- Benzodiazepines
- Drugs with psychoactive, sedative, anxiolytic, hypnotic, anterograde amnesic, anticonvulsant and muscle relaxing properties
- Act via BDZ receptors in the cortex and midbrain and closely linked with GABA & facilitates GABA by binding to the α subunit which increases the affinity of GABA for its receptor
- Classified according to T½
- Short (<12 hrs)
- Medium (12-24 hrs)
- Long (>24 hrs)
- GABA receptors
- GABA(A)
- Ligand gated Cl⁻ channel, pentameric structure with 2α/β/γ/δ subunits. They are sub-classified according to specific α units
- Type 1
- Found in spinal cord and cerebellum
- Cause anxiolysis
- Type 2
- Found in spinal cord, hippocampus and cortex
- Cause sedation and anti-convulsant effect
- GABA(B)
- Gq linked, metabotropic which increases K⁺ conductance causing hyperplolarisation
- Found pre- and post- synaptically
- Baclofen acts at GABA(B)
- Poisoning
- Monitor ECG, SpO₂, BP
- Consider charcoal
- Flumazenil
- T½(e) 40-80 mins
- Imidazobenzodiazepine derivative
- 0.1-0.2mg - partial antagonism
- 0.4-1mg - complete antagonism
- Onset of reversal at 1-2mins
- 80% response at 3 mins, peak effect at 6-10 mins
- 50% protein bound
- Hepatically metabolised
- Midazolam
- At pH 3.5 it has an open ring structure and is water soluble
- Tautomerism if pH is > 4 at which point the ring closes and becomes lipid soluble
- pKa 6.5
- 90% unionised at pH 7.4
- T½(e) 1-4 hrs
- Clearance ~ 6-10ml/kg/min
- Reduces MAC by ~ 15%