ANTIHYPERTENSIVE DRUGS

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

Stages of Hypertension Diastolic Range (mm Hg) Systolic Range (mm Hg) High Normal 85-89 130-139 Stage 1 90-99 140-159 Stage 2 100-109 160-179 Stage 3 > 109 >179

Treatment Rationale Stroke Congestive heart failure 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

Ways of Lowering Blood Pressure MAP = CO X TPR Reduce cardiac output (ß-blockers, Ca2+ channel blockers) Reduce plasma volume (diuretics) Reduce peripheral vascular resistance (vasodilators)

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

Beta Blockers Atenolol Propranolol Metoprolol Labetalol Timolol Nadolol

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

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

THERAPEUTIC USES SUPRAVENTRICULAR TACHYCARDIA PREVIOUS MI ANGINA For HTN( first line agents chosen to treat patients with mild to moderate HTN) HTN+ other diseases SUPRAVENTRICULAR TACHYCARDIA PREVIOUS MI ANGINA GLAUCOMA

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

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

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

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

USES: HTN CONGESTIVE CARDIAC FAILURE

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

DIURETICS K SPARING DIURETICS AMILORIDE SPIRONOLACTONE TRIAMTERENE 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.

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

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

Clonidine Alpha Methyldopa Does not decrease GLOMERULAR FILTRATION RATE AND RENAL BLOOD FLOW RATE Use : HTN + renal disease These drugs decrease total peripheral resistance without changing CO. This drugs has no direct effect on the kidney and can be used in patients with renal disease Side effect ; sedation, sodium retention dry mouth **Rebound hypertension**

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

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

ACE INHIBITORS ENALAPRIL CAPTOPRIL LISINOPRIL QUINAPRIL FOSINOPRIL BENAZEPRIL MOEXIPRIL

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

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

CONTRAINDICATIONS PREGNANCY RENOVASCULAR STENOSIS MAY PRECIPITATE ACUTE RENAL FAILURE

ANGIOTENSIN II RECEPTOR ANTAGONISTS LOSARTAN Valsartan Candesartan Eprosartan Irbesartan Telmisartan

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

CALCIUM CHANNEL BLOCKERS VERAPAMIL DILTIAZEM NIFEDIPINE AMLODIPINE FELODIPINE NICARDIPINE NISOLDIPINE

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

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

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

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

SIDE EFFECTS DIZZINESS HEADACHE REFLEX TACHYCARDIA CARDIAC DEPRESSION FLUSHING

VASODILATORS HYDRALAZINE MINOXIDIL

ACTIONS Cardiovascular Effects: Greater effect on diastolic blood pressure Reduce systemic vascular resistance Increased: (baroreceptor reflex-mediated; some direct cardiac effect also likely) heart rate stroke volume cardiac output Limited orthostatic hypotension --secondary to greater effect on arterioles than veins

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

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

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

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

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

USES ***HTN EMERGENCIES*** IV ROUTE DURING SURGERIES TOXICITY – CYANIDE TOXICITY RX SODIUM THIOSULFATE

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