Benzodiazepines Midazolam (Versed) Diazepam (Valium) Lorazepam (Ativan) Anxiolytics Sedation Same Same Anticonvulsant Clinical Uses Anterograde amnesia Least amnestic effect Greatest sedative and amnestic effect Used pre-op, conscious sedation, induction and maintenance Enhance GABA binding to beta site on GABA receptor complex Mechanism of Same Same Action Benzo. Receptor site on alpha subunit of GABA receptor complex (post synaptic Nerve endings in the CNS) Versed = water soluble benzodiazepine w/ imidazole ring - rapid metabolism Structure acidic IV solution pH 3.5 – ring open H2O sol. – at pH > 4 ring closes now lipid soluble high 1st pass hepatic effect only 50% Rapidly absorbed via GI Slow – reaches circulation Highly protein E1/2x = 10-20 highly protein bound cirrhosis/RI – →dec. albumin→ increased risk of side effects Peak in 1 hr. for adults; 15-30 min for peds. slow effect site equil. Time (0.9-5.6 min) Metabolized by hepatic microsomal enzymes Pharmacokinetic Active metabolite return of drowsiness → short DOA 2nd high lipid solubility (rapid hrs later redistribution) and rapid metabolism by cytochrome P450 E1/2 x = 21-37 hours Valium has longer E1/2x but shorter DOA E1/2x 1-4 hours than versed b/c it dissolves more rapidly from GABA receptors→more rapid redistribution Do not use w/ 1st trimester pregnancy – birth defects Contraindication Same Same Careful w/pediatric + elderly E1/2x is doubled in elderly Benzodiazepine Midazolam (Versed) Diazepam (Valium) Lorazepam (Ativan) Crosses BBB Neuro Decreased motor coordination and impaired cognition
Benzodiazepines Midazolam (Versed) Diazepam (Valium) Lorazepam (Ativan) Clinical Uses Anxiolytics Sedation Anticonvulsant Anterograde amnesia Used pre-op, conscious sedation, induction and maintenance Same Least amnestic effect Same Greatest sedative and amnestic effect Mechanism of Action Enhance GABA binding to beta site on GABA receptor complex Benzo. Receptor site on alpha subunit of GABA receptor complex (post synaptic Nerve endings in the CNS) Same Same Structure Versed = water soluble benzodiazepine w/ imidazole ring - rapid metabolism acidic IV solution – pH 3.5 ring open – H2O sol. at pH > 4 ring closes now lipid soluble Pharmacokinetic high 1st pass hepatic effect – only 50% reaches circulation highly protein bound – cirrhosis/RI →dec. albumin→ increased risk of side effects slow effect site equil. Time (0.9-5.6 min) short DOA 2nd high lipid solubility (rapid redistribution) and rapid metabolism by cytochrome P450 E1/2x 1-4 hours Rapidly absorbed via GI Highly protein Peak in 1 hr. for adults; 15-30 min for peds. Metabolized by hepatic microsomal enzymes Active metabolite → return of drowsiness hrs later E1/2 x = 21-37 hours Valium has longer E1/2x but shorter DOA than versed b/c it dissolves more rapidly from GABA receptors→more rapid redistribution Slow E1/2x = 10-20 Contraindication Do not use w/ 1st trimester pregnancy – birth defects Careful w/pediatric + elderly E1/2x is doubled in elderly Same Same Benzodiazepine Midazolam (Versed) Diazepam (Valium) Lorazepam (Ativan) Neuro Crosses BBB Decreased motor coordination and impaired cognition
Benzodiazepines.docx