PHTH1011 009 Sedatives and Hypnotics - Williams.pdf

Sedative-Hypnotics & General Anaesthetics Prof Maxine Gossell-Williams Dept. of Basic Medical Sciences Pharmacology & Pharmacy Section Email: [email protected] Definitions Sedative (anxiolytic): reduces anxiety, moderates excitement, exerts a calming effect with no effect on motor or men...

Sedative-Hypnotics & General Anaesthetics Prof Maxine Gossell-Williams Dept. of Basic Medical Sciences Pharmacology & Pharmacy Section Email: [email protected] Definitions Sedative (anxiolytic): reduces anxiety, moderates excitement, exerts a calming effect with no effect on motor or mental function Hypnotic: produces drowsiness and facilitates the onset and maintenance of sleep. It also allows for easy arousal from sleep General Anaesthetics: agents that produce a reversible state of unconsciousness to allow for the performing of surgical procedures. The Sleeeeeeeeeeep cycle Made up of Non-REM and REM (Rapid Eye Movement) patterns (based on brainwave amplitudes and frequencies) One complete sleep cycle lasts about 90 to 100 mins An average sleep period4 to 5 complete sleep cycles. https://www.catalystathletics.com/article/1845/Understanding-Sleepfor-Optimal-Recovery-Productivity/ https://www.youtube.com/watch?v=P7BR5rwUbak&t=4s DIAZEPAM MOA: Binds to and modulates the GABA type A receptor to potentiate the activity of GABA CLINICAL APPLICATIONS ANXIOLYTIC (SEDATIVE) HYPNOTIC ANEASTHESIA MUSCLE RELAXATION ANTICONVULSANTS EFFECTS ON SLEEP Decrease sleep latency Increase in total sleep time Increase NREM, decrease REM DIAZEPAM –Absorption/ Distribution Generally given orally- Well absorbed Given parenterally for seizures and when used in anaesthesia Very lipid soluble, quick entry into the CNS- quick onset. Termination with redistribution to peripheral sites Show multi-compartment model of elimination The more overweight -longer retention in body high plasma protein binding DIAZEPAM –Metabolism/Elimination Undergoes PHASE I (oxidation) to produce OXAZEPAM (active metabolite) and then PHASE II (glucoronylated) via hepatic microsomal enzymes S/E Therapeutic doses: anterograde amnesia (inability to form long-term memories) Rebound increase in REM with discontinuation Overdose =pro-longed sleep Tolerance/dependence Flumazenil: Antagonists of Benzodiazepine receptor. GENERAL ANAESTHETICS INHALANTS: ISOFLURANE NITROUS OXIDE INTRAVENOUS AGENTS: PROPOFOL PROPOFOL Potentiate the activity of GABA on the GABA-Type A channel. IV Agent used to induce anaeasthesia Onset = within 40 seconds from the start of an injection Then GA maintained with inhalants Metabolised in liver and eliminated renally ISOFLURANE Volatile liquid, vapourized and inhaled and once in the CNS– Induce unconsciousness. Once inhaled-partition between blood and gas: Less soluble in blood and tissues, faster accumulation in CNS= quicker induction. Onset is not as rapid as IV agents. Agents are excellent for maintenance Removed rapidly from the body via the lungs once administration has terminated does not irritate the airways and therefore safe in asthmatics Does NOT produce analgesia and muscle relaxation NITROUS OXIDE Does NOT produce unconciousness Mixed with oxygen and used as a carrier for isoflurane Produces significant analgesia and muscle relaxation SUPPLEMENTARY DRUGSPREMEDICANTS/POSTMEDICANTS Sedative/hypnotics : e.g. diazepam Muscle relaxants: e.g. succinylcholine Analgesics: e.g. Morphine, Fentanyl Anti-emetics – Metoclopramide