Benzodiazepines Lorazepam → Benzodiazepine (indirect agonist) → GABA ↑ Cl- channel opening → hyperpolarisation of post-synaptic neurons → Cl- frequency ↑ → neuron excitability → duration of N3 Phase of NREM Sleep ↓ → night walk? → nightmares Effects anxiolysis sedation hypnotic actions m. relaxant anti-convulsant action amnesia → partial or complete memory loss → inability to form new memories may be desired in the pre-operative setting Indications Anxiety → lorazepam Insomnia → flurazepam Alcohol withdrawal → diazepam, lorazepam Seizures / status epilepticus → Perioperative / post-operative sedation → Others → m. spasm, catalonia, eclampsia, sleepwalk, nightmares ADRs anterograde amnesia confusion blunted affect residual sedation → persist beyond desired timeframe coordination ↓ injury risk ↑ paradoxical rxn to benzos restlessness, irritability, impulsivity, disinhibition risk groups = children & older adults with a history of substance use disorder or another psychiatric condition Rx = discontinue drug Risks of overdose: when combined with other CNS depressants (e.g. alcohol, opioids, barbiturates, anti-histamines) → not as life threatening respiratory depression Rebound phenomenon is reemergence of symptoms e.g. depression, insomnia & anxiety upon discontinuation of benzodiazepine therapy often with ↑ intensity esp. common in Rx of sleep disorders Other Notes tolerance & withdrawal → short acting drugs are associated with a higher dependence risk risk of developing substance use disorder interactions = Cytochrome P450 induction Benzodiazepine Dependence physical adaption to sustained use of substance with the development of tolerance & withdrawal Clinical features: ANS Neurological Psychiatric * diaphoresis * Seizures * Anxiety * nausea & vomit * Tremors * Depressed mood * anorexia * Memory impairment * Insomnia * ↑ HR * Withdrawal psychosis with transient optic, auditory or tactile hallucinations * ↑ HTN