Download Calcium Channel Antagonists

Calcium Channel Antagonists
Drug
Verapamil
(phenylalkylamine)
Nifedipine
Nicardipine
Nimodipine
Nitrendipine
Isradipine
Amlodipine
(dihydropyridine)
Diltiazem
(benzothiazepine)
MOA
 calcium channel blocking agent that
inhibits the movement of calcium ions
across cell membranes of arterial
smooth muscle and cardiac muscle
 reduced influx of calcium ions results in
a relaxation of arterial smooth muscle
and negative inotropy
 reduces afterload, dilates the main
coronary arteries and arterioles, and
inhibits coronary artery spasm. The
negative inotropic effect is offset by the
decrease in afterload and a reflex
increase in adrenergic tone
 inhibition of calcium ion movement also
results in prolongation of the
atrioventricular (AV) nodal effective
refractory period and slowed AV
conduction
 dihydropyridine calcium channel
blocking agents
 selectively inhibits calcium influx across
cell membranes in cardiac and vascular
smooth muscle, with a greater effect on
vascular smooth muscle
 peripheral arteriolar vasodilator; thus it
reduces afterload
 calcium channel blocking agent that
inhibits the influx of calcium ions into
cell membranes of vascular smooth
muscle and cardiac muscle
 on vascular smooth muscle results in a
decrease in peripheral vascular
resistance and a consequent reduction in
blood pressure with a slight reduction in
heart rate
 decreases conduction through the
sinoatrial (SA) and atrioventricular
(AV) nodes, produces small increases in
the PR interval, and reduces the renal
and peripheral effects of angiotensin II
 greater effect on coronary circ. than on
other vascular beds
Pharmacokinetics
 oral
 onset of action: 30 min.
(IV - <2 min.)
 plasma t ½ 4-12 hr
 hepatic metabolism and
elim.
 primarily renal excretion
Toxicity
severe heart block (if IV with
beta antagonist or dig
toxicity)
myocardial depression
hypotension
if given with dig, may cause
dig toxicity
SE: constipation, N,
dizziness, flushing, pedal
edema
Clinical Use
SVT, A-fib, A-flutter,
angina, hypertrophic
cardiomyopathy,
hypertension, and
Raynaud’s Syndrome
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oral
onset of action: 20 min.
(sublingual – 3 min.)
plasma t ½ 2-4 hr
primarily renal excretion
hypotension
SE: dizziness, flushing, HA,
palpitations, rare
exacerbation of angina, pedal
edema
angina, hypertension,
Raynaud’s Syndrome
(and peripheral
vascular disease)
no useful antiarrhythmic
properties
oral
onset of action: 30-60
min.
plasma t ½ 3-7 hr
hepatic metabolism
fecal elim.
bradycardia
depression of AV nodal
conduction
SE: HA, flushing, dizziness
angina, SVT, A-fib,
A-flutter,
hypertension,
Raynaud’s
Syndrome; inhibits
platelet aggregation
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Bepridil
combine potent non-calcium related effects
(fast Na+ channel inhibition and inhibition of
calmodulin)
tx for refractory
angina, but can cause
life-threatening
arrythmias (can
prolong QT interval
and can cause
torsades de pointes in
those with hypo-K+
Mibefradil
produces coronary and peripheral
vasodilation
decreases heart rate, but does not decrease
myocardial contractility
tx of HTN and
chronic stable angina
the pharm. syllabus says that we are not responsible for bepridil or mebefradil