Download CALCIUM CHANNEL BLOCKERS (Calcium Antagonists)

CALCIUM CHANNEL BLOCKERS (Calcium Antagonists)
Calcium has important functions in the body, e.g. regulating contraction of cardiac
and smooth muscle and participating the aggregation of platelet. Calcium passes into
cells via tiny “channels” in the membrane (called calcium channel).
Calcium-channel blockers (CCB) are a group of medicines which affect the way
calcium passes into certain cells. They are used to treat various conditions including
high blood pressure, angina, and some arrhythmias, etc.
Ⅰ. Classification
1. IUPHAR（1992）
I: Selectively Block L type Calcium Channels:
Ia: Dihydropyridines：nifedipine、nimoldipine 、nicardipine
Ib:Benzothiazepines：diltiazem
Ic: Phenylalkylamines：verapamil
II: Selectively Block other type Calcium Channels：
III: Non Selective Calcium Channel Blockers:
Flunarizine，Prenylamines
2. According to the applying time of drugs:
First-generation: verapamil、nifedipine、 diltiazem
Second- generation : felodipine、nimoldipine 、nicardipine et al
Third-generation : pranidipine、 amlodipine et al
Pharmacological actions
1) Effects on heart
a. Negative inotropic effect
b. Negative chronotropic\frequency action and negative dromotropic effect
c. Protective effect on myocytes
2) Effects on Vascular Smooth Muscle
* Relaxation in arterial smooth muscle → decreased cardiac afterload (aortic
pressure)
* Little or no effect on venous beds → no effect on cardiac preload (ventricular
filling pressure)
* Specific dihydropyridines may exhibit greater potencies in some special vascular
beds (e.g.- nimodipine more selective for cerebral blood vessels)
& Hemodynamic Effects：
All of the clinically-approved CCB:
* Decrease coronary vascular resistance and increase coronary blood flow
* Decrease peripheral resistance via vasodilatation of arteries
* Are no significant effect on venous tone at normal doses
Drug-Specific Effects
Dihydropyridines (e.g. nifedipine, nicardipine, and nimodipine)
*Vasodilatation of arterial resistance vessels
*a reflex increase in sympathetic response
*The overall hemodynamic effect is a drop in blood pressure, an increase in heart rate
and contractility, and an increase in cardiac output.
Verapamil
*has greater direct negative effects to heart than the dihydropyridines
*resulting in a drop in heart rate
*resulting in a lowering of myocardial contractility
Diltiazem
*The hemodynamic effects of diltiazem are intermediate between the
dihydropyridines and verapamil
*The drug causes a modest lowering of heart rate and modest decrease in myocardial
contractility, both of which are less than verapamil for a given drop in blood pressure
3) Effects on other SM：relax bronchial SM > gastrointestinal SM、ureter and uterus
SM
4) other effects:
Antiatherosclerotic effects
Effects on the structure and function of red cells and platelets.
Effects on the renal function
Clinical Uses
(1) The primary indications for the Calcium channel blockers are
* Hypertension * Angina * Arrhythmias
(2)Cerebralvascular disease (nimodipine, Flunarizine): cerebral vasospasm,cerebral
embolism, cerebral ischemia.
(3) Others: Radynau’s disease; Bronchial asthma; Migraine; Atherosclerosis
Toxicities and Side Effects
* The calcium channel blockers are generally well-tolerated .
* The most common side effects are due to excessive vasodilatation (i.e.- dizziness,
hypotension, headache, flushing etc.) , the other side effect is constipation.
* Serious toxic effects
bradycardia, AV block, transient asystole, exacerbation of heart failure are rare and
usually occur under specific conditions. Patients with moderate to severe ventricular
dysfunction, SA node or AV conduction disturbances, and systolic blood pressures
below 90 mm Hg should not be treated with verapamil or diltiazem.