Calcium Channel Blockers

Mechanism of Action

  • Promote vasodilator activity (reducing blood pressure) by reducing calcium influx into vascular smooth muscle cells by interfering with voltage operated calcium channels (and to a lesser extent receptor-operated channels) in the cell membrane.
  • This also has an extra effect on cardiac myocytes- causing negative inotropy (decreased cardiac output) and, to a certain extent, negative chronotropy and dromotropy (slowing of cardiac conduction), depending on the CCB.

Classes of CCBs

  • Dihydropyridine derivatives (namely amlodipine)
    • Pronounced vasodilator properties; intense reflex cardiac stimulation usually overcomes any direct cardiac effects
  • Rate-limiting CCBs (usually verapamil or diltiazem)
    • More noticeable cardiac effects

Indications

  • Stable angina where beta-blockers are contraindicated (rate limiting CCB- diltiazem)
  • Hypertension in older people (dihydropyridine class- amlodipine)
    • NB Dihydropyridines can also be used in angina
  • May also be used in the symptomatic treatment of Reynaud’s
  • Occasionally used for management of AF (again, where beta-blocker is contraindicated; verapamil is commonly used)
    • NB the BNF says that verapamil is contraindicated where an accessory pathway is involved (risk of acceleration).  However, they remain in use as antiarrhythmic drugs for SVTs (often second or third line)
  • Special CCBs can be used under certain circumstances e.g. nimodipine for prevention/treatment of vascular spasm after subarachnoid haemorrhage

Contraindications

  • Rate-limiting CCBs should be avoided in heart failure (may worsen symptoms/ cause deterioration)
  • Rate-limiting CCB should be avoided with concomitant beta blocker use or in severe bradycardia; 2nd/3rd degree heart block; sick sinus syndrome;
    • Also avoid in the acute phase of an MI (bradycardia; hypotension; LVF)
  • Cardiogenic shock, unstable angina and significant aortic stenosis
    • Hypotension is a relative contraindication

Cautions

  • Hepatic impairment- may need to reduce dose; renal impairment- consider starting at a lower dose
  • It is not recommended to stop CCBs suddenly (risk of rebound tachycardia)

Side effects

  • Common
    • Abdominal pain; nausea; constipation (particularly verapamil)
    • Palpitations (reflex response for dihyrdopyridines); flushing; oedema (NB diuretics are often not helpful, but ACEIs/ARBs may be helpful)
      • RLCCBs also can cause bradycardia; SA block/AV block;
    • Headache; dizziness; sleep disturbance; fatigue/malaise; hypotension
  • Less commonly
    • GI disturbance (usually constipation due to effect on GI CC receptors); weight change
    • Dry mouth; taste disturbance
    • Hypotension; syncope; chest pain; dyspnoea;
    • Rhinitis
    • Mood changes
    • Muscle weakness; tremor; paraesthesia; myalgia; muscle cramps; back pain; arthralgia
    • Urinary disturbance; impotence; gynaecomastia
    • Visual disturbance; tinnitus
    • Rash (including erythema multiforme); pruritus; sweating; alopecia; purpura; skin discolouration
  • Very rarely
    • Gastritis; pancreatitis; hepatitis; jaundica; cholestasis; gingival hyperplasia (particularly for rapid onset/short acting)
    • Myocardial infarction; arrhythmias; tachycardia; vasculitis;
    • Coughing
    • Peripheral neuropathy; hyperglycaemia
    • Thrombocytopenia;
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