- Malignant hyperpyrexia
- Neuroleptic malignant syndrome
- Chronic spasticity of voluntary muscles
- Ecstasy intoxication
Dantrolene
Dantrolene
Presentation
- Presents as an orange powder containing:
- 20mg dantrolene
- 3mg mannitol
- NaOH
- Reconstituted with 60ml water to produce a pH 9.5 solution
Dosing
- For management of malignant hyperpyrexia:
- 2.5mg/kg bolus dose
- Repeat 1mg/kg boluses every 5-10mins until resolution
- Theoretical maximum dose of 10mg/kg
Absorption
- Variable oral bioavailability, approximately 70%
Distribution
- 85% albumin bound
- Crosses the placenta; neonatal plasma dantrolene levels 65% of maternal levels
Metabolism
- Hepatic metabolism to the active metabolite 5-hydroxydantrolene, which has some skeletal relaxant properties
- Further metabolism to aminodantrolene and a reduced, acetylated derivative
Excretion
- Plasma elimination half-life of 12hrs
- Mostly excreted in urine and bile
Respiratory
- Can produce respiratory failure secondary to skeletal muscle weakness (3%)
- Chronic use can lead to pleural effusions
Neurological
- Primary mechanism of action
- Binds the ryanodine receptor and uncouples the excitation-contraction process
- Has no effect on cardiac and vascular smooth muscle as they aren't primarily dependent on calcium release for contraction
- No affect on muscle action potentials
- Little effect on the clinical duration of non-depolarising NMBA, but can act synergistically
- Muscle weakness (22%)which persists for up to 48hrs
- Use associated with drowsiness, dizziness and confusion (possibly relating to altered neuronal calcium homeostasis)
Renal
- Causes diuresis (because of the mannitol present)
Gastrointestinal
- GI discomfort (3%) inc. nausea, diarrhoea
- Chronic oral use can lead to hepatitis
Adverse features
- Causes phlebitis (10%) due to the alkaline nature of the solution
- Highly irritant if extravasated