CALCIUM CHANNEL BLOCKERS 

 1. BASIC PHYSIOLOGY & MECHANISM

Calcium channels in cardiovascular system

  • L-type Ca²⁺ channels → predominant in:
    • Cardiac myocytes
    • SA node & AV node
    • Vascular smooth muscle

 Function

  • Ca²⁺ influx →
    → myocardial contraction (inotropy)
    → nodal conduction (chronotropy, dromotropy)
    → vascular tone

 Mechanism of Action

CCBs block L-type Ca²⁺ channels → ↓ intracellular Ca²⁺

Effects:

Site

Effect

Heart

↓ contractility (negative inotropy)

SA node

↓ HR (negative chronotropy)

AV node

↓ conduction (negative dromotropy)

Vessels

Vasodilation (↓ SVR)

2. CLASSIFICATION 

 Non-Dihydropyridines (Cardioselective)

  • Verapamil
  • Diltiazem

 More effect on heart


 Dihydropyridines (Vasoselective)

  • Amlodipine
  • Nifedipine
  • Nicardipine
  • Clevidipine
  • Nimodipine

 More effect on vascular smooth muscle


 3. COMPARISON 

Feature

Non-DHP

DHP

HR

↓↓↓

↑ (reflex tachycardia)

Contractility

↓↓↓

Minimal

AV conduction

↓↓↓

No effect

Vasodilation

Moderate

Marked

ICU use

Arrhythmia control

Hypertensive emergencies

4. ICU INDICATIONS 

 A. Tachyarrhythmias

  • AF with RVR
  • SVT (rate control)

 Drug of choice:Diltiazem (preferred),Verapamil


 B. Hypertensive emergencies

  • Neurocritical care (ICH, SAH)
  • Aortic dissection (with β-blocker)
  • Postoperative hypertension

 Preferred IV agents:Nicardipine,Clevidipine


 C. Subarachnoid hemorrhage (SAH)

  • Prevent vasospasm

 DOC:Nimodipine

 Improves neurological outcome (NOT mortality)


 D. Coronary vasospasm (Prinzmetal angina)

  • DHP preferred

 E. Pulmonary hypertension (selected patients)

  • Only vasoreactive group

 F. NOT preferred in:

  • Cardiogenic shock
  • Severe LV dysfunction

 5. DOSING IN ICU 

 Diltiazem (AF with RVR)

  • Bolus: 0.25 mg/kg IV
  • Repeat: 0.35 mg/kg
  • Infusion: 5–15 mg/hr

 Verapamil

  • Bolus: 5–10 mg IV slow
     Higher risk of hypotension

Nicardipine

  • Start: 5 mg/hr IV
  • Titrate: +2.5 mg/hr every 5–15 min
  • Max: 15 mg/hr

 Clevidipine 

  • Start: 1–2 mg/hr
  • Rapid titration (every 90 sec)
  • Max: 16–32 mg/hr

 Lipid emulsion (like propofol)


 Nimodipine (SAH)

  • 60 mg PO/NG every 4 hours
     If hypotension → reduce dose


 6. ADVERSE EFFECTS 

 Cardiovascular

  • Hypotension
  • Bradycardia
  • AV block
  • Worsening heart failure

 Others

  • Peripheral edema
  • Constipation (verapamil)
  • Flushing, headache

 Severe toxicity

→ CCB overdose:

  • Shock
  • Bradycardia
  • Hyperglycemia (key differentiator from β-blocker toxicity)

 7. CCB TOXICITY 

Pathophysiology

  • ↓ insulin release → hyperglycemia
  • ↓ cardiac contractility
  • Vasodilation

 MANAGEMENT 

Stepwise approach:

  1. IV Calcium
    • Calcium gluconate / chloride
  1. High-dose insulin euglycemia therapy (HIET)
    • Improves myocardial metabolism
  1. Vasopressors-Noradrenaline,Adrenaline
  1. Lipid emulsion therapy
  2. Pacing (if bradycardia)
  3. ECMO (refractory shock)

 8. DRUG INTERACTIONS

 Dangerous combinations

  • CCB + β-blocker → severe bradycardia/heart block
  • With digoxin → ↑ digoxin levels
  • CYP3A4 inhibitors → ↑ toxicity

 9. SPECIAL ICU PEARLS

✔ Clevidipine preferred when:

  • Need rapid titration
  • Short half-life needed

✔ Nicardipine preferred in:

  • Neuro ICU (stable BP control)

✔ Diltiazem vs β-blocker:

  • Use Diltiazem if:
    • Asthma/COPD
    • β-blocker contraindicated

✔ Nimodipine:

  • Give even if normotensive SAH
  • Avoid IV (risk of collapse)