Calcium Channel Blockers

Muscle cells — in blood-vessel walls and in the heart — only contract when calcium rushes in through channels in their membrane. The relevant channel here is the L-type voltage-gated calcium channel. In vascular smooth muscle, calcium entry causes the vessel to squeeze (raising blood pressure). In the heart, calcium entry powers each contraction and, in the SA and AV nodes, sets the pace and speed of electrical conduction.

So calcium is the common trigger for two very different jobs: tightening arteries and driving the heartbeat. Block its entry and you can relax vessels, slow the heart, or both — depending on *which tissue* the drug prefers.

This is the single most important concept for the class. Dihydropyridines (the -dipine drugs: amlodipine, nifedipine) are vessel-selective — they relax arteries with little direct effect on the heart. Non-dihydropyridines (diltiazem and verapamil) are heart-selective — they act on the myocardium and the SA/AV nodes, slowing rate and conduction.

Get this split right and the entire drug behaves predictably: -dipines lower BP and can cause reflex tachycardia and ankle edema; diltiazem/verapamil slow the heart and can cause bradycardia, AV block, and constipation.

With -dipines, arteries dilate faster than the heart can adjust, so the body may respond with a reflex tachycardia, and pooling of fluid in dilated capillaries produces ankle edema (which does *not* respond to diuretics because it isn’t fluid overload).

With diltiazem/verapamil, the danger is the opposite — the heart can be slowed too much, causing bradycardia or AV block, and their negative effect on contractility can worsen a failing heart. Combining them with a beta-blocker is especially risky because both slow the AV node — the effects add up and can stop conduction.