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

 

List:

·     PC

·     PK

·     PD

 

Physicochemical:

Class

·  Butyrophenone

Presentation

·  Aqueous solution

·  Light-protected ampoule

 

Pharmacokinetic:

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%

·  VD 1.5-2.5L/kg

Metabolism

·  Hepatic CYP450

·  Clearance 8mL/kg/min (slow)

·  t1/2β 2 hours

Excretion

·  1% unchanged in urine > faeces

·  Metabolites > urine

 

Pharmacodynamic:

Mechanisms

·  Central DA2 antagonist (Binds Gi 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

·  ↑QTC, ↑risk torsades de pointes