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 α2 –adrenoceptors

Decreasing PVR Useful in hypertension complicated by

renal disease Sedation & drying of the nasal mucosa Rebound hypertension

Continue α-methyl dopa α2-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 α1- adrenoceptor blockers The selectivity for α1-receptors produce

less reflex tachycardia than non selective. More effective when given in combination

with β-blockers or diuretics. E.g.Prazocin

VASODILATORSVASODILATORS

Compensatory Response to Vasodilators

VasodilatorsHdralazin

eMinoxidil Diazoxid

eNa

nitropruside

Site of action

Arteriodilator Arteriodilator Arteriodilator Arterio & venodilator

Mechanism of action

Direct Opening of potassium channels in smooth muscle membranes by minoxidil sulfate ( active metabolite )

Opening of potassium channels

Release of nitric oxide (NO) NO→activation of guanylyl cyclase →↑intracellular cGMP

Route of admin.

Oral Oral Rapid intravenous

Intravenous infusion

ContinueVasodilators

Hdralazine Minoxidil Diazoxide Na nitropruside

Therapeutic uses

1.Moderate -severe hypertension.

1.Moderate –severe hypertension

1.Hypertensive emergency

1.Hpertensive emergency

In combination with diuretic & β-blockers

2.Hypertensive pregnant woman

2.correction of baldness

2.Treatment of hypoglycemia due to insulinoma

2.Severe heart failure

ContinueVasodilators

Hdralazine Minoxidil Diazoxide Na nitropruside

Adverse effects

Hypotension, reflex tachycardia, palpitation, angina, salt and water retention ( edema)

Severe hypotension

Specific adverse effects

lupus erythematosus like syndrome

Hypertrichosis.

Contraindicated in females

Inhibit insulin release from β cells of the pancreas causing hyperglycemia

Contraindicated in diabetic

1.Methemoglobinduring infusion2. Cyanide toxicity3. Thiocyanate toxicity

CALCIUM CHANNEL CALCIUM CHANNEL BLOCKERSBLOCKERS

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 blockersSites 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 AT1 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