Pharmacology Benzodiazepines

Benzodiazepines act within the central nervous system (CNS) at specific benzodiazepine receptor sites. Occupation of these receptors results in augmentation of y-aminobutyric acid, which is an inhibitory neurotransmitter resulting in depression of cortical function. Thus, benzodiazepines result in a dose dependent continuum of effect from mild sedation through drowsiness and sleep to deep sedation. They produce sedation, anxiolysis, and amnesia.

Midazolam

Midazolam is the preferred benzodiazepine of choice for sedation because of its rapid onset of action (3 to 5 minutes), short half-life (1.8 to 6.4 hours), and better antegrade amnesia properties. Dosing based on an otherwise healthy patient is 0.03 mg/kg as an initial dose over 2 minutes. Initial dosing should not exceed 2.5 mg for patients under 60 years of age, and 1.5 mg for patients over 60 years of age. Additional midazolam may be given in 0.25 to 1 mg to maintain the desired level of sedation. Subsequent doses should be separated by at least 2 to 3 minutes (Johns Hopkins, 2001). A total dose of < 5 mg is usually adequate for sedation in most patients; however, a higher dose may be necessary in longer procedures and in the individual patient. Midazolam is metabolized to 1-hydroxymethyl-midazolam, which is rapidly conjugated in the liver and then excreted renally. Renal insufficiency does not require dose modification. Smaller doses should be used in older, debilitated, or chronically ill patients, and in patients with hepatic insufficiency.

IV midazolam has been associated with respiratory depression, especially when combined with a narcotic. Other adverse effects include hiccoughs, nausea and vomiting, and tenderness at the IV site. Paradoxical reactions, such as agitation, hyperactivity, and combativeness, have been reported in patients with alcohol and substance abuse.

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