Diltiazem serves as both a blood pressure-lowering medication and an antiarrhythmic agent. This pharmaceutical compound operates by inhibiting the influx of calcium ions through the slow, voltage-dependent L-type calcium channels in the smooth muscle and cardiac muscle cells. This mechanism results in decreased contractility of these muscle cells, leading to vasodilation, reduction in afterload, and a consequent decrease in blood pressure. Additionally, Diltiazem exhibits a negative chronotropic effect, which mitigates the reflex increase in heart rate.

Furthermore, Diltiazem is classified as a Class IV antiarrhythmic drug due to its ability to delay atrioventricular conduction. Unlike dihydropyridine calcium channel blockers, Diltiazem also demonstrates a negative inotropic effect.

Indications for Use

Diltiazem is approved for treating symptomatic coronary artery disease, including various forms of angina pectoris, as well as hypertension. Typically, extended-release oral formulations are preferred for administration. Off-label, Diltiazem is utilized in topical preparations for treating anal fissures, primarily to alleviate the underlying hypertonicity of the anal sphincter.

Dosage Recommendations

The standard recommended dosage of Diltiazem is 180 mg per day, which can be divided into one or two doses when using extended-release forms, or into three doses for immediate-release forms. If the therapeutic effect is inadequate, the daily dose may be increased to a maximum of 360 mg. Regular assessments should be conducted during long-term treatment to determine if dosage reductions are possible. Caution is advised for patients with liver and/or kidney dysfunction, as well as for the elderly. The medication should be taken whole, preferably after meals, with adequate fluids.

Potential Side Effects

Common side effects associated with Diltiazem include peripheral edema, headaches, dizziness, fatigue, a sense of weakness, AV block, palpitations, flushing, gastrointestinal disturbances such as constipation and nausea, as well as skin reactions. The medication may impair the ability to participate in activities requiring alertness, particularly during the initial stages of treatment, after dose adjustments, or when switching formulations.

Drug Interactions

Diltiazem is metabolized via the CYP3A4 enzyme and functions as an inhibitor of this enzyme. Caution is warranted when Diltiazem is co-administered with other substrates of CYP3A4, such as Simvastatin, Lovastatin, Atorvastatin, Carbamazepin, Midazolam, Triazolam, Alfentanil, Theophyllin, Ciclosporin A, and cardiac glycosides, as it may necessitate dose adjustments. Concurrent use with Rifampicin, Cimetidine, or Ranitidine can alter Diltiazem plasma levels, warranting careful monitoring of patients. When combined with other antihypertensive agents, the blood pressure-lowering effects can be additive, increasing the risk of hypotension. The vasodilatory effects of nitrates can also be enhanced by Diltiazem. Additionally, the cardiac effects of various anesthetics may be intensified, necessitating disclosure of Diltiazem use to the anesthesiologist prior to general anesthesia.

Contraindications

Certain medications are contraindicated during Diltiazem therapy, including Ivabradine, Lomitapid, and intravenous Dantrolene. The intravenous administration of beta-blockers is also inadvisable. Other contraindications encompass second- or third-degree AV block, acute myocardial infarction, manifest heart failure, atrial fibrillation or flutter, and a resting heart rate below 50 beats per minute.

Use in Pregnancy and Lactation

Pregnancy is a contraindication for the use of Diltiazem, and it is advised that breastfeeding should cease if Diltiazem treatment becomes necessary. However, the Embryotox center at the Berlin Charité states that continuing a previously initiated Diltiazem therapy during pregnancy may be acceptable if better-studied antihypertensive alternatives are not viable. Similar recommendations apply to lactation, where alternatives are preferred due to limited experience with Diltiazem.

Classification of Calcium Channel Blockers

Calcium channel blockers represent a diverse class of medications. They can be categorized into dihydropyridine (DHP), phenylalkylamine, and benzothiazepine derivatives. DHP derivatives typically end in -dipine, with Nifedipine being a prototype followed by advanced formulations such as Felodipine and Amlodipine. These compounds primarily induce vasodilation in the arterial system. Diltiazem, as the sole benzothiazepine representative, alongside phenylalkylamine derivatives like Verapamil, exerts direct cardiac effects, including reductions in heart rate, AV conduction, and contractility. Variations in their pharmacological profiles are likely due to differences in their binding sites on calcium channels or variations in the structural composition of channel proteins in myocardial versus smooth muscle tissue.