SEDATIVE, CO-INDUCTION AGENT, PRE-MED, ANXIOLYTIC, AMNESIC
0.5mg/kg PO pre-op for anxiolysis
0.25-0.5mg/kg IV for sedation
IV onset over 90s. Peak at 2-5mins. Duration of 1-2h.
Presence of imidazole ring = act as a structural isomer = tautomerism (changes physical properties by changes in physical environment).
Binds to benzo binding site on GABA-A
Increased frequency of chloride channel opening = increased intracellular chloride transmission.
GABA-A is a large unit with also sites for profofol, alcohol and barbitutes
= explaining synergy and use of benzo’s in withdrawal.
The benzodiazepine antagonist flumazenil occupies the
benzodiazepine binding site but produces no activty.
Caution in Young, Elderly & Renally Impaired - elimination impaired.
Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam by the liver.
There can be a paradoxical increase in activity/agitation in the young and old.
Used from 1976
Side effects can include apnoea, decreased respiratory effort, low BP and sleepiness
Stacking phenomenon - incremental doses of midazolam can 'stack' due to its relatively long duration/onset - notable during short procedures... then the stimulus is removed (OGD) and the effect of the drug is constantly accumulating...
Dr. David Lyness
60p for 5mg
(max 20mg PO)