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calciumblockers

calcium channel blockers

see also:

high specificity calcium channel blockers:

  • act via specific membrane sites;

non-dihydropyridines:

Phenylalkylamine group:
  • 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)
Benzothiazepine group:
  • marked suppression of SA automaticity;
  • moderate suppression of SA conduction;
  • moderate coronary vasodilatation;
  • mild -ve inotropy;
  • diltiazem: (Cardizem)
    • ie. similar effects to verapamil;
T-gated blockers:
  • mibefradil: [Posicor]
    • less -ve inotropy?
    • still suppress AV node

Dihydropyridine group:

  • 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
    • 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)
    • 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

low specificity calcium antagonists:

  • 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:

clinical uses of calcium antagonists:

  • Exertional Angina:
  • Supraventricular tachycardia:
    • see SVT
    • mainly verapamil
  • Hypertension:
  • Hypertensive crises:
    • esp. the dihydropyridines in perioperative HT:
    • as effective as nitroprusside, trimetaphan or nitrates & safer;
calciumblockers.txt · Last modified: 2020/03/19 21:30 (external edit)