Head Lines Etiology Risk factors Mechanism Complications Treatment

Response mediated by the renin-angiotensin & sympatheic system on blood pressure

Antihypertensive Agents Diuretics Drugs acting on sympathetic system Direct vasodilators Drugs acting on renin-angiotensin aldosterone system Calcium channel blockers

DIURETICS Initially they increase sodium & water excretion this cause : Reduction blood volume & C.O. Late : Reduce peripheral resistance Indapamide has a direct vasodilating effect

Clinical uses Are effective alone for mild or moderate essential hypertension ( Thiazide ). In severe hypertension they are given in combination with other antihypertensive agents. Loop diuretics are used in severe hypertension even in patients with impaired renal function. Potassium-sparing diuretics in patients taking digitalis.

Centrally acting sympathoplegic Clonidine Stimulate central α 2 –adrenoceptors Decreasing PVR Useful in hypertension complicated by renal disease Sedation & drying of the nasal mucosa Rebound hypertension

Continue α-methyl dopa α 2 -agonist Valuable in treating hypertensive patients with renal insufficiency In pregnant women

Adrenoceptor –Blocking Agents β adrenoceptors are very useful in mild to moderate hypertension. In severe cases used in combination with other agents. They lower blood pressure: Primarily by decreasing cardiac output. Inhibiting the release of renin from kidney.  E.g. Propranolol, atenolol, metoprolol

Selective α 1 - adrenoceptor blockers The selectivity for α 1 -receptors produce less reflex tachycardia than non selective. More effective when given in combination with β-blockers or diuretics. E.g.Prazocin

VASODILATORS

Compensatory Response to Vasodilators

Vasodilators Na nitropruside DiazoxideMinoxidilHdralazine Arterio & venodilator Arteriodilator Site of action Release of nitric oxide (NO) NO→activation of guanylyl cyclase →↑intracellular cGMP Opening of potassium channels Opening of potassium channels in smooth muscle membranes by minoxidil sulfate ( active metabolite ) DirectMechanism of action Intravenous infusion Rapid intravenous Oral Route of admin.

Na nitropruside DiazoxideMinoxidilHdralazine Continue Vasodilators 1.Hpertensive emergency 1.Hypertensive emergency 1.Moderate – severe hypertension 1.Moderate - severe hypertension. Therapeutic uses In combination with diuretic & β-blockers 2.Severe heart failure 2.Treatment of hypoglycemia due to insulinoma 2.correction of baldness 2.Hypertensive pregnant woman

Na nitroprusideDiazoxideMinoxidilHdralazineContinue Vasodilators Severe hypotension Hypotension, reflex tachycardia, palpitation, angina, salt and water retention ( edema) Adverse effects 1.Methemoglobin during infusion 2. Cyanide toxicity 3. Thiocyanate toxicity Inhibit insulin release from β cells of the pancreas causing hyperglycemia Contraindicated in diabetic Hypertrichosis. Contraindicated in females lupus erythematosus like syndrome Specific adverse effects

CALCIUM CHANNEL BLOCKERS

Inhibit calcium influx into arterial smooth muscles & cardiac muscles. Dihydropyridine group (amlodipine, nifedipine) are more selective as arteriodilators ( decreasing afterload) Verapamil &Diltiazem are more selective as cardiac depressant ( decreasing C.O).

Notic Increase the risk of myocardial infarction or mortality in patients receiving short- acting nifedipine for hypertension. It is recommended to use sustained-release calcium blockers or calcium blockers with long half- lives. Intravenous nicardipine or verapamil or diltiazem can be used.

Inhibitors of renin angiotensin system Angiotensin converting enzyme inhibitors (ACEI). Inhibits ACE which lead to : Inhibits the synthesis of angiotensin II. Stimulate the action of Kallikrein-Kinin system.

ACEI Lower blood pressure by decreasing peripheral vascular resistance. No significant change in C.O or heart rate. (Unlike direct vasodilator, no reflex sympathetic activation, so they can be used safely in patients with ischemic heart disease).

Sites of action of ACE inhibitors & Receptor blockers

Pharmacokinetics Captopril, enalapril, moxepril. Absorbed from GIT after oral administration. Food reduce their bioavailability. All are pro-drugs, converted to the active agents by hydrolysis in the liver (Except Captopril). Captopril is short acting(2-3times/daily)

Phrmacokinetics The others are long acting. Enalaprilat is the active metabolite of enalapril is available only for intravenous use for hypertensive emergency. All ACEI are distributed to all tissues except CNS. ACEI are eliminated by the kidney except moexpril.

Clinical uses More effective in treatment of hypertension in conditions associated with high plasma renin activity ( young & white people ). Safely used in patients with ischemic heart disease. Are useful in treating patients with diabetic nephropathy Treatment of heart failure.

Adverse effects Severe hypotension Acute renal failure Hyperkalemia Dry cough, wheezing,and angioedema Captopril may cause loss of taste &in high doses may cause neutropenia, proteinuria,.

Contraindications During the second and third trimesters of pregnancy because of the risk of fetal hypotension,anuria,renal failure, fetal malformations and death. Bilateral renal artery stenosis or stenosis of the artery of a solitary kidney.

Drug interactions With potassium-sparing diuretics NSAIDs impair their hypotensive effects by blocking bradykinin-mediated vasodilatation.

2-Angiotensin receptor – blocking agents Mechanism of action : Block AT 1 receptors. Advantages over ACEI : They have no effect on bradykinin system: No cough,wheezing or angioedema. Complete inhibition of angiotensin action compared with ACEI

Losartan Orally effective Has a potent active metabolite. Long half-life, taken once daily. Can not cross BBB

Adverse effects As ACEI except for cough,wheezing,and angioedema. Same contraindications as ACEI.

Hypertensive Emergency Drugs Sodium nitroprusside Diazoxide Labetalol( α & β blocker ) Nicardipine