Is diltiazem (calcium channel blocker) a smooth muscle relaxant?

Diltiazem as a Smooth Muscle Relaxant

Yes, diltiazem is a smooth muscle relaxant that works by inhibiting calcium influx during membrane depolarization of vascular smooth muscle, causing relaxation and vasodilation. 1

Mechanism of Action

Diltiazem, a non-dihydropyridine calcium channel blocker, acts through the following mechanisms:

• Inhibits voltage-dependent L-type calcium channels in cell membranes, preventing calcium influx during membrane depolarization 2
• Causes excitation-contraction uncoupling in various myocardial and vascular smooth muscle tissues 1
• Produces relaxation of coronary vascular smooth muscle and dilation of both large and small coronary arteries 1
• Decreases peripheral vascular resistance, leading to vasodilation and reduced blood pressure 1

Effects on Different Smooth Muscle Types

Vascular Smooth Muscle

• Diltiazem produces relaxation of coronary vascular smooth muscle at drug levels that cause little or no negative inotropic effect 1
• Results in dose-dependent decreases in systemic blood pressure and peripheral resistance 1
• Causes a decrease in peripheral vascular resistance and a modest fall in blood pressure 1

Gastrointestinal Smooth Muscle

• Decreases smooth muscle contraction in the gastrointestinal tract 3
• Reduces amplitude of peristalsis and decreases lower esophageal sphincter pressures 3
• Has been studied for potential therapeutic use in diffuse esophageal spasm and other gastrointestinal disorders involving smooth muscle hypercontractility 4, 3

Pharmacological Classification

Diltiazem belongs to the non-dihydropyridine class of calcium channel blockers, which are:

• Less selective for vasculature than dihydropyridines (like amlodipine, nifedipine) 2
• Have stronger effects on cardiac conduction than dihydropyridines 2
• Cause moderate vasodilation compared to the potent peripheral vasodilation seen with dihydropyridines 2

Clinical Applications Related to Smooth Muscle Effects

Diltiazem's smooth muscle relaxant properties contribute to its therapeutic uses in:

1. Coronary Artery Spasm: Acts as a potent dilator of coronary arteries, inhibiting both spontaneous and ergonovine-induced coronary artery spasms 1

2. Hypertension: Reduces peripheral vascular resistance through smooth muscle relaxation, leading to decreased blood pressure 1, 5

3. Angina: Improves exercise tolerance by reducing myocardial oxygen demand through reductions in heart rate and systemic blood pressure 1

4. Supraventricular Tachycardia: Used intravenously for management of SVT, as noted in clinical guidelines 6

5. Gastrointestinal Disorders: Has been investigated for conditions involving excessive smooth muscle contraction, such as diffuse esophageal spasm 4, 3

Experimental Evidence

Early research demonstrated diltiazem's direct effects on vascular smooth muscle:

• In rabbit pulmonary and mesenteric arteries, diltiazem (1-10 μg/ml) suppressed mechanical responses of smooth muscle 7
• Raised the critical membrane potential required to evoke contraction 7
• Reduced the amplitude of contraction at any given depolarization level 7

Clinical Considerations

When using diltiazem for its smooth muscle relaxant properties, be aware of:

• Common side effects: Headache, flushing, peripheral edema, and hypotension 5
• Serious adverse events: Atrioventricular block (rare but important, especially in elderly patients) 5
• Contraindications: Should be avoided in patients with AV block greater than first degree, SA node dysfunction, hypotension, decompensated systolic heart failure, or significant left ventricular dysfunction 6, 2
• Drug interactions: Caution with other drugs that have SA or AV nodal-blocking properties 6

Diltiazem's smooth muscle relaxant properties make it valuable for treating various cardiovascular conditions, with potential applications in other systems where smooth muscle hypercontractility contributes to pathology.