the body's tissues and blood.water from the body's tissues and blood.

Loop diuretics:Loop diuretics: bumetanidebumetanide ethacrynicethacrynic acid acid furosemidefurosemide torsemidetorsemide

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CONT.CONT.

Thiazide diureticsThiazide diuretics chlortalidonechlortalidone epitizideepitizide hydrochlorothiazidehydrochlorothiazide and and chlorothiazidechlorothiazide bendroflumethiazidebendroflumethiazide

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CONT.CONT. Thiazide-like diuretics: Thiazide-like diuretics: indapamideindapamide chlorthalidonechlorthalidone metolazonemetolazone

Potassium-sparing diuretics:Potassium-sparing diuretics: amilorideamiloride triamterenetriamterene spironolactonespironolactone

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CONT.CONT.

Only the Only the thiazidethiazide and thiazide-like diuretics and thiazide-like diuretics have good evidence of beneficial effects have good evidence of beneficial effects on important endpoints of on important endpoints of hypertensionhypertension, , and hence, should usually be the 1st and hence, should usually be the 1st choice when selecting a diuretic to treat choice when selecting a diuretic to treat hypertension hypertension

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CONT.CONT.

The reason why thiazides-type diuretics are The reason why thiazides-type diuretics are better than the others is because of better than the others is because of

1.1. Their vasodilating properties.Their vasodilating properties.

2.2. The diuretic effect of thiazides may be The diuretic effect of thiazides may be apparent shortly after administration.apparent shortly after administration.

3.3. The full anti-hypertensive effect to The full anti-hypertensive effect to develop.takes longer (weeks of develop.takes longer (weeks of treatment). treatment). {disadvantage !!}{disadvantage !!}

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Adverse effects of thiazides ;Adverse effects of thiazides ;

1.1. Hypokalemia → arrhythmias Hypokalemia → arrhythmias 2.2. Hyperuricaemia → acute gout.Hyperuricaemia → acute gout.3.3. increase serum LDL- cholesterol and TG. increase serum LDL- cholesterol and TG. 4.4. Impair glucose tolerance and increase insulin Impair glucose tolerance and increase insulin

resistance. Reports of frank diabetes are rare. resistance. Reports of frank diabetes are rare. Although thiazides probably should be avoided Although thiazides probably should be avoided as first-line drugs in patients with diabetes and as first-line drugs in patients with diabetes and hyperlipidaemia. hyperlipidaemia.

5.5. Rarer side effects include nausea, headache, Rarer side effects include nausea, headache, rashes, photosensitivity and blood dyscrasias. rashes, photosensitivity and blood dyscrasias.

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Adrenergic receptor antagonistsAdrenergic receptor antagonists

Beta blockers;Beta blockers; (no longer 1st line therapy in many countries)(no longer 1st line therapy in many countries)

atenololatenolol, , metoprololmetoprolol, , nadololnadolol, , oxprenololoxprenolol, , pindololpindolol, , propranololpropranolol, , timololtimolol..

Alpha blockers;Alpha blockers; DoxazosinDoxazosin, , phentolaminephentolamine, , indoraminindoramin, ,

phenoxybenzaminephenoxybenzamine, , prazosinprazosin , ,terazosinterazosin, , tolazolinetolazoline. .

Mixed Alpha + Beta blockers;Mixed Alpha + Beta blockers;bucindololbucindolol, , carvedilolcarvedilol, , labetalollabetalol..

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beta-receptorbeta-receptor

Types →ßTypes →ß11 ß ß22 ß ß33

Vasodilation (b2) Vasodilation (b2)   Cardioacceleration (b1) Cardioacceleration (b1)   Intestinal relaxation (b2) Intestinal relaxation (b2)   Uterus relaxation(b2) Uterus relaxation(b2)   Bronchodilation (b2) Bronchodilation (b2)

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Adverse effects of b-blockers;Adverse effects of b-blockers;

slow the rate of conduction at the atrio-slow the rate of conduction at the atrio-ventricular node.ventricular node.

Sinus bradycardia is common and is not a Sinus bradycardia is common and is not a reason to stop beta-blockers unless the reason to stop beta-blockers unless the patient is symptomatic or the heart rate patient is symptomatic or the heart rate falls below 40 beats/minute.falls below 40 beats/minute.

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contraindicated in;contraindicated in;

Patients with 2Patients with 2ndndand 3and 3d d degree heart block.degree heart block. AsthmaticsAsthmatics rest ischaemia of the legs (Blockade of b rest ischaemia of the legs (Blockade of b

receptors in the peripheral circulation → receptors in the peripheral circulation → vasoconstriction)vasoconstriction)

Diabetics (theoretically, reduce the Diabetics (theoretically, reduce the awareness of low blood glucose →mask awareness of low blood glucose →mask hypoglycemic symptoms).hypoglycemic symptoms).

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Adrenergic receptor agonist.Adrenergic receptor agonist.

Alpha-2 agonistsAlpha-2 agonists

Revise (Revise (αα-receptors sites, function)-receptors sites, function) clonidineclonidine methyldopamethyldopa

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alpha-receptoralpha-receptor

Types → Types → αα11 (A,B,D) , (A,B,D) , αα2 2 (A,B,C)(A,B,C)

  Vasoconstriction Vasoconstriction   iris dilation iris dilation   intestinal relaxation intestinal relaxation   intestinal sphincter contractionintestinal sphincter contraction   bladder sphincterbladder sphincter contraction contraction

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Calcium channel blockersCalcium channel blockers

Block the entry of calcium into muscle cells in artery walls.Block the entry of calcium into muscle cells in artery walls. Dihydropyridines;Dihydropyridines;

amlodipineamlodipine felodipinefelodipine isradipineisradipine lercanidipinelercanidipine »peripheral vasodilatation→ reflex tachycardia. »peripheral vasodilatation→ reflex tachycardia. nifedipinenifedipine(Adalat®) (Adalat®) nimodipinenimodipine nitrendipinenitrendipine

Non-dihydropyridines; Non-dihydropyridines; diltiazemdiltiazem , , verapamilverapamil. . »peripheral vasodilatation+ ↓ HR .»peripheral vasodilatation+ ↓ HR .

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Adverse effects of CaCB;Adverse effects of CaCB;

Vasodilatation causes ankle oedema, Vasodilatation causes ankle oedema, headache, flushing and palpitation. Some headache, flushing and palpitation. Some of these side effects can be offset by of these side effects can be offset by combining a calcium channel blocker with combining a calcium channel blocker with a b-blocker. a b-blocker. Verapamil, Diltiazem can cause heart Verapamil, Diltiazem can cause heart block and reduces intestinal motility. block and reduces intestinal motility. significant constipation may be occurred.significant constipation may be occurred.

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ACE inhibitorsACE inhibitors

captoprilcaptopril enalaprilenalapril fosinoprilfosinopril lisinoprillisinopril perindoprilperindopril quinaprilquinapril ramiprilramipril trandopriltrandopril benzaprilbenzapril

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Adverse effects of ACEI;Adverse effects of ACEI;

Cough commonest, more in females and older Cough commonest, more in females and older patients.patients.

Angioedema more serious, but rare, which Angioedema more serious, but rare, which occurs in about 0.1 to 0.2 per cent of patients. occurs in about 0.1 to 0.2 per cent of patients.

Dramatic deterioration in renal function can Dramatic deterioration in renal function can occur in patients with bilateral renal artery occur in patients with bilateral renal artery stenosis. Serum urea and creatinine should, stenosis. Serum urea and creatinine should, therefore, be checked before and a few weeks therefore, be checked before and a few weeks after starting an ACE inhibitor. after starting an ACE inhibitor.

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Angiotensin II receptor antagonistsAngiotensin II receptor antagonists

AngiotensinAngiotensin II receptor antagonists II receptor antagonists work by work by antagonizingantagonizing the activation of the activation of angiotensinangiotensin receptors receptors..

candesartancandesartan eprosartaneprosartan irbesartanirbesartan losartanlosartan olmesartanolmesartan telmisartantelmisartan valsartanvalsartan

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Adverse effects of Adverse effects of Angiot.II R.A.Angiot.II R.A.

hyperkalaemia, renal impairment and hyperkalaemia, renal impairment and hypotension. They are almost as well hypotension. They are almost as well tolerated as placebo. Nevertheless, cases tolerated as placebo. Nevertheless, cases of angioedema have been reported with of angioedema have been reported with some of these agents. some of these agents.

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Aldosterone antagonistsAldosterone antagonists

Eplerenone. Eplerenone. Spironolactone.Spironolactone.

AldosteroneAldosterone antagonists are not antagonists are not recommended as first-line agents for blood recommended as first-line agents for blood pressure,but pressure,but spironolactonespironolactone and and eplerenoneeplerenone are both used in the treatment are both used in the treatment of of heart failureheart failure..

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VasodilatorsVasodilators

VasodilatorsVasodilators act directly on arteries to relax act directly on arteries to relax their walls so blood can move more easily their walls so blood can move more easily through them;used in through them;used in

medical emergenciesmedical emergencies.. sodium nitroprusside used in medical sodium nitroprusside used in medical

emergencies.emergencies. Hydralazine.Hydralazine.

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Centrally acting adrenergic drugsCentrally acting adrenergic drugs

ClonidineClonidine, , GuanabenzGuanabenz, , MethyldopaMethyldopa , Central , Central alpha agonists lower blood pressure by alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. open peripheral arteries easing blood flow. Central alpha agonists, such as clonidine, are Central alpha agonists, such as clonidine, are usually prescribed when all other anti-usually prescribed when all other anti-hypertensive medications have failed. For hypertensive medications have failed. For treating hypertension, these drugs are usually treating hypertension, these drugs are usually administered in combination with a diuretic.administered in combination with a diuretic.

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CONT.CONT.

Adverse effects of this class of drugs Adverse effects of this class of drugs include sedation, postural hypotension, include sedation, postural hypotension, drying of the nasal mucosa and rebound drying of the nasal mucosa and rebound hypertension.hypertension.

Some adrenergic neuron blockers are Some adrenergic neuron blockers are used for the most resistant forms of used for the most resistant forms of hypertension:hypertension:

GuanethidineGuanethidine ReserpineReserpine

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CONT.CONT.

These drugs are old antihypertensive These drugs are old antihypertensive agents but still have a role in some special agents but still have a role in some special situations ex. Pregnancy, resistant HT.situations ex. Pregnancy, resistant HT.

Considered cheap drugs.Considered cheap drugs.

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Drugs used in treatment of HT in pregnancyDrugs used in treatment of HT in pregnancy

Hydralazine.Hydralazine. Methyldopa. Methyldopa. Labetalol.Labetalol.

quiz. quiz. what is the group of each drug?what is the group of each drug?

adverse effects? adverse effects?

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The choice between the drugs;The choice between the drugs;

Weighing side effects & cost and patient clinical Weighing side effects & cost and patient clinical situation ! Examples:situation ! Examples:

asthmatics have been reported to have asthmatics have been reported to have worsening symptoms when using beta blockers. worsening symptoms when using beta blockers.

sometimes the presence of other symptoms can sometimes the presence of other symptoms can warrant the use of one particular warrant the use of one particular antihypertensive (such as beta blockers in case antihypertensive (such as beta blockers in case of tremor and nervousness.of tremor and nervousness.