Monday, June 3, 2013

Calcium Channel Blockers and Beta-Blockers

If a patient presents in rapid Afib and is currently taking a beta-blocker, should a beta-blocker be used for rate control? Conversely, if a similar patient presents, but is taking a calcium channel blocker, should a ccb be used for rate control? 

I was asked this question years ago.  Essentially, the concern was that if a ccb and a beta-blocker were combined, additive (if not synergistic) cardiac depression would occur. The specific concern was a “sequential AV nodal block.” Whatever that meant, I searched for this answer, and the best I could come up with relies entirely on pharmacology.

Calcium channel blockers (L-type) prevent calcium influx into myocardial cells.  Less calcium entry into cells reduces the magnitude of calcium dependent calcium release from the sarcoplasmic reticulum.   Muscle contractions are then diminished from a lack of calcium available to bind to troponin c, which would normally allow actin and myosin to bind. In cardiac conduction, calcium channel antagonism decelerates the recovery of the slow calcium channels in the SA and AV nodal tissue resulting in a decreased heart rate and conduction.

Beta-blockers slow the rate of pacemaker cell depolarization, decrease spontaneous firing rate of sinus or ectopic pacemakers, and slow conduction through atrial and AV nodal tissue. After antagonism of g-protein coupled adrenergic receptors, decreased activation of adenylyl cyclase and decreased formation of cAMP lead to inhibition of phosphorylation of several intracellular processes. Interestingly, many of these effects lead to either decreased calcium flux and effects on the SR similar to CCBs, but through different mechanisms

From a pharmacological point of view, risk of additive effects exists that could potentiate significant cardiac effects.  Absent clinical data or case reports of such events suggests that although a theoretical risk exists, the clinical effects of this interaction may not be significant.

Goldfrank’s Toxicologic Emergencies
Goodman & Gillman Pharmacologic Basis of Therapeutics

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