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8/3/2019 Ca2+ Channel Block
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CaCa2+2+ Channel BlockChannel Block
Donnah Laizabeth A. Dones
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The major electrophysiological effects
resulting from block of cardiac Ca2+
channels are in slow-response tissues:
a. sinus nodes
b. AV nodes.
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nifedipine
Dihydropyridines
used commonly in angina and hypertension
preferentially block Ca
2+
channels in vascularsmooth muscle;
their cardiac electrophysiological effects,
such as heart rate acceleration, result
principally from reflex sympathetic activationsecondary to peripheral vasodilation.
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verapamil, diltiazem, and
bepridil block Ca2+ channels in cardiac cells at clinically useddoses.
These drugs generally slow heart rate although
hypotension, if marked, can cause reflex sympatheticactivation and tachycardia.
The velocity of AV nodal conduction decreases,sothe PR interval increases.
AV nodal block -occurs as a result of decrementalconduction, as well as increased AV nodalrefractoriness.
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Another important indication forantiarrhythmic therapy is to reduceventricular rate in atrial flutter or
fibr
illat
ion
.
Unlike adrenergic receptor antagonists,Ca2+
channel blockers have not been shown toreduce mortality after myocardialinfarction (Singh, 1990).
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Bepridil
increases action potential duration in
many tissues
can exert an antiarrhythmic effect in atriaand ventricles.
However, it can cause torsades de pointes
it is not prescribed widely and has beendiscontinued in the United States.
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Verapamil and Diltiazem
The major adverse effect ofintravenous verapamilor diltiazem is hypotension,particularly with bolusadministration.
Hypotension - is a particular problem if the drugs are used mistakenly in
patients with ventricular tachycardia (in which Ca2+
channel blockers usually are not effective) misdiagnosedas AV nodal re-entrant tachycardia (Stewart et al., 1986).
-also is frequent in patients receiving other vasodilators,including quinidine, and in patients with underlying leftventricular dysfunction, which the drugs can exacerbate.
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Parenteral verapamil and diltiazem-
approved for rapid conversion of PSVTs tosinus rhythm and for temporary control of
rapid ventricular rate in atrial flutter or
fibrillation.
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Severe sinus bradycardia or AV block
also occurs, especially in susceptible
patients, such as those also receiving
blockers.
With oral therapy, these adverse effects
tend to be less severe.
Constipation can occur with oral
verapamil
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Verapamil
(CALAN, ISOPTIN, VERELAN, COVERA-HS) isprescribed as a racemate.
L
-Verapamil is a more potent calcium channelblocker than is D-verapamil.
However, with oral therapy, the L-enantiomerundergoes more extensive first-pass hepatic
metabolism. --For this reason, a givenconcentration of verapamil prolongs the PRinterval to a greater extent when administeredintravenously than when administered orally
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Oral verapamil
- may be used in conjunction with digoxin to
control ventricular rate in chronic atrial flutter
or fibrillation
for prophylaxis of repetitive PSVT.
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Diltiazem
(CARDIZEM, TIAZAC, DILACORXR, and
others)
also undergoes extensive first-pass
hepatic metabolism
have metabolites that exert Ca2+ channel
blocking actions.
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In clinical practice, adverse effects during therapy withverapamil or diltiazem are determined largely by:
a. underlying heart disease
b. concomitant therapy
plasma concentrations of these agents are notmeasured routinely
Both drugs can increase serum digoxin concentration,although the magnitude of this effect is variable
excess slowing of ventricular response may occur inpatients with atrial fibrillation.