2005B07 Briefly outline the pharmacology of droperidol, emphasising its
mechanism of action, peri-operative use and side effects.

Class

·   Butyrophenone

Presentation

·   Aqueous solution

·   Light-protected ampoule

Administration

·   IV, IM, PO

Time course

·   Onset 5-15 mins

·   Duration: up to 12 hours for sedative effect

Absorption

·   Oral bioav 75%

Distribution

·   Plasma protein binding 85-90%

·   V_D 1.5-2.5L/kg

Metabolism

·   Hepatic CYP450

·   Clearance 8mL/kg/min (slow)

·   t_1/2β 2 hours

Excretion

·   1% unchanged in urine > faeces

·   Metabolites > urine

Mechanisms

·   Central DA₂ antagonist (Binds G_i GPCR -> ↓cAMP)

·   ↓Afferents from chemoreceptor trigger zone to vomiting centre

·   α-adrenoceptor antagonist

Use (dose)

·   PONV prevention or rescue (0.5-0.625mg in adults)

·   Anti-psychosis, chemical restraint )1.25-2.5mg slowly IV, q10 mins; max 10mg)

·   Neuroleptanaesthesia

Side effects

·   Sedation

·   Mild hypotension

·   EPSE:

o  Parkinsonism (tremor)

o  Akathisia (restlessness)

o  Tardive dyskinesia (rhythmic voluntary movements of the tongue, face and jaw)

o  Acute dystonia (e.g. oculogyric crisis)

·   Neuroleptic malignant syndrome

·   ↑QT_C, ↑risk torsades de pointes