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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
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
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
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