1 Anti Hypertensive Agents. Dr. Aisha AL-Ghamdi Associate professor Consultant internist

2  Antihypertensives are a class of drugs that are used in medicine and pharmacology to treat hypertension. drugsmedicine pharmacologyhypertensiondrugsmedicine pharmacologyhypertension  Evidence suggests that reduction of the blood pressure by 5-6 mmHg can decrease the risk of Stroke by 40%, Coronary heart disease by15-20% and reduces the likelihood of dementia, heart failure, and mortality from cardiovascular disease. blood pressuredementiaheart failuremortalitycardiovascular disease blood pressuredementiaheart failuremortalitycardiovascular disease

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

4 DIURETICS  help the kidneys eliminate excess salt and water from the body's tissues and blood.  Loop diuretics: bumetanide bumetanide bumetanide ethacrynic acid ethacrynic acid ethacrynic acid ethacrynic acid furosemide furosemide furosemide torsemide torsemide torsemide

5 CONT. Thiazide diuretics Thiazide diuretics  chlortalidone chlortalidone  epitizide epitizide  hydrochlorothiazide and chlorothiazide hydrochlorothiazidechlorothiazide hydrochlorothiazidechlorothiazide  bendroflumethiazide bendroflumethiazide

6 CONT. Thiazide-like diuretics: Thiazide-like diuretics:  indapamide indapamide  chlorthalidone chlorthalidone  metolazone metolazone Potassium-sparing diuretics: Potassium-sparing diuretics:  amiloride amiloride  triamterene triamterene  spironolactone spironolactone

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

8 CONT. The reason why thiazides-type diuretics are better than the others is because of The reason why thiazides-type diuretics are better than the others is because of 1. Their vasodilating properties. 2. The diuretic effect of thiazides may be apparent shortly after administration. 3. The full anti-hypertensive effect to develop.takes longer (weeks of treatment). {disadvantage !!}

9 Adverse effects of thiazides ; 1. Hypokalemia → arrhythmias 2. Hyperuricaemia → acute gout. 3. increase serum LDL- cholesterol and TG. 4. Impair glucose tolerance and increase insulin resistance. Reports of frank diabetes are rare. Although thiazides probably should be avoided as first-line drugs in patients with diabetes and hyperlipidaemia. 5. Rarer side effects include nausea, headache, rashes, photosensitivity and blood dyscrasias.

10 Adrenergic receptor antagonists  Beta blockers; (no longer 1st line therapy in many countries) (no longer 1st line therapy in many countries) atenololatenolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, timolol. metoprololnadololoxprenolol pindololpropranololtimolol atenololmetoprololnadololoxprenolol pindololpropranololtimolol  Alpha blockers; Doxazosin, phentolamine, indoramin, phenoxybenzamine, prazosin,terazosin, tolazoline. Doxazosin, phentolamine, indoramin, phenoxybenzamine, prazosin,terazosin, tolazoline.Doxazosinphentolamineindoramin phenoxybenzamineprazosinterazosin tolazolineDoxazosinphentolamineindoramin phenoxybenzamineprazosinterazosin tolazoline  Mixed Alpha + Beta blockers; bucindololbucindolol, carvedilol, labetalol. carvedilollabetalol bucindololcarvedilollabetalol

11 beta-receptor Types →ß 1 ß 2 ß 3 Types →ß 1 ß 2 ß 3  Vasodilation (b2)  Cardioacceleration (b1)  Intestinal relaxation (b2)  Uterus relaxation(b2)  Bronchodilation (b2)

12 Adverse effects of b-blockers;  slow the rate of conduction at the atrio- ventricular node.  Sinus bradycardia is common and is not a reason to stop beta-blockers unless the patient is symptomatic or the heart rate falls below 40 beats/minute.

13 contraindicated in;  Patients with 2 nd and 3 d degree heart block.  Asthmatics  rest ischaemia of the legs (Blockade of b receptors in the peripheral circulation → vasoconstriction)  Diabetics (theoretically, reduce the awareness of low blood glucose →mask hypoglycemic symptoms).

14 Adrenergic receptor agonist. Adrenergic receptor agonist. Alpha-2 agonists Alpha-2 agonists Revise (α-receptors sites, function) clonidine clonidine clonidine methyldopa methyldopa methyldopa

15 alpha-receptor Types → α 1 (A,B,D), α 2 (A,B,C) Types → α 1 (A,B,D), α 2 (A,B,C)  Vasoconstriction  iris dilation  intestinal relaxation  intestinal sphincter contraction  bladder sphincter contraction

16 Calcium 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; amlodipine amlodipine amlodipine felodipine felodipine felodipine isradipine isradipine isradipine lercanidipine »peripheral vasodilatation→ reflex tachycardia. lercanidipine »peripheral vasodilatation→ reflex tachycardia. lercanidipine nifedipine(Adalat®) nifedipine(Adalat®) nifedipine nimodipine nimodipine nimodipine nitrendipine nitrendipine nitrendipine  Non-dihydropyridines; diltiazem, verapamil. diltiazemverapamildiltiazemverapamil »peripheral vasodilatation+ ↓ HR. »peripheral vasodilatation+ ↓ HR.

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

18 ACE inhibitors  captopril captopril  enalapril enalapril  fosinopril fosinopril  lisinopril lisinopril  perindopril perindopril  quinapril quinapril  ramipril ramipril  trandopril trandopril  benzapril benzapril

19 Adverse effects of ACEI;  Cough commonest, more in females and older patients.  Angioedema more serious, but rare, which occurs in about 0.1 to 0.2 per cent of patients.  Dramatic deterioration in renal function can occur in patients with bilateral renal artery stenosis. Serum urea and creatinine should, therefore, be checked before and a few weeks after starting an ACE inhibitor.

20 Angiotensin II receptor antagonists  Angiotensin II receptor antagonists work by antagonizing the activation of angiotensin receptors. Angiotensin II receptor antagonistsantagonizingangiotensin receptors Angiotensin II receptor antagonistsantagonizingangiotensin receptors  candesartan candesartan  eprosartan eprosartan  irbesartan irbesartan  losartan losartan  olmesartan olmesartan  telmisartan telmisartan  valsartan valsartan

21 Adverse effects of Angiot.II R.A.  hyperkalaemia, renal impairment and hypotension. They are almost as well tolerated as placebo. Nevertheless, cases of angioedema have been reported with some of these agents.

22 Aldosterone antagonists Aldosterone antagonists  Eplerenone.  Spironolactone. Aldosterone antagonists are not recommended as first-line agents for blood pressure,but spironolactone and eplerenone are both used in the treatment of heart failure. Aldosterone antagonists are not recommended as first-line agents for blood pressure,but spironolactone and eplerenone are both used in the treatment of heart failure.Aldosteronespironolactone eplerenoneheart failureAldosteronespironolactone eplerenoneheart failure

23 Vasodilators Vasodilators Vasodilators act directly on arteries to relax their walls so blood can move more easily through them;used in Vasodilators act directly on arteries to relax their walls so blood can move more easily through them;used inVasodilators medical emergencies. medical emergencies.medical emergenciesmedical emergencies  sodium nitroprusside used in medical emergencies. medical emergenciesmedical emergencies  Hydralazine.

24 Centrally acting adrenergic drugs Centrally acting adrenergic drugs  Clonidine, Guanabenz, Methyldopa, Central alpha agonists lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow. Central alpha agonists, such as clonidine, are usually prescribed when all other anti- hypertensive medications have failed. For treating hypertension, these drugs are usually administered in combination with a diuretic. ClonidineGuanabenzMethyldopa ClonidineGuanabenzMethyldopa

25 CONT.  Adverse effects of this class of drugs include sedation, postural hypotension, drying of the nasal mucosa and rebound hypertension.  Some adrenergic neuron blockers are used for the most resistant forms of hypertension:  Guanethidine Guanethidine  Reserpine Reserpine

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

27 Drugs used in treatment of HT in pregnancy  Hydralazine.  Methyldopa.  Labetalol. quiz. what is the group of each drug? quiz. what is the group of each drug? adverse effects? adverse effects?

28 The choice between the drugs;  Weighing side effects & cost and patient clinical situation ! Examples: asthmatics have been reported to have worsening symptoms when using beta blockers. asthmatics have been reported to have worsening symptoms when using beta blockers.asthmaticsbeta blockersasthmaticsbeta blockers sometimes the presence of other symptoms can warrant the use of one particular antihypertensive (such as beta blockers in case of tremor and nervousness. sometimes the presence of other symptoms can warrant the use of one particular antihypertensive (such as beta blockers in case of tremor and nervousness.tremornervousnesstremornervousness