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HYDRALAZINE

CLASS

Antihypertensive, vasodilator

PRESENTATION

White lyophilised powder, tablets

Formulations

  • 20mg vial

INDICATIONS & DOSING

Hypertension (including pre-eclampsia)

  • Adult; 5-20mg IV bolus, max 40mg
  • Adult infusion; IV infusion 50-300mcg/min IV
  • Paediatric; 0.1-0.2mg/kg IV bolus, max 0.4mg/kg

Blunting of the sympathetic response to intubation

  • Adult; 30-40mg IV bolus 10 minutes prior to intubation
  • Paediatric; 0.4mg/kg IV bolus 10 minutes prior to intubation

PRACTICALITIES

Administration

  • 20mg hydrazine in N/saline up to 10ml; 2mg/ml

Incompatibilities

  • Glucose-containing solutions; inactivation of hydralazine

Practice tips

  • Delayed onset (maximum effect at 20 minutes) can result in dose-stacking and hypotension if repeat doses are given too early – consider using an alternative agent if a more rapid onset is desirable
  • Beta-blockade has been used to counteract the compensatory tachycardia as this limits the clinical effectiveness of vasodilation

PHARMACOKINETICS

Onset

  • IV; 10-20min

Duration of action

  • IV; 2-6 hours

Metabolism

Majority hepatic metabolism. Genetic variability apparent in oral absorption and metabolism secondary to acetylator status.

Elimination

Majority renal excretion of metabolites.

MECHANISM

Multiple mechanisms of action; hyper-polarisation of smooth muscle cells secondary to K+ efflux, activation of guanylate cyclase leading to an increase in intracellular cGMP, and inhibition of calcium movement and intracellular [Ca++]. Net effect is a reduction in vascular smooth muscle tone.

DESIRED CLINICAL EFFECTS

Cardiovascular

  • Antihypertensive effect; reduction in blood pressure (diastolic>systolic)

Neurological

  • Preserved cerebral blood flow

Renal

  • Preserved renal blood flow

OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES

Cardiovascular

  • Flushing, sweating 
  • A ‘hyperdynamic circulation’; hypotension, compensatory tachycardia, increased cardiac output
  • Precipitation of myocardial ischaemia
  • RV failure due to pulmonary hypertension secondary to increased cardiac output without pulmonary vasodilation (rare) 

Neurological

  • Neurological
  • Headache
  • Peripheral neuropathy (chronic) 

Renal & electrolytes

  • Increased plasma renin, sodium retention, water reabsorption, oedema 

Gastrointestinal

  • Nausea, vomiting, diarrhoea, loss of appetite 

Haematological

  • Blood dyscrasias – agranulocytosis, leukopenia (chronic) 

Other

  • SLE-like syndrome (chronic)

CONSIDERATIONS

Precautions

  • Hepatic and renal impairment
  • Severe tachycardia, hyperdynamic circulatory states
  • Ischaemic heart disease
  • Clinically significant outflow obstruction (e.g. MS, AS, HOCM)
  • Pulmonary hypertension
  • Dissecting aortic aneurysm
  • Porphyria 

Obstetric 

ADEC category C (foetal tachycardia, potential for teratogenicity) 

Drug interactions

  • Antihypertensives including general anaesthesia; potentiates hypotensive action
  • MAO-inhibitors; potentiates hypotensive action
  • Metoprolol; enhanced oral bioavailability and action of metoprolol

REFERENCES

Drug information has been compiled from multiple sources including

  • Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
  • Micromedex (IBM)
  • BJA Education (Oxford Academic)
  • Pharmacology for Anaesthesia and Intensive Care (Cambridge)
  • Australian Prescriber (NPS MedicineWise)

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