Download Antihypertensive Agents

Head Lines
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Etiology
Risk factors
Mechanism
Complications
Treatment
Response mediated by the renin-angiotensin
& sympatheic system on blood pressure
Antihypertensive Agents
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Diuretics
Drugs acting on sympathetic system
Direct vasodilators
Drugs acting on renin-angiotensin
aldosterone system
Calcium channel blockers
DIURETICS
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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
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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
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Clonidine
Stimulate central α2 –adrenoceptors
Decreasing PVR
Useful in hypertension complicated by
renal disease
Sedation & drying of the nasal mucosa
Rebound hypertension
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α-methyl dopa
α2-agonist
Valuable in treating hypertensive patients
with renal insufficiency
In pregnant women
Adrenoceptor –Blocking Agents
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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
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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
VASODILATORS
Compensatory Response to Vasodilators
Vasodilators
Diazoxide
Na
nitropruside
Arteriodilator
Arteriodilator
Arterio &
venodilator
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
Oral
Oral
Rapid
intravenous
Intravenous
infusion
Hdralazine
Site of
action
Mechanism
of action
Route of
admin.
Arteriodilator
Minoxidil
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Vasodilators
Hdralazine
1.Moderate severe
hypertension.
Therapeutic
uses
Minoxidil
1.Moderate –
severe
hypertension
Diazoxide
1.Hypertensive
emergency
Na
nitropruside
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
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Vasodilators
Hdralazine
Minoxidil
Diazoxide
Na nitropruside
Hypotension, reflex tachycardia, palpitation, angina,
salt and water retention ( edema)
Severe
hypotension
lupus
erythematosus
like syndrome
1.Methemoglobin
during infusion
2. Cyanide
toxicity
3. Thiocyanate
toxicity
Adverse effects
Specific
adverse effects
Hypertrichosis.
Inhibit insulin
release from β
cells of the
pancreas
causing
hyperglycemia
Contraindicated
in females
Contraindicated
in diabetic
CALCIUM CHANNEL
BLOCKERS
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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
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Increase the risk of myocardial infarction
or mortality in patients receiving shortacting 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
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Angiotensin converting enzyme inhibitors
(ACEI).
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Inhibits ACE which lead to :
Inhibits the synthesis of angiotensin II.
 Stimulate the action of Kallikrein-Kinin system.
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ACEI
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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
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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
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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
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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
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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
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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
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With potassium-sparing diuretics
NSAIDs impair their hypotensive effects
by blocking bradykinin-mediated
vasodilatation.
2-Angiotensin receptor –
blocking agents
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Mechanism of action :
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Block AT1 receptors.
Advantages over ACEI :
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They have no effect on bradykinin system:
No cough,wheezing or angioedema.
Complete inhibition of angiotensin action
compared with ACEI
Losartan
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Orally effective
Has a potent active metabolite.
Long half-life , taken once daily.
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Can not cross BBB
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Adverse effects
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As ACEI except for cough ,wheezing ,and
angioedema.
Same contraindications as ACEI.
Hypertensive Emergency
Drugs
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Sodium nitroprusside
Diazoxide
Labetalol( α & β blocker )
Nicardipine