Calcium antagonists

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Calcium antagonists (Summary)

Dr Ivan Lambev (itlambev_at_mail.bg)
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Calcium antagonists (calcium channel blockers)
They block calcium influx through
voltage- dependant calcium channels in the
smooth muscles. They dilate coronaries
and peripheral arteries and reduce heart
afterload.
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Calcium antagonists
AP
NA
Ca2
()
Receptor
Cell wall
VDCC
ROCC
Ca2
Sarcoplasmatic reticulum
AP action potential, NA noradrenaline VDCC
voltage-dependent calcium channels ROCC
receptor operating calcium channels
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Regulation of intracelullular calcium
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• In the cell membranes their are
• three types of calcium channels
• Voltage-dependent (L, N, O, P, Q, R, T)
• ? Receptor operating
• ? Stretch activated

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Calcium antagonists block predominantly
L-type calcium channels, localized in
myocardium and myocytes of blood vessels. L-type
channels are connected to the plateau of the AP.
Plateau phase of AP
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Calcium antagonists reduce coronary and
peripheral vascular resistance, decrease blood
pressure and myocardial oxygen consumption.
Dihydropyridines (nifedipine, amlodipine
etc) dont have negative inotropic,
chrono- tropic and dromotropic effect in
comparison to verapamil and diltiazem, which
increase baroreflex sensibility.
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? Dihydropyridines ? Norm frequent (with
normal heart rate) and 24-hours long effect
Amlodipine, Felodipine ? Other
dihydropyridines produce tachycardia
(increase baroreflex sensibility)
Isradipine, Lacidipine, Nicardipine,
Nifedipine, Nimodipine, Nisoldipine,
Nitrendipine ? Phenylalkylamines Verapamil SR
? Benzotiazepines Diltiazem SR ? Flunarizine
type Cinnarizine, Flunarizine
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? Arterial hypertension a) Dihydropyridines b)
Verapamil SR and Diltiazem SR ? Coronary heart
disease a) Dihydropyridines b) Verapamil SR and
Diltiazem SR ? Ischemic cerebral
stroke Cinnarizine, Flunarizine, Nimodipine ? SV
tachyarrhythmias Verapamil, Diltiazem (i.v.) ?
Migraine (in remission periods) Flunarizine,
Verapamil
Main indications
Beta-blockers dihydropyridines YES
(OK) Beta-blockers Verapamil or Diltiazem NO
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Amlodipine norm frequent dihydropyridine t1/2
3147 h, 5591 p.o. bioavailability 510 mg/24 h
p.o. (once daily) Nifedipine (tachycardia!)
effective in vasospastic angina Diltiazem (in SR
dosage forms) Verapamil (Isoptin SR tabl. 240
mg) (22 p.o. bio?vailability, first pass effect
extensive liver metabolism)
Calcium antagonists
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Class IV antiarrhythmic drugs
?Mainly verapamil (p. o./i. v.) and diltiazem
(only i.v.) has specific action on SA and AV
node (they shorten AP)
ARs headache, ankle swelling, bradycardia, AV
block, negative inotropic effect
(decreasing cardiac contractility)
?Indications SV tachyar- rhythmias
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Atrial flutter with a 41 conduction ratio.
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• ARs of calcium antagonists
• Arterial dilation headache, flush, dizziness,
• ankle swelling (resistant to treatment with
• diuretics but not with ACE inhibitors).
• Bradycardia and AV block (verapamil).
• Verapamil beta-blockers potentiate
• cardiodepression.
• Tachycardia (nifedipine, nisoldipine).
• Constipation (verapamil 8 nifedipine 3)
• Haemorrhagic gingivitis