Calcium Channel Blockers

Question 1

role of calcium in cardiac and smooth muscle

Answer 1

changes in intracellular calcium regulates contraction through different mechanisms in cardiac and smooth muscle
Excitation- contraction coupling is the process in which calcium channels are activated and exert their effects.

Question 2

Six tyoes of Calcium channels

Answer 2

L,N,P,Q,R,T

Question 3

L type channels

Answer 3

sustained conductance, slow inactivation

Question 4

T type channels

Answer 4

similr to L but rapid inactivation, minimal sensitivity to CCB

Question 5

5 subunits of L type channels

Answer 5

Alpha 1, alpha 2, beta, gamma, and delta

Question 6

how do phenylalkylamines work?

Answer 6

verapamil

bind to intracellular portion of alpha 1 subunit

Question 7

how do benzothiazepines work?

Answer 7

diltiazem

mechanism not well understood

Question 8

how do 1,4-dihydropyridines work?

Answer 8

modulate the L-type channel, vascular smooth muscle

Question 9

what are the 5 major classes of CCB?

Answer 9

benzothiazeprines: Diltizem
DHP: Nicardipine, nifedipine, nimodipine, clevidipine, amlodipine
Phenylalkylamines: Verapamil
Diarylaminopropylamine ethers: bepridil
Benzimidazole- substituted tetralines: mibefradil

Question 10

Pharm of Non-dihydropyridines

Answer 10

negative inotropic effect
negative chronotropic effect
negative dromotropic effect
positive lusitropic effect

Question 11

Pharmacology of ALL CCB

Answer 11

decrease coronary vascular resistance and increase coronary blood flow
decrease PVR via vasodilation of arterioles
are without significant effect on venous tone at normal doses

Question 12

common indications for CCB

Answer 12

Variant angina: prinzmetal
Exertional angina: due to fixed coronary vascular obstruction, BB with DHP to avoid reflex tachy
unstable angina: reduces O2 consumption, eliminates incidental vasospasm
Arrythmias: controlling PSVT, extreme caustion with WPW
HTN
Subarachnoid hemorrhage
hypertrophic cardiomyopathy: Nifedipine and verapamil

Question 13

Common side effects

Answer 13

orthostatic hypotension, bradycardia, peripheral edema, dizziness, headaches, flushing, N/V

Question 14

cautions with CCB

Answer 14

aggravation of MI,
verapamil can increase serum dig levels
AV blocks can occur with concominent use of BB
AV blocks can occur with dig and CCB

Question 15

DHP

Answer 15

Nifedipine, Nicardipine, Nimodipine
vasodilation of arterial resistance vessels
Weak SA node and AV junction, there is an increase in heart rate due to the increase in sympathetic tone mediated by the baroreceptor reflex
Overall hemodynamic response drop in Bp, and increase in HR and contractility, and an increase in CO

Question 16

Nicardipine

Answer 16

DHP, commonly used in OR, can be given IV bolus or continuous

Question 17

Clevidipine

Answer 17

DHP, very fast onset and offset, faster than nicardipine, prepared in lipid emulsion, package insert describes continuous infusion only (NO BOLUS)

Question 18

Phenylalkylamines

Answer 18

Verapamil
at doses that cause peripheral vasodilation, verapamil has greater direct negative chronotropic, dromotropic and inotropic effects than DHP
Negative chronotropic effect slows HR
Direct negative inotropic effect decreases contractility
Care must be used in patients with limited LV function

Question 19

Cautions with verapamil

Answer 19

patients taking Beta Blockers or digoxin

Question 20

Contraindications to Verapamil

Answer 20

WPW, sick sinus syndrome, AV block, HF

Question 21

Diarylaminoproplyamine esters

Answer 21

Bepridil
vascorindicated for angina pectoris
DOES NOT LOWER BP
lowers myocardial O2 demand
can cause significant brady and is reserved for patients who do not respond to other therapies (nitrates, CCB, Beta Blockers)

Question 22

Benzimidole-substitured tetralines

Answer 22

Mibefradil
potent peripheral and coronary vasodilator
in contrast, it has a negligible negative inotropic effect
reflec tachhycardia does not appear as with nifedipine
voluntarily withdrawn from the market

Question 23

Anesthetic implications of CCB

Answer 23

verapamil is used to terminate PAT or PSVT
Sublingual procardia (nifedipine) used to be used a a treatment for period HTN. No longer used because of serious side effects (cerebral/coronary ischemia, severe hypotension)
IV nicardipine for treatment of perioperative HTN 1amp in 100ml NS = 0.25mg/ml