Potassium channel activators  EXAMPLES 

Nicorandil
MECHANISM OF ACTION 

  • Dual mechanism of action.
  • Opens ATP-sensitive Kþ channels resulting in smooth muscle relaxation, thereby promoting arterial vasodilatation and reducing afterload.
  • Nitric oxide moiety activates guanylyl cyclase to achieve venous relaxation and a reduction in preload.
  • Direct effects on coronary arteries are also seen.

INDICATIONS

  • Prophylaxis and treatment of angina

CAUTIONS AND CONTRA-INDICATIONS

  • Cardiogenic shock.
  • Hypotension.
  • LVF with poor filling pressures

SIDE-EFFECTS

  • Headaches on initiation.
  • Nausea and vomiting.
  • Dizziness.
  • Flushing.
  • Weakness.
  • Oral ulceration.
  • Angioedema.

METABOLISM AND HALF-LIFE

  •  t½ is 40–80min. Metabolised by the liver via nicotinamide pathway; <20% excreted in the urine.

MONITORING 

  • Monitor clinically for adverse effects.

DRUG INTERACTIONS

  • Hypotensive effects significantly enhanced when taken with phosphodiesterase type 5 inhibitors (e.g. sildenafil).
  • Hypotensive effects possibly enhanced with tricyclic antidepressants and alcohol.

IMPORTANT POINTS

  • Start at a lower dose in patients susceptible to headaches.
  • Patients are advised not to drive or operate machinery until it is established that their performance is unaffected.
  • Titrate dose to symptomatic relief.
  • Used as an add-on therapy