Diltiazem: Mechanism, Uses, and Pharmacokinetics

• Diltiazem is a benzothiazepine calcium channel blocker medication
• Used to treat hypertension, angina pectoris, and some types of arrhythmia

Mechanism of Action

• Blocks calcium channels in cardiac and vascular smooth muscle
• Reduces intracellular calcium
• Decreased calcium influx causes relaxation of vascular smooth muscle, leading to vasodilation and reduced blood pressure
• Decreases heart rate through slowed SA node automaticity
• Slows AV node conduction
• Decreases myocardial contractility

Pharmacokinetics

• Administered orally and intravenously
• Rapid oral absorption, limited bioavailability due to first-pass metabolism
• Metabolized in the liver by cytochrome P450 enzymes
• Metabolites are excreted in urine and feces
• Half-life is approximately 3-9 hours, which can be prolonged with chronic use or in patients with liver impairment

Indications

• Effective for lowering blood pressure by vasodilation for hypertension
• Reduces frequency and severity of angina attacks by decreasing myocardial oxygen demand for angina pectoris
• Controls heart rate in SVT by slowing AV node conduction
• Slows ventricular response in atrial fibrillation and atrial flutter

Dosage and Administration

• Dosage varies based on indication and individual factors
• For hypertension:
  • Start with 60-120 mg twice daily for sustained-release formulations
  • Adjust dosage based on blood pressure response
• For angina:
  • Start with 30 mg four times daily or 60 mg three times daily for immediate-release formulations
  • Sustained-release formulations are available
• For SVT:
  • Administer an IV bolus of 0.25 mg/kg over 2 minutes, followed by continuous infusion
  • Initiate oral maintenance therapy after acute control
• Available in immediate-release tablets, extended-release capsules, and intravenous solutions

Contraindications

• Hypersensitivity to diltiazem or its components
• Sick sinus syndrome or AV block (without a functioning pacemaker)
• Hypotension (systolic blood pressure < 90 mmHg)
• Acute myocardial infarction with pulmonary congestion
• Concurrent use with intravenous beta-blockers

Adverse Effects

• Common side effects:
  • Headache
  • Dizziness
  • Bradycardia
  • Hypotension
  • Peripheral edema
  • Constipation
• Less common but serious adverse effects:
  • AV block
  • Congestive heart failure
  • Liver enzyme elevations
  • Allergic reactions

Drug Interactions

• With Beta-Blockers: May cause excessive bradycardia, hypotension, and heart failure
• With Digoxin: Can increase digoxin levels, potentially leading to toxicity
• With Antiarrhythmics: Increased risk of arrhythmias
• With Statins: Can increase statin levels, raising the risk of myopathy
• With Immunosuppressants: Can increase levels of cyclosporine and tacrolimus
• CYP3A4 Inhibitors/Inducers: Affect diltiazem metabolism and levels
• Grapefruit juice may increase diltiazem levels

Special Populations

• Use during pregnancy only if the potential benefit justifies the risk to the fetus
• Diltiazem is excreted in breast milk; caution is advised during breastfeeding
• Elderly patients may be more sensitive to hypotensive effects
• Dose adjustments may be necessary for renal impairment
• Dose adjustments are necessary for hepatic impairment due to reduced metabolism

Monitoring

• Monitor blood pressure and heart rate regularly, especially during initial therapy and dose adjustments
• Monitor ECG in patients with arrhythmias or those at risk of AV block
• Monitor liver function tests periodically, especially in patients with liver disease or those taking other hepatotoxic drugs
• When used concurrently with digoxin, monitor digoxin levels
• Assess renal function periodically, especially in patients with renal impairment

Overdosage

• Symptoms:
  • Hypotension
  • Bradycardia
  • AV block
  • Heart failure
• Treatment includes:
  • Supportive care, including IV fluids and vasopressors for hypotension
  • Atropine for bradycardia
  • Calcium gluconate to reverse calcium channel blockade
  • Cardiac pacing for severe AV block

Explore diltiazem, a benzothiazepine calcium channel blocker used for hypertension, angina, and arrhythmias. Learn about its mechanism of action, which involves blocking calcium channels to relax vascular smooth muscle and reduce heart rate. Understand its pharmacokinetics, including oral and intravenous administration.