SHORT ACTING BENZODIAZEPINE.
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).
Due to this tautomerism, it's imidazole ring opens up when moved from vial where its pH is 4, into physiological pH (becomes water soluble!)
Oral bioavailability is 40–50%. Unlike diazepam, intramuscular absorption is rapid.
Undergoes hepatic oxidative metabolism and has an elimination half-life of 2 h.
The major metabolite, hydroxymidazolam, has a half-life of around 1 h, and is biologically active – beware in renal impairment.
Midazolam is 1.5 – 2x more potent than diazepam & much more favourable pharmacokinetics
for use as a short-term IV sedation.
Binds to benzo binding site on GABA-A
Increased frequency of chloride channel opening = increased intracellular chloride transmission.
Sites are found mostly in cerebral cortex and then cerebellum and hippocampus – lowest in the medulla.
Few non-CNS binding sites = good cardiac stability.
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.
Can cause seizures.
Midazolam has important anterograde amnesic qualities.
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)