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HYPERTENSION

HYPERTENSION. CREATED BY Prof. Azza El- Medany. Head Lines. Etiology Risk factors Mechanism Complications Treatment. Response mediated by the renin-angiotensin & sympatheic system on blood pressure. Antihypertensive Agents. Diuretics

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HYPERTENSION

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  1. HYPERTENSION CREATEDBY Prof. Azza El-Medany

  2. Head Lines • Etiology • Risk factors • Mechanism • Complications • Treatment

  3. Response mediated by the renin-angiotensin & sympatheic system on blood pressure

  4. Antihypertensive Agents • Diuretics • Drugs acting on sympathetic system • Direct vasodilators • Drugs acting on renin-angiotensin aldosterone system • Calcium channel blockers

  5. DIURETICS • Initially they increase sodium & water excretion this cause : • Reduction blood volume & C.O. • Late : Reduce peripheral resistance • Indapamide has a direct vasodilating effect

  6. Clinical uses • Are effective alone for mild or moderate essential hypertension ( Thiazide ). • In severe hypertension they are given in combination with other antihypertensive agents. • Loop diuretics are used in severe hypertension even in patients with impaired renal function. • Potassium-sparing diuretics in patients taking digitalis.

  7. Centrally acting sympathoplegic • Clonidine • Stimulate central α2 –adrenoceptors • DecreasingPVR • Useful in hypertension complicated by renal disease • Sedation & drying of the nasal mucosa • Rebound hypertension

  8. Continue α-methyl dopa α2-agonist Valuable in treating hypertensive patients with renal insufficiency In pregnant women

  9. Adrenoceptor –Blocking Agents • β adrenoceptors are very useful in mild to moderate hypertension. • In severe cases used in combination with other agents. • They lower blood pressure: Primarily by decreasing cardiac output. Inhibiting the release of renin from kidney. • E.g. Propranolol , atenolol , metoprolol

  10. Selective α1- adrenoceptor blockers • The selectivity for α1-receptors produce less reflex tachycardia than non selective. • More effective when given in combination with β-blockers or diuretics. • E.g.Prazocin

  11. VASODILATORS

  12. Compensatory Response to Vasodilators

  13. CALCIUM CHANNEL BLOCKERS

  14. Inhibit calcium influx into arterial smooth muscles & cardiac muscles. • Dihydropyridine group (amlodipine, nifedipine) are more selective as arteriodilators ( decreasing afterload) • Verapamil &Diltiazem aremore selective as cardiac depressant ( decreasing C.O) .

  15. Notic Increase the risk of myocardial infarction or mortality in patients receiving short-acting nifedipine for hypertension. It is recommended to use sustained-release calcium blockers or calcium blockers with long half- lives. Intravenous nicardipine or verapamil or diltiazem can be used.

  16. Inhibitors of renin angiotensin system • Angiotensin converting enzyme inhibitors (ACEI). • Inhibits ACE which lead to : • Inhibits the synthesis of angiotensin II. • Stimulate the action of Kallikrein-Kinin system.

  17. ACEI • Lower blood pressure by decreasing peripheral vascular resistance. • No significant change in C.O or heart rate. • (Unlike direct vasodilator , no reflex sympathetic activation , so they can be used safely in patients with ischemic heart disease).

  18. Sites of action of ACE inhibitors & Receptor blockers

  19. Pharmacokinetics • Captopril, enalapril, moxepril. • Absorbed from GIT after oral administration. • Food reduce their bioavailability. • All are pro-drugs, converted to the active agents by hydrolysis in the liver (Except Captopril). • Captopril is short acting(2-3times/daily)

  20. Phrmacokinetics • The others are long acting. • Enalaprilat is the active metabolite of enalapril is available only for intravenous use for hypertensive emergency. • All ACEI are distributed to all tissues except CNS. • ACEI are eliminated by the kidney except moexpril.

  21. Clinical uses • More effective in treatment of hypertension in conditions associated with high plasma renin activity ( young & white people ). • Safely used in patients with ischemic heart disease. • Are useful in treating patients with diabetic nephropathy • Treatment of heart failure.

  22. Adverse effects • Severe hypotension • Acute renal failure • Hyperkalemia • Dry cough, wheezing ,and angioedema • Captopril may cause loss of taste &in high doses may cause neutropenia , proteinuria, .

  23. Contraindications • During the second and third trimesters of pregnancy because of the risk of fetal hypotension ,anuria ,renal failure , fetal malformations and death. • Bilateral renal artery stenosis or stenosis of the artery of a solitary kidney.

  24. Drug interactions • With potassium-sparing diuretics • NSAIDs impair their hypotensive effects by blocking bradykinin-mediated vasodilatation.

  25. 2-Angiotensin receptor –blocking agents • Mechanism of action : • Block AT1 receptors. • Advantages over ACEI : • They have no effect on bradykinin system: No cough,wheezing or angioedema. • Complete inhibition of angiotensin action compared with ACEI

  26. Losartan • Orally effective • Has a potent active metabolite. • Long half-life , taken once daily. • Can not cross BBB

  27. Adverse effects • As ACEI exceptfor cough ,wheezing ,and angioedema. • Same contraindications as ACEI.

  28. Hypertensive Emergency Drugs • Sodium nitroprusside • Diazoxide • Labetalol( α & β blocker ) • Nicardipine

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