ANTI-DIABETIC DRUGS Assoc. Prof. Iv. Lambev E-mail: [email protected] .
Calcium antagonists (Summary) Dr Ivan Lambev ([email protected])
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Transcript of Calcium antagonists (Summary) Dr Ivan Lambev ([email protected])
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Calcium antagonists(calcium channel blockers)
They block calcium influx through voltage-dependant calcium channels in the smoothmuscles. They dilatecoronaries andperipheral arteriesand reduceheart afterload.
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VDCC ROCC
Receptor
AP
Ca2+
Ca2+
Sarcoplasmaticreticulum
Cellwall
NA
(–)
Calciumantagonists
AP – action potential, NA – noradrenalineVDCC – voltage-dependent calcium channelsROCC – receptor operating calcium channels
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Regulation of intracellular calcium
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In the cell membranes there 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-typecalcium channels, localized in the myocardiumand myocytesof bloodvessels.L-type channelsare connectedto the plateauof the AP.
Plateau phase of AP
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Calcium antagonists reduce coronary and peripheral vascular resistance, decreaseblood pressure and myocardial oxygenconsumption.
Dihydropyridines (nifedipine, amlodipine,etc) don’t have cardionegative inotropic, chronotropic, and dromotropic effect incomparison with verapamil and diltiazem.
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Dihydropyridines ● Norm frequent (with normal heart rate) and24-hours long effect: Amlodipine, Felodipine ● Other dihydropyridines produce tachycardia (increase baroreflex sensibility): Isradipine, Lacidipine, Nicardipine, Nifedipine, Nisoldipine, Nitrendipine ● cerebral vasodilators (Nimodipine) Phenylalkylamines: Verapamil Benzotiazepines: Diltiazem Flunarizine type (cerebral vasodilators) Cinnarizine, Flunarizine
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Arterial hypertensiona) Dihydropyridinesb) Verapamil and Diltiazem
Coronary heart diseasea) Dihydropyridinesb) Verapamil and Diltiazem
Ischemic cerebral strokeCinnarizine, Flunarizine, Nimodipine
SV tachyarrhythmias: Verapamil, Diltiazem (i.v.) Migraine (in remission periods)
Flunarizine, Verapamil
Beta-blockers + dihydropyridines: YES (OK)Beta-blockers + Verapamil or Diltiazem = NO
Mai
n in
dica
tions
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Cal
cium
an t
agon
ists
Amlodipine norm frequent dihydropyridinet1/2 31–47 h, 55–91% p.o. bioavailability5–10 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. bioаvailability, first pass effect –extensive liver metabolism)
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Class IV antiarrhythmic drugs
Indications: SV tachyar- rhythmias
ARs: headache, ankle swelling,bradycardia, AV block, negativeinotropic effect (decreasingcardiac contractility)
Mainly verapamil (p. o./i. v.) and diltiazem (only i.v.) has specific action on ..the… SA and AV node (they shorten AP)
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Atrial flutter with a 4:1 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