Calcium Channel Blockers Mechanism of Action

Calcium Channel Blockers

Mechanism of Action

• Calcium channel blockers (CCBs) work by blocking the influx of calcium ions into vascular smooth muscle cells and cardiac cells
• This leads to:
  • Relaxation of vascular smooth muscle, causing vasodilation
  • Decreased peripheral resistance
  • Decreased blood pressure
• CCBs also:
  • Inhibit the contraction of cardiac muscle, reducing cardiac output
  • Decrease the frequency of the heart's contractions
• The combined effect is a decrease in blood pressure and a reduction in the workload on the heart

Adverse Effects

• Common adverse effects:
  • Dizziness or lightheadedness due to vasodilation
  • Headache
  • Flushing
  • Peripheral edema (swelling of the legs and ankles)
• Less common adverse effects:
  • Bradycardia (slow heart rate)
  • Hypotension (low blood pressure)
  • Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Rare but serious adverse effects:
  • Angioedema (severe allergic reaction)
  • Stevens-Johnson syndrome (severe skin and mucous membrane disorder)
  • Heart block (impaired heart rhythm)

Calcium Channel Blockers

Mechanism of Action

• Block influx of calcium ions into vascular smooth muscle cells and cardiac cells
• Result in relaxation of vascular smooth muscle, causing vasodilation
• Decrease peripheral resistance
• Decrease blood pressure
• Inhibit contraction of cardiac muscle, reducing cardiac output
• Decrease frequency of heart's contractions
• Combined effect: decrease in blood pressure and reduction in heart's workload

Adverse Effects

• Common:
  • Dizziness or lightheadedness due to vasodilation
  • Headache
  • Flushing
  • Peripheral edema
• Less common:
  • Bradycardia
  • Hypotension
  • Gastrointestinal disturbances
• Rare but serious:
  • Angioedema
  • Stevens-Johnson syndrome
  • Heart block

Calcium Channel Blockers (CCBs)

Mechanism of Action

• Inhibit influx of calcium ions into vascular smooth muscle cells and cardiac myocytes to reduce muscle contraction and vasodilation
• Block L-type calcium channels to decrease contraction force of the heart and lower blood pressure

Adverse Effects

• Common: headache, dizziness, flushing, peripheral edema
• Less common: bradycardia, AV block, hypotension, constipation
• Rare: allergic reactions, Stevens-Johnson syndrome, lupus-like syndrome

Classes of CCBs

Dihydropyridines (DHPs)

• Most commonly used CCBs
• Examples: nifedipine, amlodipine, felodipine

Phenylalkylamines

• Less commonly used CCBs
• Examples: verapamil, gallopamil

Benzothiazepines

• Less commonly used CCBs
• Examples: diltiazem, clentiazem

Therapeutic Indications

• Hypertension (primary indication)
• Angina pectoris
• Supraventricular tachyarrhythmias (PSVT, atrial fibrillation)
• Raynaud's phenomenon
• Migraine prophylaxis

Pharmacokinetics

• Well absorbed from the GI tract, with varying bioavailability among CCBs
• High protein binding (90-98%)
• Metabolized by the liver via CYP3A4
• Elimination half-life: 2-12 hours, depending on the CCB