Calcium Channel Blockers Flashcards
name 3 instances in which calcium channel blockers are indicated?
- first-line for HTN
- ischemic heart disease (reduced O2 demand)
- anti-arrhythmic (block conduction of AV node)
_____ channels protect distal capillary beds from high pressure
stretch-activated L-type calcium channels
*note then that calcium channel blockers can cause edema by increased hydrostatic pressure in capillary beds
what is the downstream signaling molecule following activation of the following:
a. alpha1 receptor
b. beta2 receptor
c. NO diffusion into cell
a. alpha1 receptor —> PLC —> IP3 —> Ca2+ release from SR —> MLCK
b. beta2 receptor —> adenylyl cyclase —> cAMP —> PKA —> BLOCK MLCK
c. NO diffusion into cell —> cGMP —> PKG —> MLCP (phosphatase)
calcium channel blockers (CCBs) bind L-type calcium channels primarily in what kind of blood vessels?
block voltage and mechanical-gated L-type Ca2+ channels in myocardium (negative chronotropy/inotropy)
and primarily arterial vascular smooth muscle (reduce afterload)
how do calcium channel blockers lower chronotropy in myocardium?
block voltage-gated L-type calcium channels —> shorten plateau phase of action potential —> AP duration is shorter
also decreases force of contraction (directly related to Ca2+ concentration)
how do Ca2+ channel blockers affect the following?
a. SA node
b. AV node
c. ventricular myocardium
d. coronary arteries
e. arterioles
f. peripheral veins
a. SA node —> decrease HR & O2 demand
b. AV node —> decrease conduction
c. ventricular myocardium —> decreased contractibility & O2 demand
d. coronary arteries —> increased vasodilation & O2 supply
e. arterioles —> decreased afterload (BP) & O2 demand (myocardial)
f. peripheral veins —> minimal vasodilation
where do the following types of calcium channel blockers exert their preference?
a. dihydropyridines
b. phenylalkylamines
c. benzothiazepines
a. dihydropyridines (Nifedipine, Amlodipine) - vascular smooth muscle (primarily arterial)
b. phenylalkylamines (Verapamil) - heart
c. benzothiazepines (Diltiazem) - heart
*note that in high enough doses, effects of all kinds are systemic
match Amlodipine, Nimodipine, Nifedipine, and Clevidipine with:
prototype drug, IV only, long t1/2, partially selective for cerebral vessels
what kind of drugs are these?
these are all dihydropyridine calcium channel blockers (preference for vascular smooth muscle, mostly arterial)
Nifedipine - prototype
Amlodipine - long half life (t1/2)
Clevidipine - IV only
Nimodipine - cerebral vessels
match Verapamil and Diltiazem
with benzothiazepine and phenylalkylamine
what do these drugs do?
these are calcium channel blockers with preference for the heart
Verapamil is a phenylalkylamine
Diltiazem is a benzothiazepine
what class of drug does this describe, and name the prototype drug in this class:
- calcium channel inhibitors
- selective vasodilators for arterioles > veins
dihydropyridines
prototype: nifedipine
long acting (more commonly used): amlodipine
what are the clinical uses of dihydropyridines (4)? what cautions should be taken with prescribing them?
dihydropyridines: calcium channel blockers selective for arterioles (—> vasodilation)
uses: DOC for essential HTN, acute hypertensive emergency (Clevidipine - IV only), chronic stable angina (decrease afterload), subarachnoid hemorrhage (nimodipine - selective for cerebral vessels)
caution with effects of acute vasodilation (less problematic with long-active drugs like amlodipine): headache/dizziness, flushing, peripheral edema, gingival hyperplasia (may inhibit apoptosis of endothelial cells), increased SNS/HR (nifedipine)
what is the #1 calcium channel blocker for reducing heart rate through the AV node?
Verapamil: acts on the AV node to reduce heart rate
non-dihydropyridine L-type calcium channel blocker
what are the indications for non-dihydropyridine calcium channel blockers (CCBs)? (2)
what cautions should be taken with prescribing?
recall non-dihydropyridine Ca2+ channel blockers act on the heart
- supraventricular tachyarrhthmias (Verapamil) - stable patients only
- second-line for stable angina
caution: negative inotropy worsening HF, worsening AV block (contraindicated with beta blockers - severe negative inotropy), constipation (peripheral Ca2+ channel blockage)
what can occur from calcium channel blocker poisoning, and what is the treatment?
Verapamil and Diltiazem OD (act on heart) —> hypotension, bradycardia
at high enough doses, all types of CCBs cause problems related to peripheral vasodilation, decreased inotropy, bradycardia, hyperglycemia (reduced insulin secretion)
treat with calcium
