Calcium Channel Blockers

Question 1

what are the 3 main CCBs

Answer 1

verapamil
diltiazem 
nifedripine 
all others are analogs of nifedipine 
all block calcium channels but are clinically different

Question 2

CCBs act on 3 main tissues

Answer 2

myocardium
verapamil +++
diltiazem ++
nifedipine 0/+

AV node and conduction system
verap, dilti +++
nife 0

Blood vessels
nife +++
vera ++
dilti +

Question 3

medical uses of CCBs

Answer 3

atrial tachycardias - blocks excess impulses coming through AV node and conduction system (diltiazem or verapamil)

nifedipine-type cause vasodilation and reflex tachycardia (not an anti-arrythmic)

Question 4

CCBs and angina

Answer 4

Diltiazem best for stable angina

CCBs are best for Prinzmetals angina b/c all CCBs relax vasospasm

Question 5

CCBs in hypertension

Answer 5

higher the BP the greater the effect
good for all categories (B blockers aren’t good for elderly or african americans)

threatened miscarriage

Question 6

proposed use of CCBs

Answer 6

migraine (verapamil some effect - blocks initial vasospasm)

tried for prevention of 2nd heart attack

Question 7

Precautions in use of CCBs

Answer 7

dizziness and facial flush from vasodilation
decrease exercise tolerance with verap and diltiazem
constipation
CNS effects (insomnia, nervousness, increase effect of morphine)
short acting CCBs may cause MI - use amlodipine (half life of 39h)
Edema
anti platelet effect –> bruising and petechiae; bleeding in peptic ulcer

Question 8

Molecular mechanisms of CCBs

Answer 8

bind inside channel:
verapamil - phenylalkulamine - voltage-res
nifedipine - dihydropyridine - voltage-sensitive
diltiazem - benzothiazepine - voltage-res

strong voltages in the heart displaces nifedipine, which is why it only has effects on the blood vessels and not the heart

Use dependence: can only get in when channel is open –> seen in verapamil and diltiazem (thats why it is better used when BP is high)

nifedipine blocks right away and is not use dependent

Question 9

nifedipine type CCBs

Answer 9

not plugs
Bay K 8644 opens channels

verapamil may be a plug

Question 10

functions of calcium channel subunits

Answer 10

a2d - cause faster opening/closing
beta - regulates trafficking a1 to membrane (also allows more current after small depolarization)
gamma - present in skeletal muscle channel

Question 11

other calcium channel blockers

Answer 11

Mg++; weak channel blocker, sometimes used in arrhythmias

H+; strong competitor of calcium

barbiturates- block Ca++ channels