Lecture 10: Calcium channel blockers Flashcards
3 different classes of CCB
Phenylalkylamines (verapamil),
Benzothiazepines (diltiazem),
1-4 dihydropyridines (nifedipine and amlodipine)
Selectivity of CCBs
Verapamil and Diltiazem for cardiac cells
Nifedipine and amlodipine for arterial muscle cells
Phenylalkylamines
Verapamil works on cardiac cells
Benzothiazepines
Diltiazem works on cardiac cells
1,4-dihydropyridines
Nifedipine and Amlodipine work on arterial muscle cells. Amlodipine has a slow onset and slow affect
Amlodipine
additional prototype of 1,4-dihydropyridine
slow onset, slow affect as compared to others in this class
Uses for CCBs
- Angina pectoris
- Hypertension
- Treatment of supraventricular arrhythmias (atrial flutter, atrial fibrillation, paroxysmal SVT)
Use dependent binding
Targets cardiac cells. Inside the channel. Verapamil and Diltiazem.
Voltage-dependent binding
Targets smooth muscles. Outside of channel. Nifedipine and amlodipine?
Mechanisms of action
Increase the time that Ca2+ channels are non-conducting
Relaxation of the arterial smooth muscle but not much effect on venous smooth muscle.
Significant reduction in afterload but not preload
Do CCBs act on neurons?
No. B/c N type and P type Ca2+ channels mediate neurotransmitter release in neurons
Do CCBs act on skeletal muscles?
No. Skeletal muscle relies on intracellular Ca2+ for contraction but can still contract without extracellular Ca2+
Do CCBs act on cardiac cells?
Yes. Cardiac cells rely on L-type Ca2+ channels for contraction and for upstroke of teh AP in slow response cells
Do CCBs act on vascular smooth muscle
Yes. Vascular smooth muscle relies on Ca2+ influx through L-type Ca2+ channels for contraction
Effects of Dihydropyridines
- Peripheral vasodilation
- Reflex in HR, myocardial contractility, and O2 demand (sympathetic stimulation), more present in nifedipine rather than amlodipine (due to shorter half life)
- Coronary vasodilation
