Verapamil

BRAND NAMES

Calan SR: It contains Verapamil as a main ingredient. It is available in film coated sustained release tablets.

MECHANISM OF ACTION

Verapamil is a non-dihydropyridine calcium channel blocker. Calcium channel blockers restrict calcium ions from entering the slow L-type calcium channels in the heart and vascular smooth muscle during depolarisation. This inhibition relaxes the coronary vascular smooth muscle while promoting coronary vasodilation, which is favourable to hypertension patients. Verapamil also enhances myocardial oxygen transport, which helps those with vasospastic angina. Verapamil is related with negative chronotropic effects and decreased sympathetic nervous system activity.

PHARMACODYNAMICS

Absorption

More than 90% of verapamil is absorbed when taken orally, but due to the high first-pass metabolism, bioavailability is substantially lower (10-35%).

Distribution

Verapamil's steady-state volume of distribution is around 300L for the R-enantiomer and 500L for the S-enantiomer.Verapamil is highly protein-bound in plasma. R-verapamil is 94% bound to serum albumin, whereas S-verapamil is 88% bound. Additionally, R-verapamil is 92% attached to alpha-1 acid glycoprotein, whereas S-verapamil is 86% bound.

Metabolism

Verapamil is extensively metabolised by the liver, with up to 80% of a given dosage eliminated by pre-systemic metabolism. Interestingly, this first-pass metabolism seems to remove the S-enantiomer of verapamil significantly quicker than the R-enantiomer. The remaining parent drug is O-demethylated, N-dealkylated, and N-demethylated to produce a variety of metabolites using the cytochrome P450 enzyme system. Norverapamil, a significant circulating metabolite, is the consequence of verapamil's N-demethylation via CYP2C8, CYP3A4, and CYP3A5, and contains roughly 20% of the parent drug's cardiovascular action.Verapamil metabolism also involves N-dealkylation via CYP2C8, CYP3A4, and CYP1A2 to the D-617 metabolite. Other CYP isoenzymes metabolise norverapamil and D-617 into a number of secondary metabolites. CYP2D6 and CYP2E1 are also involved in verapamil metabolism, but to a lower level. Minor pathways of verapamil metabolism include O-demethylation to D-703 via CYP2C8, CYP2C9, and CYP2C18, as well as D-702 via CYP2C9 and CYP2C18.

Elimination

Within 5 days, approximately 70% of the given dosage is eliminated as metabolites in urine and less than16% in faeces. Approximately 3% to 4% of the medication is eliminated unaltered in the urine.

PHARMACODYNAMICS

Verapamil is an L-type calcium channel blocker that has antiarrhythmic, antianginal, and antihypertensive properties. Immediate-release verapamil has a very limited duration of action, necessitating medication 3 to 4 times per day, while extended-release versions are available that allow for once-daily administration. Verapamil, a negative inotropic drug, should not be taken in individuals with severe left ventricular failure or hypertrophic cardiomyopathy because the reduction in contractility induced by verapamil may worsen these pre-existing problems.

DOSAGE AND ADMINISTRATION

Verapamil can be given orally (sustained or immediate release) or intravenously. It is feasible to open sustained-release verapamil capsules and sprinkle the contents over one spoonful of applesauce. Patients should be instructed to consume promptly with a full glass of cold water. Sustained verapamil products should be taken with meals and swallowed whole. When administered intravenously, verapamil must be given over at least two minutes.

Dosage for hypertension

• The normal dosing range for immediate-release formulations is 120 to 360 mg/day in three split doses, with a maximum dose of 480 mg/day.
• Consider lower beginning dosages for geriatric individuals and titrate based on response.
• The first dose of immediate-release oral formulations is 40 mg three times day.
• For extended-release oral formulations, start with a dosage of 120 mg once day in the morning or 100 mg once daily at evening.

Dosage for Angina

For oral administration, verapamil (immediate-release) should be given 80 mg to 160 mg three times per day.

CONTRAINDICATIONS

• Significant left ventricular dysfunction if the patient is hypersensitive to verapamil or any ingredient in the formulation (immediate-release or extended-release). 
• Severe hypotension is characterized by a systolic blood pressure measurement of less than 90 mmHg or, in the absence of a functioning mechanical ventricular pacemaker, cardiogenic shock. 
• A working artificial ventricular pacemaker is the lone exception to the sick sinus syndrome with second or third-degree atrioventricular block.
• Severe heart failure, unless it is caused by a verapamil-responsive supraventricular tachycardia.
• Concurrent use of beta-blockers intravenously.

DRUG INTERACTIONS

Verapamil may interact with the following products

• aliskiren,
• clonidine
• disopyramide
• dofetilide
• fingolimod
• labetalol
• lithium

Other drugs may interfere with verapamil's elimination from your body, affecting how it functions. Examples include erythromycin, rifamycins (including rifampin), and ritonavir.

SIDE EFFECTS

The common side effects of verapamil include

• Gingival hyperplasia
• Hypotension
• Peripheral edema
• Fatigue
• Constipation
• Dyspepsia

TOXICITY

An overdose of verapamil, like any other calcium channel blocker, can cause negative inotropic and chronotropic effects, dilatation of the arterial vasculature, and hypotension. Additionally, verapamil's blockage of slow calcium channels in pancreatic beta cells might impede insulin release, resulting in hyperglycemia. Verapamil toxicity is indicated when a patient develops bradycardia, hypotension/metabolic acidosis, and hyperglycaemic episodes. The most dangerous effects of a verapamil overdose are bradycardia and hypotension, which can potentially result in death if left untreated.

If a patient develops verapamil toxicity within one hour, two decontamination options exist: stomach lavage and single-dose activated charcoal. If a patient develops verapamil toxicity after 1 hour of consumption, total bowel irrigation with a polyethylene glycol electrolyte solution is an effective decontamination technique.