1 ANTIHYPERTENSIVE DRUGS

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3 Definition Elevation of arterial blood pressure above 140/90 mm Hg. Can be caused by: - idiopathic process (primary or essential hypertension ) an underlying disease process (secondary hypertension) Renal artery stenosis Hyperaldosteronism pheochromocytoma

4 Stages of Hypertension Stage Diastolic Range (mm Hg) Systolic Range (mm Hg) High Normal Stage Stage Stage 3> 109>179

5 Treatment Rationale Long-term goal of antihypertensive therapy: Reduce mortality due to hypertension-induced disease  Stroke  Congestive heart failure  Coronary artery disease  Nephropathy  Peripheral artery disease  Retinopathy

6 Ways of Lowering Blood Pressure Reduce cardiac output (ß- blockers, Ca 2+ channel blockers) Reduce cardiac output (ß- blockers, Ca 2+ channel blockers) Reduce plasma volume (diuretics) Reduce plasma volume (diuretics) Reduce peripheral vascular resistance (vasodilators) Reduce peripheral vascular resistance (vasodilators) MAP = CO X TPR

7 ANTI-HYPERTENSIVE DRUG CLASSES Diuretics Diuretics Beta blockers Beta blockers Vasodilators Vasodilators Calcium Channel Blockers Calcium Channel Blockers Angiotensin Converting Enzyme (ACE) Inhibitor Angiotensin Converting Enzyme (ACE) Inhibitor Alpha blockers Alpha blockers

8 Beta Blockers Atenolol Atenolol Propranolol Propranolol Metoprolol Metoprolol Labetalol Labetalol Timolol Timolol Nadolol Nadolol

9 Types of ß-blockers: Non selective Non selective Prototype: Propranolol (others: nadolol, timolol, pindolol, labetolol) Cardioselective Cardioselective Prototype: Metoprolol (others: atenolol, esmolol, betaxolol) Non selective and cardioselective ß-blockers are EQUALLY effective in reducing blood pressure Non selective and cardioselective ß-blockers are EQUALLY effective in reducing blood pressure

10 BETA - BLOCKERS ACTIONS : ACTIONS : DECREASES DECREASES  CARDIAC OUTPUT  BLOOD PRESSURE  SYMPATHETIC OUTFLOW  RENIN RELEASE  ALDOSTERONE RELEASE  PERIPHERAL RESISTANCE

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12 THERAPEUTIC USES For HTN For HTN HTN+ other diseases HTN+ other diseases –SVT –PREVIOUS MI –ANGINA –GLAUCOMA

13 SIDE EFFECTS CNS: fatigue, lethargy, insomnia, hallucinations CNS: fatigue, lethargy, insomnia, hallucinations Drug induced sexual dysfunction Drug induced sexual dysfunction Lipid profile : decrease HDL, Lipid profile : decrease HDL,

14 Contraindications Asthma Asthma (Beta 1 specific drugs can be used ) (Beta 1 specific drugs can be used ) PERIPHERAL VASCULAR DISORDERS PERIPHERAL VASCULAR DISORDERS Heart blocks Heart blocks CHF CHF

15 DIURETICS THIAZIDE DIURETICS HYDROCHLORTHIAZIDE HYDROCHLORTHIAZIDE CHLOROTHIAZIDE CHLOROTHIAZIDE CHLORTHALIDONE CHLORTHALIDONE INDAPAMIDE INDAPAMIDE METOLAZONE METOLAZONE LOOP DIURETICS FUROSEMIDE TORSEMIDE BUMETANIDE ETHACRYNIC ACID

16 ACTIONS MAINLY ACT BY MAINLY ACT BY Increasing the Na & water excretion, Increasing the Na & water excretion, Lower CO Lower CO Decrease extracellular volume Decrease extracellular volume Decrease renal blood flow Decrease renal blood flow Decrease B.P. Decrease B.P.

17 USES: HTN HTN CONGESTIVE CARDIAC FAILURE CONGESTIVE CARDIAC FAILURE

18 THIAZIDE SE : ( THIAZIDE ) SE : ( THIAZIDE ) HYPOKALEMIA arrhythmias HYPOKALEMIA arrhythmias HYPERURICEMIA precipitate gout HYPERURICEMIA precipitate gout HYPERGLYCEMIA impair glucose tolerance and increase insulin resistance. HYPERGLYCEMIA impair glucose tolerance and increase insulin resistance. NOT USED IN HYPERTENSIVE DIABETICS. NOT USED IN HYPERTENSIVE DIABETICS.

19 DIURETICS K SPARING DIURETICS AMILORIDE AMILORIDE SPIRONOLACTONE SPIRONOLACTONE TRIAMTERENE TRIAMTERENE They may be useful in combination with other diuretics to prevent hypokalaemia. They may be useful in combination with other diuretics to prevent hypokalaemia. Spironolactone is a specific aldosterone antagonist, with a particular role in primary hyperaldosteronism or Conn’s syndrome. Spironolactone is a specific aldosterone antagonist, with a particular role in primary hyperaldosteronism or Conn’s syndrome.

20 No risk of hypokalemia No risk of hypokalemia With spironolactone With spironolactonespironolactone breast enlargement in men (gynecomastia) and menstrual irregularities in women breast enlargement in men (gynecomastia) and menstrual irregularities in women

21 OTHER SYMPATHOLYTICS Alpha 1 blockers Prazosin Prazosin Terazosin Terazosin Doxazosin Doxazosin Central alpha 2 agonists Clonidine Guan Benz Guanfacine Alpha methyl dopa

22 Clonidine Alpha Methyldopa Does not decrease GFR, RBF Does not decrease GFR, RBF Use : HTN + renal disease Use : HTN + renal disease Side effect ; sedation, sodium retention dry mouth Side effect ; sedation, sodium retention dry mouth **Rebound hypertension** **Rebound hypertension**

23 Alpha 1 blockers - side effects Fainting (syncope) with the first dose, palpitations, Fainting (syncope) with the first dose, palpitations, dizziness, low blood pressure when the person stands (orthostatic hypotension), and fluid retention (edema) dizziness, low blood pressure when the person stands (orthostatic hypotension), and fluid retention (edema)

24 ACE - INHIBITORS DECREASES ANGIOTENSIN II DECREASES ANGIOTENSIN II DECREASES INACTIVATION OF BRADYKININ. DECREASES INACTIVATION OF BRADYKININ. Final effect : VASODILATION Final effect : VASODILATION Fall in B.P. Fall in B.P.

25 ACE INHIBITORS ENALAPRIL ENALAPRIL CAPTOPRIL CAPTOPRIL LISINOPRIL LISINOPRIL QUINAPRIL QUINAPRIL FOSINOPRIL FOSINOPRIL BENAZEPRIL BENAZEPRIL MOEXIPRIL MOEXIPRIL

26 USES HTN HTN CHF CHF POST MI POST MI Considered best drugs for HTN with DM. Considered best drugs for HTN with DM.

27 MC SIDE EFFECTS DRY COUGH due to decrease bradykinin metabolism DRY COUGH due to decrease bradykinin metabolism ALLERGY LIKE SYMPTOMS rash, angioedema ALLERGY LIKE SYMPTOMS rash, angioedema RHINORRHOEA RHINORRHOEA HYPERKALEMIA HYPERKALEMIA low blood pressure low blood pressure

28 CONTRAINDICATIONS PREGNANCY PREGNANCY RENOVASCULAR STENOSIS RENOVASCULAR STENOSIS  MAY PRECIPITATE ARF

29 ANGIOTENSIN II RECEPTOR ANTAGONISTS LOSARTAN LOSARTAN Valsartan Valsartan Candesartan Candesartan Eprosartan Eprosartan Irbesartan Irbesartan Telmisartan Telmisartan

30 LESS SEVERE SIDE EFFECTS LESS SEVERE SIDE EFFECTS Bradykinin is not produced Bradykinin is not produced Angioedema rare Angioedema rare CI ::::: PREGNANCY CI ::::: PREGNANCY

31 CALCIUM CHANNEL BLOCKERS VERAPAMIL VERAPAMIL DILTIAZEM DILTIAZEM NIFEDIPINE NIFEDIPINE AMLODIPINE AMLODIPINE FELODIPINE FELODIPINE NICARDIPINE NICARDIPINE NISOLDIPINE NISOLDIPINE

32 ACTION BLOCKS CALCIUM CHANNELS IN HEART AND CORONARY AND PERIPHERAL VESSELS BLOCKS CALCIUM CHANNELS IN HEART AND CORONARY AND PERIPHERAL VESSELS DECREASES CYTOPLASMIC CALCIUM LEVELS DECREASES CYTOPLASMIC CALCIUM LEVELS SMOOTH MUSCLE RELAXES SMOOTH MUSCLE RELAXES DILATES ARTERIOLES DILATES ARTERIOLES

33 NIFIDIPINE, - MORE EFFECT ON PERIPHERAL VESSELS NIFIDIPINE, - MORE EFFECT ON PERIPHERAL VESSELS MINIMAL EFFECT ON HEART CONDUCTION AND HR MINIMAL EFFECT ON HEART CONDUCTION AND HR

34 VERAPAMIL – MORE EFFECT ON HEART VERAPAMIL – MORE EFFECT ON HEART DECREASES CONDUCTION, HR,OXYGEN DEMAND DECREASES CONDUCTION, HR,OXYGEN DEMAND MORE - VE IONOTROPISM MORE - VE IONOTROPISM

35 USES HTN HTN ANGINA ANGINA PERIPHERAL VASCULAR DISEASE PERIPHERAL VASCULAR DISEASE ARRHYTHMIA ARRHYTHMIA CAN BE USED IN PT’S WITH HTN ALONG WITH ASTHMA OR DM CAN BE USED IN PT’S WITH HTN ALONG WITH ASTHMA OR DM

36 SIDE EFFECTS DIZZINESS DIZZINESS HEADACHE HEADACHE REFLEX TACHYCARDIA REFLEX TACHYCARDIA CARDIAC DEPRESSION CARDIAC DEPRESSION FLUSHING FLUSHING

37 VASODILATORS HYDRALAZINE HYDRALAZINE MINOXIDIL MINOXIDIL

38 ACTIONS Cardiovascular Effects: Greater effect on diastolic blood pressure Greater effect on diastolic blood pressure Reduce systemic vascular resistance Reduce systemic vascular resistance

39 HYDRALAZINE USESHTN,CHF. SE: whose main side effect is a lupus-like syndrome SLE NAUSEA VOMITING HEADACHE FLUID RETENTION ARRHYTHMIA ANGINA

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41 MINOXIDIL SE: SE: SODIUM AND WATER RETENTION SODIUM AND WATER RETENTION VOLUME OVERLOAD VOLUME OVERLOAD LEADING TO EDEMA & CHF LEADING TO EDEMA & CHF USED FOR TREATING REFRACTORY HTN USED FOR TREATING REFRACTORY HTN HYPERTRICHOSIS HYPERTRICHOSIS  For baldness

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44 SODIUM NITROPRUSSIDE Direct-acting, nonselective peripheral vasodilator Direct-acting, nonselective peripheral vasodilator Relaxation of arterial and venous vascular smooth muscle Relaxation of arterial and venous vascular smooth muscle

45 EFFECTS CVS BOTH ARTERIES AND VEINS ARE AFFECTED (dilated) BOTH ARTERIES AND VEINS ARE AFFECTED (dilated) FALL IN B.P. FALL IN B.P. Reduces preload and afterload Reduces preload and afterload

46 ACTIONS NITROPRUSSIDE BINDS WITH OXY Hb OXY Hb FORMING METH Hb FORMING METH Hb AND RELEASES NO AND RELEASES NO ALSO CYANIDE IONS ALSO CYANIDE IONS

47 USES IV ROUTE IV ROUTE DURING SURGERIES DURING SURGERIES ***HTN EMERGENCIES*** ***HTN EMERGENCIES*** TOXICITY – CYANIDE TOXICITY TOXICITY – CYANIDE TOXICITY R X SODIUM THIOSULFATE R X SODIUM THIOSULFATE

48 DIAZOXIDE DIRECT ACTING ARTERIOLAR VASODILATOR. DIRECT ACTING ARTERIOLAR VASODILATOR. IV ROUTE IV ROUTE ***HTN EMERGENCIES*** ***HTN EMERGENCIES*** SE; EXCESSIVE HYPOTENSION SE; EXCESSIVE HYPOTENSION