Calcium Channel Blockers Flashcards
role of calcium in cardiac and smooth muscle
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.
Six tyoes of Calcium channels
L,N,P,Q,R,T
L type channels
sustained conductance, slow inactivation
T type channels
similr to L but rapid inactivation, minimal sensitivity to CCB
5 subunits of L type channels
Alpha 1, alpha 2, beta, gamma, and delta
how do phenylalkylamines work?
verapamil
bind to intracellular portion of alpha 1 subunit
how do benzothiazepines work?
diltiazem
mechanism not well understood
how do 1,4-dihydropyridines work?
modulate the L-type channel, vascular smooth muscle
what are the 5 major classes of CCB?
benzothiazeprines: Diltizem
DHP: Nicardipine, nifedipine, nimodipine, clevidipine, amlodipine
Phenylalkylamines: Verapamil
Diarylaminopropylamine ethers: bepridil
Benzimidazole- substituted tetralines: mibefradil
Pharm of Non-dihydropyridines
negative inotropic effect
negative chronotropic effect
negative dromotropic effect
positive lusitropic effect
Pharmacology of ALL CCB
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
common indications for CCB
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
Common side effects
orthostatic hypotension, bradycardia, peripheral edema, dizziness, headaches, flushing, N/V
cautions with CCB
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
DHP
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
Nicardipine
DHP, commonly used in OR, can be given IV bolus or continuous
Clevidipine
DHP, very fast onset and offset, faster than nicardipine, prepared in lipid emulsion, package insert describes continuous infusion only (NO BOLUS)
Phenylalkylamines
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
Cautions with verapamil
patients taking Beta Blockers or digoxin
Contraindications to Verapamil
WPW, sick sinus syndrome, AV block, HF
Diarylaminoproplyamine esters
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)
Benzimidole-substitured tetralines
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
Anesthetic implications of CCB
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
