Lorazepam: Difference between revisions
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MDElliottMD (talk | contribs) parser-claude: Lorazepam MedTemplate refill, Top 300 stub upgrade |
Safety wave: 2020 FDA benzo-class boxed warning (Sept 23 2020) + propylene-glycol IV toxicity monitoring (Wilson 2005) |
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| legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids<ref name="ativan-label" /> | | legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids<ref name="ativan-label" /> | ||
| mechanism = <vote slug="lorazepam-mech-claim">Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The intermediate half-life sits between short-acting alprazolam and long-acting diazepam/clonazepam, making lorazepam a clinically versatile choice.</vote> Metabolized by '''glucuronidation rather than CYP''', so unlike alprazolam and diazepam, lorazepam has minimal CYP-mediated interactions, and the lack of active metabolites makes it the preferred benzodiazepine in elderly patients and in hepatic impairment. Tolerance, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use<ref name="ativan-label" />. | | mechanism = <vote slug="lorazepam-mech-claim">Positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and consequent neuronal inhibition. The intermediate half-life sits between short-acting alprazolam and long-acting diazepam/clonazepam, making lorazepam a clinically versatile choice.</vote> Metabolized by '''glucuronidation rather than CYP''', so unlike alprazolam and diazepam, lorazepam has minimal CYP-mediated interactions, and the lack of active metabolites makes it the preferred benzodiazepine in elderly patients and in hepatic impairment. Tolerance, dependence, and significant withdrawal syndrome on abrupt discontinuation; slow taper essential after extended use<ref name="ativan-label" />. | ||
| monitoring = '''Boxed warning:''' in September 2020 the FDA required an updated boxed warning across the benzodiazepine class for the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 23, 2020.</ref> Physical dependence can develop with continued use even at prescribed doses, and abrupt discontinuation or rapid dose reduction can precipitate acute, sometimes life-threatening withdrawal (including seizures), so prolonged use requires a gradual, individualized taper. This is in addition to the earlier boxed warning for fatal respiratory depression, coma, and death when benzodiazepines are combined with opioids or other CNS depressants.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. August 31, 2016.</ref> The intravenous formulation of lorazepam is solubilized in propylene glycol; high-dose or prolonged continuous infusion (for example in refractory status epilepticus or prolonged intensive-care sedation) can cause propylene glycol to accumulate, producing a high-anion-gap metabolic (lactic) acidosis, hyperosmolarity, and acute kidney injury. The osmolar gap and serum lactate should be monitored when large cumulative intravenous doses are given.<ref>Wilson KC, Reardon C, Theodore AC, Farber HW. Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving intravenous benzodiazepines. Chest. 2005;128(3):1674-1681.</ref> | |||
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