Download Ca-Channel blockers:

Ca-Channel blockers:
 They do not affect serum lipid
concentrations
 Not cause sexual dysfunction.
 Diuretics enhance the efficacy of Cachannel blockers.
Mechanism of action: Amlodipine, diltiazem,
verapamil, felodipine, isradipine, nifedipine and
nicardipine induce vasodilation and decrease
peripheral resistance.
2. Pharmacologic effects:
a. Verapamil, amlodipine, and diltiazem
cause little change in heart rate, whereas the
dehydropyridines produce an initial increase,
which is reflex-mediated.
b. Diltiazem and verapamil depress A-V
conduction and should not be used with beta
blockers.
3. Adverse effects: Verapamil can cause
severe constipation.
Vasodilators:
decrease peripheral vascular resistance and
arterial blood pressure.
a. Their effect compensated by reflex
sympathetic activity.
b. They increase plasma renin activity.
c. causes salt and water retention.
d used in conjunction with diuretic and beta
adrenergic blocking therapy.
Hydralazine:
a. Pharmacokinetics
(1) given orally (long treatment) or IM.
(2) It is subjected to first-pass hepatic
metabolism.
(3) It is metabolized by several pathways,
including acetylation, which is subject to
genetic variation.
(4) Its duration of effect ranges from 2-6 hours.
(5) Tolerance develops after 24 months of
therapy.
b. Therapeutic uses:
(1) It is used to treat moderate to severe
hypertension.
(2) It is used in the treatment of acute and
chronic CHF.
c. Route of administration:
(1) must be combined with beta-blocker to
prevent tachycardia and increased renin
secretion resulting from reflex sympathetic
stimulation.
(2) Oral hydralazine is combined with diuretic
agent to prevent salt and water retention.
Minoxidil:
Potent than hydralazine. It decreases renal
vascular resistance with no effect on renal
blood flow.
It is orally administered, excreted with urine.
Used to treat sever hypertension (associated
with renal impairment).
It should be coupled with beta-blockers and
diuretic to overcome sympathetic activation and
salt retention.
Adverse effects: pericardial effusion and
tamponade in patients with renal impairment.
Hirsutism occurs with no virilism or other
endocrine abnormalities.
Diazoxide:
Reduce both systolic and diastolic pressure,
inducing sympathetic activation.
It relaxes other smooth muscle.
It inhibits the release of insulin.
Uses,
Intravenous diazoxide is used for hypertensive
emergencies.
Diazoxide used orally to treat hypoglycemia
that is caused by hyperinsulinemia.
Diazoxide is given by rapid injection into a
peripheral vein.
Adverse effects
(1) Severe hypotension.
(2) Its reflex sympathetic stimulation can cause
angina and worsen myocardial ischemia.
(3) It inhibits the release of insulin and can
produce hyperglycemia.
(4) Edema caused by the retention of salt and
water.
Non selective (Arterial and venous
vasodilators): These drugs reduce both arterial
resistance and venous tone and markedly
decrease arterial blood pressure.
1. Sodium nitroprusside
Onset of action within 1 minute of IV.
administration, duration within 5 minutes.
It is rapidly inactivated by hepatic enzymes,
first to cyanide and then to thiocyanate.
No effect on other smooth muscle.
Decreases myocardial oxygen demand.
Renal blood flow is maintained with
nitroprusside, and renin secretion is increased.
Uses
(1) Nitroprusside, used in hypertensive
emergencies. It is preferable to diazoxide in
patients with coronary insufficiency
or pulmonary edema because, in contrast to
diazoxide, it reduces cardiac preload and
myocardial oxygen demand.
(2) Used to produce controlled hypotension to
minimize bleeding during surgery.
(3) Nitroprusside can improve left ventricular
function in patients with acute myocardial
infarction and has benefit in the treatment of
acute CHF.
Route of administration
(1) Na-nitroprusside is administered only as an
intravenous infusion with sterile 5% dextrose in
water. Once prepared, the solution must be
protected from light and used within 4 hours.
(2) Blood pressure must be monitored
continuously while the drug is being given.
Adverse effects
(1) Hypotension, nausea, diaphoresis,
headache, restlessness, palpitations, and
retrosternal pain can occur secondary to
excessive, rapid vasodilation.
(2) It is metabolized to cyanide and to
thiocyanate. cyanide toxicity can occur.
(3) Accumulated thiocyanate during prolonged
nitroprusside therapy, especially in patients
with poor renal function greater than 10 mg/dl
can cause weakness/ nausea/ muscle spasms
and psychosis, as well as hypothyroidism
caused by interference with iodine transport.
2. Prazosin: is a selective postsynaptic α one
adrenergic receptor blocking agent that causes
vasodilation of both the arteries and veins.
a. Pharmacokinetics
(1) Plasma half-life is usually 2-3 hours but can
be prolonged by CHF.
(2) Undergo significant first-pass metabolism. It
is excreted in the feces and bile.
b. Pharmacologic effects
(1) it reduces peripheral vascular resistance.
(2) Unlike nonselective α-adrenergic blockers,
prazosin does not usually produce reflex
tachycardia.
(3) Unlike beta blockers, prazosin does not
adversely affect insulin sensitivity or blood
lipids.
(4) It does not increase plasma renin activity.
(5) Prazosin produces minimal changes in
cardiac output, renal blood flow, and glomerular
filtration rate.
Therapeutic uses of prazosin:
(1) treatment of mild to moderate hypertension
alone or in combination., more effective in
conjunction with a diuretic or an α-adrenergic
blocking agent.
(2) treatment of acute CHF.
Route of administration: orally,2-3 times daily.
Adverse effects
(1) Dizziness, headache, drowsiness and
palpitations can occur but disappear with
continued therapy.
(2) prazosin larger than 1 mg can induce
postural hypotension and syncope due to a
decreased venous return to the heart.
(3) antinuclear factor become positive.
3. Terazosin is similar to prazosin with longer
t1/2 (12 hours) and duration (24 hours).
Terazosin is used to treat benign prostatic
hyperplasia as well as hypertension.
Mechanism of action: Terazosin is an αpostsynaptic adrenoreceptor blocker that
rapidly relaxes smooth muscle tone in the
arteries, bladder neck, prostate capsule and
prostatic urethra.
Pharmacokinetics
rapidly and completely absorbed orally.
(2) metabolized by the liver and excreted
mainly in bile.
Adverse effects:
(1) Orthostatic hypotension and syncope.
(2) Other adverse effects associated with αadrenergic blockers may occur, including nasal
congestion and impotence.
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