What are the dihydropyridine calcium channel blockers, such as amlodipine (Norvasc), nifedipine, felodipine, and nicardipine?

Dihydropyridine Calcium Channel Blockers

Dihydropyridine calcium channel blockers (DHPs) are a class of medications that selectively block L-type calcium channels in vascular smooth muscle, causing arterial vasodilation with minimal effects on cardiac conduction or contractility.

Mechanism of Action

Dihydropyridine CCBs work by:

• Inhibiting transmembrane calcium influx into vascular smooth muscle and cardiac muscle 1
• Selectively affecting vascular smooth muscle more than cardiac muscle 1
• Acting as peripheral arterial vasodilators that directly reduce peripheral vascular resistance 1
• Causing coronary vasodilation, which helps relieve angina symptoms 2

Types of Dihydropyridine CCBs

The major dihydropyridine calcium channel blockers include:

1. Amlodipine (Norvasc)

   • Long-acting (24-hour duration)
   • Once-daily dosing
   • Lower incidence of reflex tachycardia compared to short-acting agents 3
   • Reasonably well tolerated in patients with mild LV dysfunction 2

2. Nifedipine

   • Available in immediate-release and extended-release formulations
   • Immediate-release nifedipine is not recommended for unstable angina/NSTEMI except with concomitant beta-blockade due to increased risk 2
   • Ranks highest among DHPs for inducing peripheral edema 4

3. Felodipine

   • Highly vascular selective 5
   • Once-daily dosing with extended-release formulation
   • Well tolerated in mild LV dysfunction 2

4. Nicardipine

   • Short to medium duration of action
   • Requires multiple daily dosing 2

5. Other DHPs (mentioned in guidelines):

   • Isradipine
   • Nisoldipine
   • Nitrendipine
   • Lacidipine (not available in US, associated with lower rates of peripheral edema) 4, 6

Pharmacological Properties

DHPs share these key characteristics:

• High selectivity for vascular L-type calcium channels 2
• Pronounced peripheral arterial vasodilation 2
• Minimal effects on cardiac conduction (unlike non-dihydropyridine CCBs) 2
• Minimal direct effects on heart rate or AV conduction 2
• May cause reflex tachycardia, especially with short-acting formulations 2

Clinical Uses

Dihydropyridine CCBs are indicated for:

1. Hypertension - effective first-line agents 7
2. Chronic stable angina 2
3. Vasospastic (Prinzmetal's) angina - particularly effective 2
4. Unstable angina/NSTEMI - as add-on therapy when nitrates and beta-blockers are insufficient or contraindicated 2

Side Effects

Common adverse effects include:

• Peripheral edema (especially of lower extremities) - most common side effect 4
  • Nifedipine has highest risk of edema
  • Lacidipine has lowest risk of edema 4
  • Combining with ACE inhibitors or ARBs can reduce edema risk 4
• Headache
• Dizziness
• Flushing
• Palpitations 2

Important Clinical Considerations

1. Contraindications/Cautions:

   • Avoid immediate-release nifedipine without beta-blockade due to increased adverse events 2
   • Use with caution in heart failure patients 2

2. Differences from non-dihydropyridine CCBs (verapamil, diltiazem):

   • DHPs have more pronounced peripheral vasodilation 2
   • DHPs have minimal effects on cardiac conduction 2
   • Non-DHPs have significant effects on AV conduction and sinus node function 2

3. Managing DHP-induced edema:

   • Consider switching to a non-dihydropyridine CCB 8
   • Reduce dose of the DHP 8
   • Add complementary antihypertensive agents (ACEIs, ARBs, beta-blockers) to allow for DHP dose reduction 8

4. Generational differences:

   • Newer generation DHPs (amlodipine, felodipine) generally have longer half-lives and better tolerability profiles than first-generation agents like immediate-release nifedipine 3

DHPs are valuable agents for managing hypertension and angina, with their selective vascular effects making them particularly useful when cardiac conduction effects are undesirable. Their efficacy must be balanced against their tendency to cause peripheral edema, which varies among different agents within the class.