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)