pharma fouda 3_p103-104.pdf

Part 3: Sedative-Hypnotic Drugs  These are drugs that cause sedation and relieve anxiety (anxiolytics), or can induce sleep. They are used primarily to treat anxiety and insomnia.  Because there is considerable chemical variation within the group, these drugs are classified based on...

Part 3: Sedative-Hypnotic Drugs  These are drugs that cause sedation and relieve anxiety (anxiolytics), or can induce sleep. They are used primarily to treat anxiety and insomnia.  Because there is considerable chemical variation within the group, these drugs are classified based on their clinical uses rather than on chemical structure. Drugs with main use as sedatives: Drugs with main use as hypnotics:  Benzodiazepines  Barbiturates  Buspirone  Ramelteon  Chloral hydrate 1. Benzodiazepines  Benzodiazepines (BDZ) have a great margin of safety over previously available sedative–hypnotic agents (e.g., barbiturates).  Most benzodiazepines have qualitatively similar therapeutic actions but differ in their relative lipid solubility, metabolism, and elimination half-life. Classification Short acting (t½ < 5h): midazolam – triazolam Intermediate acting (t½ 5-24 h): alprazolam – lorazepam - clonazepam Long acting (t½ > 24 h): diazepam – clorazepate - flurazepam Pharmacokinetics – Oral absorption is good and rapid. Highly lipid soluble drugs (e.g., midazolam, triazolam) have fast onset of action. – Long acting drugs are metabolized by oxidation (CYP450) into active metabolites giving them long duration of action (e.g. diazepam). – Short acting drugs are metabolized by conjugation into inactive metabolites followed by renal clearance. – In a patient with liver dysfunction, lorazepam and oxazepam, which are metabo- lized extrahepatically, are less likely to cause excessive CNS depression. Mechanism of action  BDZ have special receptors in the CNS and peripheral tissue.  By acting on these receptors, BDZ cause allosteric modulation of GABA action on GABAA receptors resulting in ↑ Cl- conductance and hyperpolarization.  Six BDZ receptor subtypes have been discovered; subtype 1 is the most widely expressed and mediates most of the effects of BDZ. 339  Pharm macologica al effects  Redduction off anxiety (anxiolytic ( effect) in smaall dose producing p calming effect in mann & tamingg effect in animals a  Hyp ect: in high pnotic effe her doses.  Cenntral skele etal musc cle relaxattion: this is u useful sinc ce increas sed ms to one is a commmon feature in anx xiety and mmay lead to h headache and a ms pa ain.  Antticonvulsa ant effect.  Acuute amnes sia: after high doses.. peutic use Therap es Anx xiety disorrders: e.g.. – A Acute anxiety. – G Generalizeed anxiety disorders (GAD). – S Social phoobia (social anxiety d disorder). BDZ Z are effec ctive for th he short-tterm mana agement (