Midazolam: The First Water‐soluble Benzodiazepine; Pharmacology, Pharmacokinetics and Efficacy in Insomnia and Anesthesia

Abstract

Midazolam is a 1,4-benzodiazepine derivative with a unique chemical structure: depending on environmental pH, the drug can produce highly water-soluble salts (pH less than 4) or exist in lipophilic diazepine ring-closed form (pH greater than 4). This characteristic contributes to rapid onset of action and to good local tolerance after parenteral administration. After both oral and parenteral administration, midazolam has a fast absorption rate and is rapidly excreted, with a half-life of only about 2 hours. A reasonably good correlation has been found between plasma levels and clinical effects, indicating a fast but brief response. As a hypnotic, midazolam is mainly indicated in insomniac patients with difficulties in falling asleep or having a pathologic sleep pattern during the first half of the night. No marked hangover effects are present the next morning. In anesthesiology, midazolam appears to be a useful, short-acting, sedative-anxiolytic and amnesic premedicant after both oral and parenteral administration. In minor surgery, however, the slow, unpredictable onset and variable duration of action, as compared with thiopental, may inhibit its routine use as an induction agent, especially in young patients, without heavy premedication. In major surgery, midazolam is an alternative to thiopental for induction of anesthesia in spite of its slow, variable induction time. Its advantages include good cardiovascular stability, transient and mild respiratory depression, low frequency of venous irritation, production of anterograde amnesia and short duration of action in comparison with other benzodiazepines.

Is cyclosporin A an inhibitor of drug metabolism?

“…Such plasma drug concentration-effect relationships have been described previously in healthy volunteers (Allonen et al, 1981) as well as in surgical patients (Persson et al, 1988). Likewise, the sedative effects were of short duration confirming the findings of others (Allonen et al, 1981;Dundee et al, 1984;Kanto, 1985;Kassai et al, 1988;Klotz & Ziegler, 1982;Persson etal., 1988;Reves et al, 1985). Hence the pharmacokinetic and pharmacodynamic measurements both suggest that the dosage of midazolam needs no adjustment when it is administered to patients receiving treatment with cyclosporin A.…”

“…Midazolam appears, Allonen et al (1981); Klotz & Ziegler (1982); Kanto (1985); Reves et al (1985); Dundee et al (1984); Kassai et al (1988); Persson et al (1988). KS-v vided) upon addition of cyclosporin A to liver microsomes obtained from phenobarbitoneinduced male rats (Augustine & Zemaitis, 1986).…”

Lift of cheek and neck: technical notes

“…During this time the skin is marked for the incision and prepping and draping are performed. The half-life of midazolam is 2-6 h. [13] The goal is to achieve a co-operative, oriented and calm state (level 2 on the Ramsey Scale of Sedation). [14] The patient should still be able to respond normally to verbal stimuli (i.e.…”

Le midazolam. 1repartie : pharmacologie

“…En général, 5-6 h après une dose unique de midazolam, le midazolam n'est plus décelable dans la circulation sanguine. Ce phénomène permet d'éviter des effets indésirables résiduels [16].…”