Verapamil

Pharmacokinetics of the drug

Upon oral administration, the drug demonstrates an excellent absorption capacity—up to 90% of the administered dose is absorbed in the gastrointestinal tract. However, despite such high absorption rates, the final bioavailability of the drug remains paradoxically low, varying within 20–35%. The main reason for this phenomenon lies in pronounced presystemic elimination. This means that during the initial blood flow passage from the intestines through the liver (first-pass effect), the major portion of the active substance undergoes metabolism and is degraded before reaching the systemic circulation and target organs.

The temporal parameters of the drug's action are clearly defined. Following oral administration, the onset of the therapeutic effect is observed in approximately 1 hour. The drug reaches its peak—maximum concentration and intensity of action—in 2 hours. The standard duration of the antianginal effect ranges from 8 to 10 hours. For patient convenience, prolonged-release dosage forms exist that can maintain the required blood concentration for up to 24 hours. The half-life ($t_{1/2}$) ranges from 3 to 7 hours. The elimination of metabolites occurs predominantly via urine and bile, while an extremely small fraction—only 3–4%—is excreted unchanged.

Mechanism of antianginal action

The mechanism of the drug's antianginal action is complex and based on the ability to block slow calcium channels. This process can be divided into three key components that collectively restore the balance between myocardial oxygen demand and supply.

1. Cardiac effect (reduction in $O_2$ demand). The drug directly affects the heart by blocking calcium channels in cardiomyocyte membranes. The decrease in intracellular calcium ion concentration leads to a predictable reduction in myocardial contractility and heart rate. As a result, the overall mechanical work of the heart decreases, which is critical for lowering myocardial oxygen demand under ischemic conditions.
2. Peripheral vascular effect (reduction in $O_2$ demand). The second site of action is the smooth muscle of resistance blood vessels. Calcium channel blockade in this area causes relaxation of the muscular wall and pronounced vasodilation. Expansion of the vascular bed leads to a drop in total peripheral vascular resistance (TPVR). Consequently, the heart requires less effort to eject blood into the aorta—afterload is reduced, which further conserves oxygen.
3. Coronary effect (increase in $O_2$ delivery). The drug directly affects the calcium channels of the coronary vessels supplying the heart itself. Their dilation leads to improved myocardial blood supply, thereby increasing the volume of oxygen delivered to areas suffering from hypoxia.

Indications and side effects

Based on the described pharmacodynamic effects, the drug has found wide application in clinical practice.

Main indications for prescription:

• Effort angina — for the prevention of retrosternal pain attacks triggered by physical or emotional stress.
• Vasospastic angina — due to the drug's ability to relieve coronary artery spasm.
• Supraventricular arrhythmias — in this situation, the drug is used as an effective Class IV antiarrhythmic agent.

Side effects: Despite its high efficacy, therapy requires monitoring due to potential adverse reactions. The most significant of these are cardiac complications. Depression of the conduction system can provoke the development of atrioventricular (AV) block. Excessive bradycardia (marked slowing of the pulse) and hypotension (decrease in blood pressure) may also occur. Among extracardiac side effects, patients most frequently note dyspeptic disorders such as nausea and vomiting.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Presystemic elimination and the hepatic first-pass effect.
• The role of calcium channels in cardiomyocyte and smooth muscle contraction.
• Mechanisms regulating total peripheral vascular resistance (TPVR).
• Pathogenesis of atrioventricular block development during drug therapy.
• Pharmacokinetic features of prolonged-release dosage forms.

Other topics in the section "Cardiovascular Drugs"

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