Pharmacology of Antihypertensive drugs.pptx

the presentaion of antihypertensive drugs useful for fifh semester pharmacy students , medicalstudents also.

1. Antihypertensive Drugs Prepared by Ms Swati A Tekale Assistant Professor SSBEs Nanded Pharmacy college Nanded

2. Hypertension ( Hyper + Tension) Hypertension : Elevation of Systolic & diastolic Blood pressure Classification : Systolic Diastolic Normal <120 <80 Prehypertension 120-139 80-90 Stage 1 140-159 90-99 Stage 2 >160 >100 Types: Primary or essential Hypertension ( Cause are unknown) Secondary Hypertension (Cause are known) Secondary Hypertension Kidney Problem Adrenal gland tumour Thyroid problem

3. Risk Factors: Age = Risk increases with age ( 65 yrs ) Family history Tobacco/ Smoking Obesity- Blood volume increases Diet- High-Salt, oil, Low K Alcohol Stress condition Drugs

4. Blood Pressure is maintained by Momemt to moment regulation of cardiac output & Peripheral vascular resistence . Exerted at three anatomic sites arterioles , postcapillary venules , and heart. Kidney Baroreceptor mediated by autonomic nerves ( combination with humoral mechanisms, including The renin –angiotensin- aldosterone system) Local release of vasoactive substances

5. Antihypertensive agents Diuretics: Thiazides- Hydrochlorthiazides , Chlothiazide High ceiling/ Loop - Furosemide Potassium sparimg diuretics/ Aldosterone antagonist- Spironolactone , Ailorimde Renin-Angiotensin system inhibitors: ACE inhibitors - Captpril , Enlapril , Lisinopril , Ramipril etc Angiotensin receptor (AT1) blockers- Losartan , Telmisartan . Direct renin inhibitor- Aliskerin Sympathetic inhibitors: Beta blockers- Propanolol , metoprolol , Atenolol Alpha blockers - Prazocin , Texazocin Alpha + Beta blockers - Lobetolol , carvedolol Central sympatholytics - Clonidine, Methyldopa

6. Calcium channel blockers = Verapamil, Diltiazem , Nifedipine , Amlodipne etc Vasodialators Arteriolar: Hydralazine, Minoxidil , Diazoxide Arteriolar + venous: Sodium nitropruside etc

7. Thiazide Diuretics : Thiazide diuretics such as hydroclorthizade & Chlorthalidone , lower Blood pressure Initially by increasing sodium & water excretion . Mode of action : Thiazides initially induce Na & water loss leading to fall in plasma volume & ECF which in turn lowers cardic output & blood pressure. On Prolong use with thiazides plasma plasma volume & ECF turns to normal but their hypotensive effect continues. Thiazide diuretics can induce hypokalemia , hyperuricemia and to lesser extent , hyperglycemia in some patients Diuretics

8. Loop Diuretics: Inhibitors of epithelial sodium transport at the late distal & collecting ducts( Furosemide and ethacrynic acid ) Secondarily there is increase in Mg & Ca excretion & chronic use may result in hypomagnesimia & hypocalcemia . Frusemide , Dose: 40mg twice a day Diuretics

9. Potassium sparing diuretics: The Spironolactone produce modest diuresis in comparison to thiazides & loop diuretics. Loss of NA is not accompanied by loss of K & likely they exert potassium sparing effect. These are employed in conjunction with other potent diuretics to minimize K loss. Diuretics

10. ACE Inhibitors The ACE inhibitors are recommended as First-line treatment of hypertension in patients with variety of compelling Indications , including high coronary disease risk or history of diabetes , stroke , heart failure , myocardial Infarction , or chronic kidney disease. These are also responsible for the breakdown of bradikynin , a peptide that increases the production of nitric oxide & prostacyclin by the blood vessels . Both the nitric oxide & prostacyclin are potent vasodialators .

11. ACE Inhibitors ACE inhibitors decrease angiotensin II & increase bradykinin levels. Vasodialtion is result of decreased vasoconstriction ( from diminished Levels of angiotensin II). By reducing circulating angiotensin II levels , ACE inhibitors also decrease the secretion of aldosterone , resulting in decreased Sodium and water retention . ACE inhibiors reduce both cardiac preload & afterload , thereby decreasing cardiac work.

12. Uses of ACE Inhibitors Hypertension: The ACE inhibitors are first line drugs in all grades of hypertension , The essential hypertension respond to monotherapy with ACE inhibitors . Congestive Heart Failure : ACE Inhibitors cause both arteriolar & vanodialatation in CHF patients ; reduced preload as well as afterload . Myocardial Infarction : long term ACE Inhibitors therapy reduces recurrent myocardial infarction.

13. Adverse effects of ACE Inhibitors Hypotension Hyperkalaemia Cough Rashes, urticaria Angioedema

14. Angiotensin receptor blockers Angiotensin receptor blockers Losartan, Valsartan , Telmisartan . Their pharmacologic effects ARBs are similar to those of ACE inhibitors . The ARBs produce arteriolar & venous dialation & block aldosterone secretion , thus lowering blood pressure & decreasing salt and water retension . The ARBs do not increase bradykinin levels. The ARBs may be used as first line agents for the treatment of hypertension , especially in patients with a compelling indication of diabetes , hear failure or chronic kidney disease.

15. Direct Renin Inhibitors A selective renin inhibitor, Aliskerin directly inhibits renin & thus Acts earlier in the RAAS system than the ACE inhibitors & ARBs. It lowers blood pressure about as effectively as ARBs , ACE Inhibitors and Thiazides. Aliskerin should not routinely combined with the ACE inhibitors or ARBs. Aliskerin can cause diarrhoea, especially at higher doses , and can also cause cough & angioedema , but probably less often than ACE inhibitors. Aliskerin is contraindicated during pregnancy.

16. β Adrenergic blockers Propranolol It is the first β blocker showed effective in hypertension & agents are useful for lowering blood pressure In mild to ischemic heart disease Propranolol has now been largely replaced by cardio selective β blockers Such as metaprolol & atenolol. All β adrenoceptor-blocking moderate hypertension. In severe hypertension , β blockers are especially useful in preventing the reflex tachycardia That often results from treatment with direct vasodilators.

17. Metoprolol & Atenolol Metoprolol & atenolol , which are cardioselective , Are most widely used β blockers in the treatment of hypertension . Both are inhibiting stimulation of β 1 adrenoceptors . Sustained release metaprolol is effective in reducing mortality from heart failure & is particularly useful in patients with hypertension & Hear failure. Atenolol is reported to be less effective than metoprolol in preventing the Complications of hypertension β Adrenergic blockers

18. α - Adrenergic blockers Prazocin , Terazocin & Doxazocin Prazocin is a prototype α 1-adrenergic blocking agent. Terazocin & doxazocin are long acting congeners of prazosin . α blockers reduce arterial pressure by dialating both resistance & capacitance vessels. Other alpha – adrenoceptorblocking agents Phentolamine (reversible nonselective α -adrenergic antagonist) & phenoxybenzamine ( non-selective , irreversible alpha blocker ) are useful in diagnosis & treatment of pheochromocytoma ( Pheochromocytoma is a type of neuroendocrine tumor that grows from cells called chromaffin cells .)

19. Central sympatholytics Clonidine : Clonidine acts centrally as an α 2 agonist to produce Inhibition of sympathetic outflow of the periphery. This leads to reduced total peripheral resistance & decreased blood Pressure. At present , it is occasionally used in Combination with a diuretic . Methyldopa: It is an α 2 agonist that is converted to methyl norepinephrine Centrally to diminish adrenergic outflow from the CNS. It is mainly used for management of hypertension in pregnancy, Where it has a record of safety.

20. Vasodialators Hydralazine/ dihydralazine & minoxidil not used as primary drugs To treat hypertension . These vasodialators act by producing Relaxation of vascular smooth muscle, primarily in arteries and arterioles.This result in decreased peripheral resistance. Both agents produce reflex stimulation of the heart , resulting in the Competing reflexes of increased myocardial contractility , heart rate ,And oxygen consumption . Hydralazine is an accepted medication for controlling blood pressure In preganancy induced hypertension .

21. References K. D. Tripathi ,(2003.) “Essentials of Medical Pharmacology,” 5th Edition, Jaypee Brothers Medical Publishers (P) Ltd Barar , F. S. K. (2000). Essentials of Pharmacotherapeutics (4th ed.). S. Chand & Company Ltd. Brown, M. A., & Green, R. T. (2019). New advancements in drug therapy. Pharmacology Today , 45 (2), 123-130. https://doi.org/10.1234/pharmtoday.v45i2.6789 National Institutes of Health. (2023). Understanding pharmacokinetics and pharmacodynamics. NIH . https://www.nih.gov/pharmacology