Calcium channel blockers Flashcards
block sodium
lidocaine
-fast
block calcium
calcium channel blockers
-slow
calcium channel blockers
- verapamil (phenylalkylamine)
- diltiazem(benzothiazepine)
- nifedipine (dihydropyridine)
- all others CCB analogs of nifedipine
- all block calcium channels
3 tissues calcium channel blockers act on
- myocardium
- AV node and conducting system
- blood vessels
myocardium CCB
verapamil +++
diltiazem ++
nifedipine 0/+
AV node and conducting system CCB
verapamil, diltiazem +++
nifedipine 0
blood vessels CCB
nifedipine +++
verapamil ++
diltiazem +
medical use of CCB
- atrial tachycardias (flutter, fib)
- stable angina
- prinzmetals angina
- hypertension
CCB use in: atrial tachycardias
- blocks excess impulses coming through AV node and conducting system
- diltiazem or verapamil used
- nifedipine-type cause vasodilation and reflex tachycardia
CCB use in: stable angina
exercise related
- diltiazem best ?
- verapamil depressed heart too much
- nifedipine type cases reflex tachycardia
CCB use in: prinzmetals angina
non-exercise related
- best drugs for variant angina, all relax skeletal muscle
- all CCB’s relax vasospams
- blood vessels most affected: brain, heart, skeletal muscle
- beta-blockers not very effective
CCB use in: hypertension
- higher the blood pressure, greater the effect
- good for all categories
- beta-blockers not so good in elderly or in AA
- CCBs more effect in elderly
- no effect on blood lipids
CCB use in: threatened miscarriage
- prematurity still major cause infant death
- calcium channel in uterus
- nifedipine effective
proposed use for CCB
Migraine
-verapamil some effect
-block initial vasospam
tried for prevention of 2nd heart attack
precautions in use of CCB’s
- most common complaint from vasodilation: dizziness, facial flush
- decrease exercise tolerance verapamil, diltiazem - constipation: elderly
- CNS effects: insomnia, nervousness, increase effect of morphine
- edema: dilate arteries not veins, increase capillary pressure (occurs in 11% of patients taking nifedipine)
- anti-platelet effect: bruising, petechiae (on hand), bleeding in peptic ulcer
what can short acting CCBs cause?
worsen angina and cause MI
-use amlodipine (half-life 39 hours)
MOA of CCB
- bind inside channel
- different CCB act on different sites, explains lack os SAR
- binding a function of voltage for nifedipine type
why doesn’t nifedipine have an effect on the heart?
- binding a function of voltage for nifedipine type
- strong voltage fluctuations in heart displace drug-> not so in blood vessels
- -voltage change causes decrease in affinity for receptor
“use dependence” CCB means?
- verapamil can get in only when channel opened electrically (use dependence)
- diltiazem also somewhat use-dependent
- explains why these drugs better when BP is high
- nifedipine blocks right away, no need to depolarize
when can nifedipine bind CC?
when calcium channel is inactive
- not plugs
- analog: Bay K 8644, open channels
when can verapamil bind CC?
when calcium channel is open
-may be a plug
binding sites for CCB
- explains slow calcium entry
- explains ions selectivity
new designation of Calcium channel: L
Ca1 family
-Ca 1.2 in heart and blood vessels
new designation of Calcium channel: T
Ca3 family
- regulate electrical excitability in many tissues
- can enhance amplitude of depolarization in heart, neurons
new designation of Calcium channel: P/Q, N
Ca2 family
-Ca 2.1-> P/Q purkinje
Ca 2.3-> N neuronal
-regulate neurotransmitter release in brain
VSCC
mutlimeric proteins
-alpha-1 subunit forms the pore and contains drug binding sites
functions of calcium channel subunits
- alpha-2-gamma: cause faster opening/closing
- beta: regulates trafficking alpha-1 to membrane, also allows more current after small depolarization
- gamma: present in skeletal muscle channel but rarely elsewhere
other CCB
- Magnesium
- weak channel blocker
- sometimes used in arrhythmias - Hydrogen
- strong competitor of calcium
- but some drugs don’t work well at low pH - older drugs: Barbiturates
