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ANTI HYPERTENSIVE DRUGS
- 2. The Heart 2
- 3. Hypertension Systolic Blood Pressure (SBP( Diastolic Blood Pressure (DBP( <140mmHg <90mmHg **************************************************** Hypertension – The Silent Killer Hypertension, also known as high blood pressure, is defined as systolic blood pressure of 140 mmHg or higher and/or diastolic blood pressure of 90 mmHg or higher 3
- 4. Types of Hypertension Essential Secondary A disorder of unknown origin affecting the Blood Pressure regulating mechanisms Secondary to other disease processes Environmental Factors Stress Na+ Intake Obesity Smoking 4 ****************************************************
- 5. Normal Blood Pressure Regulation Hydraulic equation: Blood Pressure = Cardiac output (CO) X Resistance to passage of blood through precapillary arterioles (PVR) Physiologically CO and PVR is maintained minute to minute by – arterioles (1) postcapillary venules (2) and Heart (3) Kidney is the fourth site – volume of intravascular fluid Baroreflex, humoral mechanism and renin- angiotensin- aldosterone system regulates the above 4 sites Local agents like Nitric oxide In hypertensives – Baroreflex and renal blood- volume control system – set at higher level All antihypertensives act via interfering with normal mechanisms 5
- 6. Baroreceptor reflex arc Postural baroreflex: 6
- 7. The Renal response Long-term blood pressure control – by controlling blood volume Reduction in renal pressure - intrarenal redistribution of pressure and increased absorption of salt and water Decreased pressure in renal arterioles and sympathetic activity – renin production – angiotensin II production Angiotensin II: Causes direct constriction of renal arterioles Stimulation of aldosterone synthesis – sodium absorption and increase in intravascular blood volume 7
- 8. 8
- 9. Classification of Drugs 9 Ace Inhibitors Captopril, enalapril, lisinopril, perindopril, ramipril. Angiotensin antagonists Losartan, irbesartan, candesartan Calcium channel blockers Verapamil, diltiazam, nifedipine, felodipine, amlodipine, lacidipine Diuretics Thiazide=hydrochlorothiazide, chlorthalidone. indapamide High ceiling = furosemide K+ sparing = spironolactone.amiloride,
- 10. 10 ß - Adrenergic blockers Propranolol, metaprolol, atenolol. α+ß Adrenergic blockers Labetalol, carvedilol. sodium α - Adrenergic blockers prazosin., terazosin, phentolamine Central Sympatholytic Clonidine, methyldopa Vasodilators Hydralazine, minoxidil Renin inhibitors Aliskiren 5
- 11. 1. ACE Inhibitors Reni n Angiotensinoge n Angiotensin I Angiotensin II Binds to ZGand cell surface receptor Angiotensin III Aldosterone Production (Adrena cort ex) Angiotensin Converting Enzym What is Renin - Angiotensin? Physiology Renal Arterial Pressur e [Na*] in Renal Tubular Fluid Renal Sympathetic Nerve Activity Na+ & Water Retention Vasocontrictio n Rise in BP Increased Blood Volume Kidne y
- 12. ACE Inhibitors 12 ▪ Captopri l ▪ lisinopri l ▪ enalapril ▪ ramipril ▪ fosinopr il Angiotensin Converting Enzyme inhibito
- 13. Mechanism of action 13 Angiotensin Converting Enzyme inhibitors This group of drugs inhibit the enzyme kininase II or ACE. So these drugs decreases the activity of RAAS and also potentiate the vasodilatory action of bradykinin.
- 14. Adverse effects 14 ▪ Cough – persistent brassy cough in 20% cases – inhibition of bradykinin and substanceP breakdown in lungs ▪ Hyperkalemia in renal failure patients with K+ sparing diuretics, NSAID and beta blockers (routine check of K+ level) ▪ Hypotension (in hypovolemic states) – sharp fall may occur – 1st dose ▪ Acute renal failure- CHF and bilateral renal artery stenosis ▪ Angioedema - swelling of lips, mouth, nose etc. ▪ Rashes, urticaria etc
- 15. Adverse effects 15 hypoplasia of organs, growth retardation ▪ Foetopathic - etc ▪ Neutropenia ▪ Contraindications - Pregnancy, bilateral renal artery stenosis, hypersensitivity and hyperkalaemia
- 16. 16 • All are prodrugs except captopril & lisinopril • All are well absorbed orally • Food reduces absorption of captopril • DOA of captopril is 8-12 hrs rest others > 24 hrs • All are excreted through the kidneys
- 17. The End 17
Editor's Notes
- Baroreflexes are responsible for minute to minute regulation of BP. Central sympathetic neurones in vasomotor area are tonically active. When there is stretch in the vessel wall brought about by rise in pressure, baroreceptor stimulation occurs and inhibits sympathetic discharge. On the other hand reduction in stretch, increases baroreceptor activity. Therefore, there will be increase in PVR (constriction of arterioles), and increase in CO (increase in venous return due to constriction of capacitance venules and direct stimulation of heart – thereby restoring normal blood pressure. Acts in vasodilators and shock.