The onset of action after an IV dose is 1-5 minutes. Diazepam is widely distributed, with CSF levels similar to plasma levels. These metabolites are subsequently glucuronidated and excreted in the urine. Diazepam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected, or a history of substance abuse. Abrupt discontinuation of diazepam after prolonged use can cause seizures in susceptible patients.
Benzodiazepine withdrawal causes irritability, nervousness, and insomnia.
Benzodiazepine withdrawal is more likely to occur following abrupt cessation after excessive or prolonged doses, but it can occur following the discontinuance of therapeutic doses administered for as few as 1-2 weeks. Benzodiazepine withdrawal is also more severe if the agent involved has a relative shorter duration of action. Abdominal cramps, confusion, depression, perceptual disturbances, sweating, nausea, vomiting, parasthesias, photophobia, hyperacusis, tachycardia, and trembling also occur during benzodiazepine withdrawal, but their incidence is less frequent. Convulsions, hallucinations, delirium, and paranoia also can occur. Benzodiazepines should be withdrawn cautiously and gradually, using a very gradual dosage-tapering schedule.