🎭Anxiolytics/Hypnotics/Sedatives/Anticonvulsants.🎭 Site of action mostly is the GABA-A receptor, chloride chanells opening duration prolongation, sodium & calcium channels closure & glutamate inhibition. ✨Structure of GABA-A receptor comprises of 5 subunits. ◾ 2 α subunits (to which GABA binds) (A-GABA-A) ◾ 2 β subunits (to which *barbiturates* bind) (B-Barbiturates) ◾1 γ subunit (to which benzodiazepines bind, ( 🏹Y-BZP) • 13 known subunits of the GABA-Aγ receptor. 💥Benzodiazepine-sensitive α1, α2, α3, α5 (S 1,235) 🕳️Benzodiazepine-insensitive α4 and α6 (i46) α2, α3, and/or α5 subunits regulate anxiety, muscle relaxation, but excessive activation causes motor impairment in the limbs (dyskinesia/tremors) 💥MOA: ✓Benzodiazepines acting on α2, α3, and/or α5 subunits (but NOT α1) have demonstrated Non-sedative, non-amnesic anxiolytic properties . (235) More GABA attached to receptors • Cl- ion channel opens • Increased influx of cl- inside the cell • Cell hyperpolarized and becomes difficult for depolarization. • Decreased neuronal excitability DOA; ✨Short acting: Oxazepam Triazolam 🌟Intermediate acting: •Alprazolam •Estazolam •Lorazepam •Temazepam •Bromazepam •Loprazolam •Lormetazolam 💫Long acting: Duration of action is 1-3 days •Clorazepate •Chlordiazepoxide •Diazepam •Flurazepam •Quazepam •Nitrazepam 🌟 Actions: Reduction in anxiety Sedative and hypnotics action Anticonvulsant Muscle relaxant Immune suppression 🌟Indications: Panic disorder, GAD, Performance anxiety OCD, PTSD, Phobic anxiety Insomnia alcohol withdrawal transplant rejection Anesthesia aid Seizures Epilepsy 💦Adverse effects: Drowsiness confusion Agitation Ataxia Tardive dyskinesia Cognitive impairment Amnesia Delirium Physical Dependency Reversible effects: In most cases, memory issues related to benzodiazepine use tend to improve once the medication is discontinued. However; worsening Alzheimer's or pre-existing memory/attention problems. 💉🚷BDZ, antagonist Flumazenil (GABA receptor antagonist) that's given in against to BZP toxicity related s/s i.e Other anxiolytics 💥Buspirone 🌟Uses GAD 🌟S/E hypothermia, inc. Gh and prolactin, headache, dizziness. 💥Hydroxyzine; H1 B, anti-emetic. 🌟Uses; Used in anxiety with history of drug abuse. & For sedation prior to dental surger 🌟Addiction Since Hydroxyzine is not a habit-forming drug, the recovery rate for people addicted to this drug is considerably higher than other drug 🌟Withdrawal symptoms start within 6 to 12 hours after the last dose and may last from days to several weeks. 🍂🍂🍂🍂🍂🍂🍂🍂🍂 Barbiturates First ever anxiolytics, hypnotics, sedatives, & antiepileptics. Now replaced by BZPs due to their adverse effects. Narrow therapeutic index & the therapeutic dose is closed to toxicity. Phenobarbital the longest acting (1-2 days) while Thiopental is the shortest acting (20 minutes) 🌀Duration of action 🌟Long acting: Phenobarbital: 1-2 days 🌟Short acting: Pentobarbital Secobarbital Amobarbital Duration of action: 3-8 hours 🌟Ultra short acting: Thiopental: 20 minute 💫Therapeutic uses • Anesthesia:(induction) ultra short acting such as *thiopental/thiopentone* IV 3-4mg/kg. • Anticonvulsant: such as *phenobarbital* is used in tonic-clonic seizures, status epilepticus (epilepsy) and eclampsia (pregnancy) • Anxiety • High ICP • Insomnia 🌟Side effects • Drowsiness • Impaired concentration • Mental and physical sluggishness • Drug hangover • Physical dependence • Poisioning 🥱😶‍🌫️Other Sedatives (unconsciousness) & hypnotics (sleep inducing) ◾Zolpidem: Has a high affinity to α1-GABA-A receptors, an intermediate affinity to α2- and α3-GABA-A receptors and fails to bind to α5-GABA-A receptors. it doesn't have any active metabolite, effect lasts upto next day. No anticonvulsant or muscles relaxant effects on low doses like barbiturates & BZPs do. Suitable for sleep induction or short term insomnia. It should be used only for 7-10 days (not more, can cause dementia, headache, depression, drug dependency, dizziness) ◾Zaleplon: similar to zolpidem ◾ Eszopiclon 🪻Ramelton: Selective agonist at MT1 and MT2 subtypes of melatonin receptors. Stimulation of these receptors in *supra-chiasmatic nucleus* by melatonin promotes sleep and maintain circadian rhythm. Tasimeltion Orally active for non24h sleep 🍭Chloral hydrate: Is a tri-chlorinated derivative of *acetaldehyde* that is converted to the active metabolite, Tri-chloro-ethanol in the body. Induce sleep in about 30 minutes and lasts for approximately 6 hours. PO, 700 mg OD Uses; Insomnia, nausea, labyrinthine disorders, vertigo, preoperative & post operative sedation. 🚷 Assessment Under the 1986 cancer guidelines (U.S. EPA, 1986), chloral hydrate is assigned to Group C, possible human carcinogen. Side effects; Produces gastric distress, liver cirrhosis, hepatic coma, bradycardia, respiratory depression. Orexin receptor antagonists. (Orexin is a chemical that keeps one awake, works like serotonin, the opposite of melatonin) ◾Suvorexant; 10-20 mg/ QD, PO Difficulty falling & staying asleep. 5HT1A receptor agonist ◾Buspirone 10 mg/d po. 5HT1A & D2. •Anxeity • Depression •GAD. Side effects; nausea vomiting, gastritis, dizziness. 🌴🌴🌴🌴🌴🌴🌴🌴🌴 ‎Follow the 🩺Khyber Medical University Peshawar SaMiii-KMU 🧑‍⚕️ channel on WhatsApp: https://whatsapp.com/channel/0029VaDLZ5U8fewk2H3OPb0n