see also:

• calcium channels
• calcium channel blocker overdose
• historical perspective of calcium channel physiology and pharmacology
• cardiology
• pharmacology main index
• anti-arrhythmic agents

• act via specific membrane sites;

• marked suppression of SA automaticity & conduction;
• moderate coronary vasodilatation & -ve inotropy;
  • thus the reflex tachycardia due to decreased total peripheral resistance is blunted;
• may increase LV performance if no CCF but if CCF,
• marked decrease in contractility & LV function may occur.
• verapamil (Isoptin): (Isoptin, Veracaps SR)

• marked suppression of SA automaticity;
• moderate suppression of SA conduction;
• moderate coronary vasodilatation;
• mild -ve inotropy;
• diltiazem: (Cardizem)
  • ie. similar effects to verapamil;

• mibefradil: [Posicor]
  • less -ve inotropy?
  • still suppress AV node

• bind to the large alpha1 subunit & also inhibits Pdiesterase;
• marked coronary vasodilatation & arteriolar vasodilatation:
  • → decreases BP → increases symp.N.S. → increases HR, increases contractility & increases cardiac output;
• minimal -ve inotropy, & suppression of SA automaticity/cond.
• contra-indications:
  • unstable angina
  • uncontrolled congestive cardiac failure
  • immediately post-AMI
  • LV outflow obstruction
  • pregnancy
  • severe liver or renal impairment
  • strong inhibitors of the liver enzyme CYP3A4
  • use with cyclosporin
• adverse effects
  • generally well tolerated
  • headaches and flushes may occur
  • tachycardia / palpitations
  • leg oedema - less so with the newer lercanidipine
  • rarely, HS reactions
• nifedipine: (Adalat)
• nimodipine:
  • may be some selectivity for cerebral vessels
• nicardipine:
  • may be some coronary selectivity for vasodil. ⇒ nifedipine;
  • a little less -ve inotropy cf nifedipine;
  • → incr. exercise tolerance & decr. angina in pts with effort-angina;
• felodipine: (Plendil ER)
  • peak 3-5hrs; once daily if ER as pre-systemic metabolism resulting in 20% bioavail. & minimising post-absorption peak;
  • 99% plasma protein bound;
  • Extensively metabolised by liver;
• amlodipine: (Norvasc) Aust. '94;
  • peak blood levels 6-12hrs post-dose - shorter (6-8hrs) if hepatic insufficiency
  • once daily dosing; steady state by 7-8days;
  • 97.5% plasma protein bound; Vd ~20 l/kg; metab. by liver;
• lercanidipine (Zanidip):
  • newer generation with apparently less leg oedema

• bepridil:
• perhexiline maleate:
  • used in refractory cases of angina where:
    • awaiting revascularisation in whom Rx will be < 3 months duration, or,
    • long term Rx in pt who is unsuitable or unwilling to have revascularisation.
  • need to measure plasma levels:
    • Rx range:
      • 0.15-0.6mg/L - adequate for most
      • 0.6-1.2mg/L - for those not responding to above dose range
    • Toxicity:
      • > 1.2mg/L ⇒ hepatotoxicity, peripheral neuropathy (if chronic high levels)
  • adverse effects in Rx range:
    • 60% have some dose dependent adverse effects but most are mild:
      • dizziness, nausea during loading phase
    • diabetics may develop hypoglycaemia in 1st few days Rx
  • relative C/I's:
    • liver disease
    • peripheral nerve disease
    • ~10% popn are slow metabolisers of perhexilene & require very low maintenance doses (eg. 50-100mg once weekly).
      • these pts can be idientified by relatively high plasma concentrations after the initial week's Rx together with absence of detectable circulating metabolite
  • administration:
    • 200mg orally bd for 3 days, then,
    • 200mg daily after taking a blood sample
    • further dose adjustments at monthly intervals should be based on plasma levels
    • usual maintenance dose: 100-400mg daily aiming for plasma level 0.15-0.6mg/L
• flunarizine:

• Exertional Angina:
  • see angina
• Supraventricular tachycardia:
  • see SVT
  • mainly verapamil
• Hypertension:
  • see hypertension
• Hypertensive crises:
  • esp. the dihydropyridines in perioperative HT:
  • as effective as nitroprusside, trimetaphan or nitrates & safer;