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Nesiritide

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Recombinant human B-type (brain) natriuretic peptide

Mode of action

  • vasodilatory, natriuretic and diuretic effects
  • primarily mediated via natriuretic peptide receptor A on vascular smooth muscle, endothelium, kidneys and adrenals
  • no direct inotropic effect
  • ± reduces aldosterone and inhibits plasma renin activity

Pharmacokinetics

  • administration: IV infusion
  • distribution
    • distribution t1/2 ~2 mins
    • mean volume of distribution at steady state 0.19 l/kg
  • elimination by multiple routes:
    • after binding to cell surface natriuretic peptide receptor C nesiritide is internalized and degraded
    • hydrolysis by endopeptidase
    • renal filtration
  • elimination t1/2 ~18 mins
  • clearance proportional to body weight (~0.55 l/h/kg)
  • dosage adjustment not required in patients with renal dysfunction

Clinical indications

  • acute decompensated heart failure with dyspnoea on minimal exertion or at rest
    • reduces preload. Rapid reduction in pulmonary capillary wedge pressure (faster than glyceryl trinitrate) and right atrial pressure
    • reduces afterload resulting in increase in cardiac output
    • diuresis & natriuresis
    • 6 month mortality similar to patients treated with nitrate but lower than those treated with dobutamine
  • contraindicated in cardiogenic shock or in patients with systolic BP <90 mmHg

Adverse effects

Cardiovascular

Similar incidence to patients treated with nitrate.

  • hypotension
    • usually resolves spontaneously or responds to fluid challenge of 250 ml or less
    • duration of episode longer than hypotensive episodes associated with glyceryl trinitrate
  • not proarrhythmic

Non-cardiovascular

Less common than with glyceryl trinitrate

  • general pain
  • abdominal pain
  • catheter-related pain
  • headache
  • nausea

Drug interactions

  • does not interact with enalapril
  • interactions with IV vasodilators (including IV ACE inhibitors) and other cardiovascular drugs have not been formally studied

Dosage & administration

  • bolus of 2 mcg/kg followed by infusion of 0.01 mcg/kg/min
  • reduce dose/discontinue if hypotension occurs
  • should only be used in pregancy if potential benefit to mother outweighs potential risk to fetus
  • administer with caution to breastfeeding mothers

Further reading

Keating GM, Goa KL. Nesiritide. A review of its use in acute decompensated heart failure. Drugs, 2003; 63(1):47-70


 

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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