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Isosorbide mononitrate

Class
Indications
  • Prophylactic prevention of angina pectoris due to coronary artery disease
  • Treatment of acute and chronic angina pectoris, hypertension, and myocardial infarction
Administration/Absorption
  • Oral
  • 100% absorbed
Dosage
  • 20 - 120 mg
Distribution
  • VOD 0.6 to 0.7 L/kg
  • 5 % protein bound
Mechanism
  • Similar to other nitrites and organic nitrates, Isosorbide Mononitrate is converted to nitric oxide (NO)
    • Active intermediate compound which activates the enzyme guanylate cyclase (Atrial natriuretic peptide receptor A).
  • This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP)
    • This activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells
    • Eventually results in the dephosphorylation of the myosin light chain of the smooth muscle fiber.
  • The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.
  • By dilating the vessels, it lowers the blood pressure and reduces the left ventricular preload and afterload, therefore, leads to a reduction of myocardial oxygen requirement
Excretion
  • Isosorbide mononitrate is primarily metabolized by the liver, but unlike oral isosorbide dinitrate, it is not subject to first-pass metabolism.
  • Isosorbide mononitrate is cleared by denitration to isosorbide and glucuronidation as the mononitrate
    • 96% of the administered dose excreted in the urine within 5 days and only about 1% eliminated in the feces
  • At least six different compounds have been detected in urine, with about 2% of the dose excreted as the unchanged drug and at least five metabolites.
  • Half-life 5 hours
Side effects
  • Very common
    • Headache predominates (up to 30%) necessitating withdrawal of 2 to 3 % of patients, but the incidence reduces rapidly as treatment continues .
  • Common
    • Tiredness, sleep disturbances (6%) and gastrointestinal disturbances (6%) have been reported during clinical trials with isosorbide mononitrate modified release tablets, but at a frequency no greater than for placebo.
    • Hypotension (4 to 5%), poor appetite (2.5%), nausea (1%).
  • Hypotension (4%) with symptoms such as dizziness and nausea (1%) have been reported.
    • These symptoms generally disappear during long-term treatment.
  • Other reactions that have been reported with isosorbide mononitrate modified release tablets include tachycardia, vomiting, diarrhoea, vertigo and heartburn
Interactions

Contraindications

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