B) Drug Therapy (Antihypertensives) ACEi B.B CCB D iuretics. Centrally acting agents: alphametyldopa, HTN + pregnancy

DIURETICS Mechanisms of Diuretics as an Antihypertensive Direct vasodilator effect. ↓ vascular receptor sensitivity to Vaso active substance ↑ Increase synthesize of the vasodilator PGs. ↓ cardiac output due to ↓ blood volume by the diuretic action. Indications of Diuretics in Hypertension Initial therapy in most hypertensive patients. Hypertensive crises. Chronic renal failure

BETA BLOCKERS Indications of beta-blockers in hypertension: HTN+ stable angina HTN+ arrhythmias. HTN+ Hyperrenenimic HTN+ thyrotoxicosis -- MOA of B.B as anithypertention ↓force of contraction, ↓ H.R, ↓ cardiac output ↓ Renin release

Classification: C.C.B.with cardiac effects e.g. verapamil and diltiazem.> - ve inotropic effect can’t use them in H.failure C.C.B.with vascular effects e.g. nifedipine, isradipine. C.C.B.with tissue protection e.g. flunarizine, nifedipine. Calcium channel blockers

Pharmacological Effects: Smooth muscle: relaxation Cardiac muscle: Verapamil and diltiazem reduce cardiac contractility Other: Verapamil inhibits insulin release.

Therapeutic Indications* IMPORTANT A) C.C.B.with cardiac effects are used in treatment of: 1-Ischemic heart disease: all types of angina and myocardial infarction. Mechanisms of action in Ischemic heart diseases ↓arterial blood pressure, ↓ force of contraction. Coronary V.D 2-Cardiac arrhythmias 3-Hypertrophic obstructive cardiomyopathy: only verapamil and diltiazem. 4-Arterial hypertension:

C.C.B.with vascular effects 1.Arterial hypertension: 2.Cerebral vasospasm 3.Peripheral vascular disease. 4.Chronic renal failure

Adverse Effects Verapamil or diltiazem aggravate congestive heart failure. Verapamil or diltiazem can cause A.V. block in certain situation. Verapamil can cause hepatotoxicity with prologed use. Verapamil decrease insulin realease. Nifedipine can cause hypotension, flushing, nasal congestion, tinitus. Ankle edema (with nifedipine or verapamil).

Contraindications and precautions Verapamil should be used with great caution in the presence of heart failure, unstable AV block, sick sinus syndrome, low blood pressure states. Nifedipine is contraindicated in idiopathic hypertrophic subaortic stenosis, and unstable angina.

Inhibitors of Renin Angiotensin System: Inhibition of renin release: by beta-blockers, clonidine, alpha methyl dopa Rennin activity inhibitors e.g. enalakrine Angiotensin converting enzyme inhibitors (ACEIs): ACEIs with Sulph-hydryl containing ACEIs: Captopril. ACEIs without sulph-hydryl group: Enalapril ACEIs inhibitors which contain phosphinate group e.g. Fosinopril. Angiotensin II receptor blockers : Losartan, Valsartan.

Mechanism of Action of ACEIs 1. Inhibition of ACE (Angiotensin converting enzyme ) 2. Prevent inactivation of kinins= marked vasodilator.

Clinical Uses Hypertension. Heart failure.

Adverse Effects First dose hypotension. Cough and bronchospasm. Angiedema. Neutropenia. Skin rashes. Hyperkalaemia. Temporary loss of taste. Headache, dizziness and fatigue.

Contraindications Hypotension: Hyperkalaemia. Severe anaemia. Bilateral renal artery stenosis or stenosis in a solitary kidney. Pregnancy and breast-feeding

Precautions during Use of ACEIs Initial dose should be low. Diuretic use with caution. Measurement of blood urea and creatinine Electrolyte assay specially potassium.

ANGIOTENSIN II RECEPTOR BLOCKERS Losartan, valsartan,candesartan Like ACEi but less side effect They have no effect on bradykinin metabolism. Don’t give to pregnant female

VASODILATORS Classifications Arteriolar vasodilators: e.g. nifedipine, Venodilators: e.g. nitrates. Mixed arterio and venodilators: sodium nitroprusside, ACEIs

MINOXIDIL Adverse effects Hypertrichosis: so should not used in female. But used locally in baldness

SODIUM NITROPRUSSIDE Arteriolar and venodilator effect Sever cases of hypertension Can’t used in hepatic pt

ALPHA METHYL DOPA It stimulates central alph 2 receptors. It in hibits renin release. It can be used in cases of hypersion with pregnancy.

CONCURRENT ALPHA AND BETA ADRENOCEPTOR BLOCKERS LABETALOL It blocks both alpha and beta-receptors like carvidalol But carvidalol It blocks  and  receptors. It has dircet V.D. effect. It has anti oxidant effect. It can be used in treatment of heart failure.

HYPERTENSIVE EMERGENCIES hospitalised. Reduction of blood pressure should be in hours and not in minutes. Sublingual nifedipine Parenteral therapy: Diuretics Reserpine(adrenergic neuron blocker) 1-2 mg I.M Sodium nitroprusside infusion Hydralazine Beta blocker Methyl dopa Nifedipine Nitroglycerin