CAPTOPRIL

PHARMACOLOGY AND PHARMACOKINETICS

Captopril acts by competitively inhibiting the angiotensin converting enzyme (ACE), which converts angiotensin I to angiotensin II. Angiotensin II is not only a potent endogenous vasoconstrictor, but it also stimulates aldosterone secretion from the adrenal cortex. Increased aldosterone leads to sodium and water retention, increased blood volume and thus increased blood pressure. Therefore by reducing angiotensin II, blood pressure is lowered by two mechanisms: less direct vasoconstriction and less sodium and water retention via aldosterone.

Approximately 60 to 75% of an oral dose of Captopril is absorbed from the gastrointestinal tract. It is about 30% bound to plasma proteins. It is largely excreted in the urine 40 to 50% as unchanged drug and as metabolites. The elimination half-life has been reported to be 2 to 3 hours but this is increased in renal failure.

INDICATIONS

  • Hypertension: Captopril is used as an adjunct in the treatment with a thiazide diuretic in mild to moderate hypertension in severe hypertension resistant to other treatment.
  • Congestive heart failure: Captopril is used as an adjunct in the treatment of severe congestive heart failure.

DOSAGE

The dosage of Captopril must be individually titrated to clinical response in each patient.

  • Hypertension. In the treatment of hypertension the initial dose is 12.5mg two times daily by mouth, increased gradually according to the response of the patient. In mild to moderate hypertension the usual maintenance dose is 25mg two times daily and should not exceed 50mg twice daily. In severe hypertension a dose of 50mg three times daily should not be exceeded.
  • Congestive heart failure. The initial dose is 6.25 to 12.5mg three times daily. The dose may be increased to 25 mg three times daily with careful monitoring. The first dose should be given under supervision. Elderly patients should be given the first treatment from hospital. Captopril is not recommended in patients with renal impairment. Where it is clinically indicated in severely hypertensive patients with impaired renal function, the dose should be kept as low as possible. In these patients a loop diuretic rather than a thiazide should be used.

SIDEEFFECTS

The side-effects of Captopril can be broadly grouped into those caused by allergic reactions and those due to excessive pharmacological effects.

  • The allergic reactions are most commonly manifested as urticarial rashes and fevers. Less common but severe effects reported thus far include pancytopenia, agranulocytosis, leukopenia, nephrotic syndrome, membranous glomerulopathy and pemphigus.
  • The reactions caused by pharmacological effective doses include a low incidence of orthostatic hypotension, tarchycardia and rarely ischaemic damage to the heart or kidneys secondary to vasopressive effects.
  • Ageusia (loss of taste) is a common adverse effect which resolves spontaneously in some patients.
  • Proteinuria has also been reported.

PRECAUTIONS AND SIDE EFFECTS

  1. Captopril should be used with great caution in patients with impaired renal function particularly if renovascular disease is present or suspected and in patients with collagen disorders such as systemic lupus erythematous or scleroderma. Renal function should be assessed in all patients prior to administration of Captopril. Patients with existed renal disease or taking high doses of captopril should be monitored regularly for proteinuria.
  2. Regular white blood cell counts should be made during the initial stages of therapy particularly in patients with collagen vascular disorders or impaired renal function and in patients receiving immunosuppressive therapy.
  3. Patients with congestive heart failure and patients who are likely to be salt or water depleted due to concomitant treatment with diuretics or dialysis may experience symptomatic hypotension during the initial stages of captopril therapy. This may be reduced by starting with a low dose, preferably on retiring.
  4. Pregnancy. When used during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing foetus. When pregnancy is detected this drug should be discontinued as soon as possible.
  5. Breastfeeding. Because Captopril is excreted during breast milk, Captopril should not be used during breast feeding.
  6. Children. Safety and effectiveness in children has not been established. Captopril is not recommended for use in children.
  7. Dry cough may occur when using this medicine.

DRUG INTERACTIONS

  • Diretics/hypotensives enhance the hypotensive effect.
  • Hypokalaemia may occur with potassium sparing diuretics or potassium supplements.
  • NSAIDs may reduce the antihypertensive effect.
  • Probenacid reduces the renal clearance of Captopril.
  • There have been reports on neutropenia and/or Steven Johnson’s syndromes in patients on Captopril plus either Allopurinol or Procainamide.
  • Initiation of Captopril has been associated with unexplained hypoglycaemia in several diabetics on insulin or oral hypogylcaemics.
  • Neuropathy developed in 2 patient receiving Captopril and Cimeditine.

DRUG / LABORATORY TEST INTERFERENCES

A reversible elevation of BUN and serum creatinine levels may occur in volume-depleted patients or in those with renal disease. Captopril may cause false positive results in tests for acetone in urine.

CONTRA-INDICATIONS

Captopril is contra-indicated in patients with a history of previous hypersensitivity to Captopril.

OVERDOSAGE.

Volume expansion with intravenous infusion of Sodium Chloride injection is recommended for the treatment of hypotension. Captopril is removed by dialysis.