How does Cardizem (Diltiazem) work?

From the Guidelines

Cardizem (diltiazem) works by reducing cell transmembrane inward calcium flux, which inhibits both myocardial and vascular smooth muscle contraction, and also slows AV conduction and depresses sinus node impulse formation. This medication prevents calcium from entering the cells of the heart and arterial walls, which slows electrical conduction in the heart, relaxes blood vessels, and reduces the heart's workload [ 1 ]. Specifically, Cardizem decreases the heart rate, slows electrical signals through the AV node, and dilates coronary and peripheral arteries. These actions make it effective for treating conditions like high blood pressure, angina (chest pain), and certain abnormal heart rhythms such as atrial fibrillation.

Key Mechanisms of Action

• Reduces myocardial oxygen demand by decreasing afterload, contractility, and heart rate
• Improves myocardial flow by dilating coronary arterial and arteriolar vessels
• Has beneficial effects on LV relaxation and arterial compliance

Clinical Use and Side Effects

Cardizem is typically prescribed at doses ranging from 120-540 mg daily, depending on the formulation (immediate or extended-release) and the condition being treated [ 1 ]. Side effects may include hypotension, worsening HF, bradycardia, and AV block. Patients should take Cardizem consistently and avoid stopping it suddenly as this could worsen their condition.

Important Considerations

• Verapamil and diltiazem should be avoided in patients with pulmonary edema or evidence of severe LV dysfunction [ 1 ]
• Amlodipine and felodipine are reasonably well tolerated by patients with mild LV dysfunction [ 1 ]

From the FDA Drug Label

The therapeutic benefits achieved with diltiazem hydrochloride are believed to be related to its ability to inhibit the influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle Although precise mechanisms of its antianginal actions are still being delineated, diltiazem hydrochloride is believed to act in the following ways: • Angina Due to Coronary Artery Spasm: Diltiazem hydrochloride has been shown to be a potent dilator of coronary arteries both epicardial and subendocardial • Exertional Angina: Diltiazem hydrochloride has been shown to produce increases in exercise tolerance, probably due to its ability to reduce myocardial oxygen demand. Diltiazem produces relaxation of coronary vascular smooth muscle and dilation of both large and small coronary arteries at drug levels which cause little or no negative inotropic effect

Diltiazem works by inhibiting the influx of calcium ions during membrane depolarization of cardiac and vascular smooth muscle. It acts as a potent dilator of coronary arteries, and produces increases in exercise tolerance by reducing myocardial oxygen demand. This is accomplished via reductions in heart rate and systemic blood pressure at submaximal and maximal exercise workloads 2.

• Main mechanisms of action include:
  • Inhibition of calcium ion influx
  • Dilation of coronary arteries
  • Reduction of myocardial oxygen demand
  • Decrease in heart rate and systemic blood pressure

From the Research

Mechanism of Action

• Cardizem, also known as diltiazem, is a calcium channel blocker that works by inhibiting the influx of calcium ions into cardiac and vascular smooth muscle cells 3, 4.
• This inhibition leads to a decrease in myocardial contractility and vasodilation, resulting in a reduction in blood pressure and an improvement in angina symptoms 5, 6.
• Diltiazem has a unique property of blocking T-type calcium channels, which sets it apart from other calcium channel blockers 3.

Hemodynamic Effects

• Diltiazem produces similar hemodynamic and electrophysiological effects to those of verapamil, but has less potency in inducing arterial dilatation and more of a tendency to slow the heart rate 4.
• The drug does not appear to cause significant increases in coronary blood flow or bring about improvement in ejectional and isovolumic indices of myocardial contraction, evidence of its intrinsic negative inotropic effect 4.
• Diltiazem can lower diastolic pressure in 40% to 80% of patients with essential hypertension and can prolong treadmill capacity and reduce frequency of angina in patients with stable effort angina 6.

Clinical Applications

• Diltiazem is used to treat hypertension and angina pectoris, and can be used in combination with other medications such as beta blockers and nitrates 5, 6, 7.
• The choice of diltiazem as a treatment option should be individualized, based upon accompanying illnesses, adverse-effect profile, and demographic factors 7.