Verapamil

Verapamil

Chemical

Synthetic papaverine derivative

Use

  1. Hypertension
  2. Angina
  3. SVT

Presentation

Tablets

Racemic mixture → solution for injection

L isomer = inhibits Ca2+ influx across slow (L type) Ca2+ channels

D isomer = no Ca2+ blocking activity; mimics LA at fast Na+ channels

Dose

PO: 250 – 480mg (divided doses)

IV: 5 – 10mg over 30 sec

→ PO dose much higher than IV dose due to extensive 1st pass metabolism

Route

PO: 240 – 480mg

IV: 5 – 10mg → then can infuse 5mcg/kg/min to sustain effect

Onset

IV peak effect 3 mins

DoA

20 mins

MoA

  • Competitive antagonist at L-type Ca2+ channels
  • ↓Ca2+ influx into vascular smooth m. & myocytes
  • Inhibits contraction

Verapamil’s predominant effect is at AV node, but also SA node, myocardium, peripheral vessels

PD

CVS:

  • Class & antiarrhythmic
  • ↓automaticity (↓Ph 4 depolarisation)
  • ↓conduction velocity
  • ↑refractory period
  • AV conduction slowed
  • – ve inotrope
  • Vasodilation arterioles → ↓BP
  • Potent CA vasodilation

CNS: Cerebral vasodilation

GU: ↑RBF 2° ↓ vascular resistance

PK

A

20% OBA

Significant 1st pass

D

>90% PPB (all CCBs)

VD 5L/kg

M

Demethylation & dealkylation in liver

Norverapamil = activity

E

70% metabolites excreted in urine

16% metabolites excreted in faeces

t ½ B 6hrs

Adverse Effects

  • Hypotension
  • Profound -ve inotropy with overdose

Multiple drug interactions

  • Potentiate NMBD
  • Volatiles → -ve inotropy
  • ↑risk LA toxicity with verapamil
  • ↑[Digoxin] levels ∴↑ risk toxicity
  • Huge additive -ve chrono & inotropic effect in conjunction with β blockers