Neurosurgery notes/Pharmacology/Pharmacology general/Ca Channel blockers

Ca Channel blockers

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Pharmacology general

L-type calcium channel blockers (L=Long lasting)

Dihydropyridines

  • Predominantly vasodilators and generally have limited chronotropic and inotropic effects
  • Nicardipine
    • A dihydropiridine calcium channel blocker which acts preferentially on vascular smooth muscle more than cardiac smooth muscle.
    • Restores vessels to at least 60% of normal diameter.
    • 70% of those treated had no stroke on CT.
    • May cause a drop in SBP, but not> 30%.
    • ℞
      • Intra-arterial therapy: 10–40mg per procedure.
        • Three retrospective case series have reported vessel dilation and transient improvement in neuro deficits.
      • Intraventricular nicardipine
        • Treat severe vasospasm in doses of 4 mg every 12 hours for 5 to 17 days
    • Why is nicardipine a good alternative to manage hypertension in neurovascular pathologies (e.g., TBI, subarachnoid haemorrhage, intraparenchymal haemorrhages)
      • Short-acting continuous-infusion agent
      • A reliable dose–response relationship
      • Favorable safety profile.
      • It has been shown to reverse vasospasm
  • Nimodipine
    • See Das 2024
    • Indication
      • Prevention and treatment of cerebral vasospasm following subarachnoid hemorrhage
      • Given intra-arterially to reverse vasospasm
      • No proven benefit
        • Post stroke
          • INWEST Trial 1994
            • A potential neuroprotective effect of nimodipine by preventing calcium overload in ischaemic neurons may thus have been outweighed by detrimental haemodynamic effects in the ischaemic area.
        • Post Head injury
      • Small vessel subcortical vascular dementia (Pantoni 2000)
    • Dosage
      • SAH Vasopasm prevention
        • BANT 60 mg every 4 hours given orally
        • Kronvall 2009 Oral and intravenous nimodipine are equally efficient in preventing vasospasm following subarachnoid haemorrhage.
    • Mechanism of action
      • Block voltage-gated L-type calcium channels → prevent influx of calcium ions → prevent vasoconstriction.
      • Other
        • Enhance neuroprotection via reducing Ca Cytotoxicity
      • Preferentially acts on cerebral blood vessels
      • Lipophilic and can cross the blood-brain barrier hence better than other L type Ca channel blocker
    • Pharmacokinetics
      • Absorption
        • Rapidly absorbed after oral administration,
        • Peak concentrations achieved within 0.5 to 1.5 hours.
        • Has high first-pass metabolism
          • The bioavailability of nimodipine is approximately 13% after oral administration
          • Simultaneous administration of breakfast results in decreased peak plasma concentration and lower bioavailability relative to fasting conditions.
      • Metabolism
        • Extensively metabolized by CYP3A4 and CYP3A5.
      • Elimination
        • Half-life of nimodipine is approximately 8 to 9 hours
          • Initial elimination is rapid (equivalent to a half-life of 1-2 hours)
            • Consequently, there is a need for frequent (every 4 hours) dosing
        • Excreted via the kidney
    • Side effects
      • Headache
      • Vertigo
      • Flushing
      • Nausea
      • Diarrhea
      • Pedal edema
      • Rash
      • Palpitations.
    • CI
      • Use within 1 month of myocardial infarction
      • Unstable angina
      • Acute porphyria.
      • Should not be used concurrently with phenobarbital, phenytoin or carbamazepine.
    • Use in pregnancy is advised if potential benefits outweigh risks.
      • There is no available evidence of effects when breast feeding.

Non-dihydropyridines

  • Less potent vasodilators and also slow cardiac contractility and conduction
  • Verapamil
    • The primary drug employed
  • Diltiazem

N-type Ca²⁺ channels blockers (N=Neuronal)

Thalamic T-type Ca²⁺ channels blockers (T=Transient)