Pharmacology of Anxiolytic/ Sedative-HypnoticsAbstractObjectivesAnxietyAnxiety SymptomsLifetime And 12-Month Prevalence Of Anxiety Disorders In The NCSANTIANXIETY AGENTSSEDATIVE-HYPNOTICSPharmacodynamicsGABA Function and DistributionGABAA-BZD Supramolecular ComplexGABAA Receptor Structurepharmacology of anxiolytic/sedative-hypnoticsBZD ReceptorsBZD Receptor ActivityNon-Benzodiazepine AgentsNon-Benzodiazepine Agents (con’t)Serotonin ModelSerotonin ReceptorsSerotonin Agents: Indications for Anxiety-Related DisordersNoradrenergic ModelNorepinephrine ReceptorsPharmacokinetics: BenzodiazepinesDrug Interactions: BenzodiazepinesAdverse Effects: BenzodiazepinesAbuse, Dependence, Withdrawal, and Rebound Anxiety: BenzodiazepinesPharmacokinetics/Pharmacodynamics: BuspironeAdverse Effects: BuspironeIndications for Antianxiety/Sedative-HypnoticsGADTreatment Strategy for GADSlide 32Slide 33Phobic DisordersTreatment Strategy for PHOBIC DisordersSlide 36Slide 37Anxiety Disorder due to General Medical ConditionPanic DisorderSymptomatology of Panic AttacksTreatment Strategy for PANIC Disorder with or without AgoraphobiaSlide 42Slide 43Slide 44Slide 45Slide 46Obsessive-Compulsive Disorder (OCD)Obsessions in OCDCompulsive Behaviors in OCDTreatment Strategy for OBSESSIVE-COMPULSIVE and Related DisordersSlide 51Slide 52Slide 53Slide 54Posttraumatic Stress Disorder (PTSD)Slide 56Slide 57Sleep DisordersTreatment Strategy for SLEEP DisordersSlide 60Slide 61Slide 62References01/15/19 1Pharmacology of Anxiolytic/ Sedative-HypnoticsPhilip G. Janicak, MDProfessor of Psychiatry and PharmacologyUniversity of Illinois at Chicago01/15/19 2AbstractRecent anxiolytic and sedative-hypnotic agents offer comparable efficacy, fewer serious adverse effects, and less risk of a fatal consequence due to accidental or intentional overdose in comparison to alcohol, barbiturates and other non-barbiturate agents (e.g., meprobamate). Unfortunately, they have not entirely eliminated the hazards of tolerance, dependency, and withdrawal syndromes, although they have a lower abuse potential than their predecessors.For these reasons, it is important to become knowledgeable about the basic pharmacology of these drugs, in addition to their appropriate clinical indications, dosages, and duration of usage. Most importantly, their limitations must receive as much attention as their assets.pharmacology of anxiolytic/sedative-hypnotics01/15/19 3pharmacology of anxiolytic/sedative-hypnoticsObjectivesReview different classes of antianxiety and sedative-hypnotic agents in terms of their pharmacodynamics; pharmacokinetics; adverse effects; and potential for drug interactionsReview diagnostic indications for anxiolytic/ sedative-hypnoticsReview treatment strategies for anxiety and sleep disorders01/15/19 4pharmacology of anxiolytic/sedative-hypnoticsAnxietyNatural human experienceSubjective qualities of fear or related emotionsEnsures survival and adaptationIn excess, can cripple and destroySubjective, physiological, behavioral aspects01/15/19 5pharmacology of anxiolytic/sedative-hypnoticsAnxiety SymptomsAnxiety symptoms are associated with numerous medical conditions:Cardiovascular diseaseEndocrine diseaseGastrointestinal diseaseNeurologic diseaseDrug-induced01/15/19 6Kessler et al. Arch Gen Psychiatry. 1994;51:8.Anxiety Disorders Lifetime (%) 12-Month (%)Panic Disorder 3.5 2.3Agoraphobia without panic 5.3 2.6Social Phobia 13.3 7.9Simple Phobia 11.3 8.8Generalized Anxiety 5.1 3.1DisorderPosttraumatic Stress 7.6 3.9DisorderAny anxiety disorder 28.7 19.3Lifetime And 12-Month Prevalence Of Anxiety Disorders In The NCS01/15/19 7Generic Names Trade Names Daily Dosage (mg/day)BENZODIAZEPINESChlordiazepoxide Librium, others 10-100Diazepam Valium, others 2-40Oxazepam Serax, others 30-120Chlorazepate Tranxene, others 15-60Lorazepam Ativan 1-10Prazepam Centrax 20-60Halazepam Paxipam 60-160Alprazolam Xanax 0.75-4AZAPIRONESBuspirone Buspar 15-60ANTIDEPRESSANTSSSRI Sertraline, others 25-250Venlafaxine Effexor 75-375ANTIANXIETY AGENTS01/15/19 8Generic Names Trade Names Daily Dosage (mg /day)BENZODIAZEPINESLong-actingFlurazepam Dalmane 15-45Quazepam Doral 7.5-15Intermediate-actingEstazolam Prosom 0.5-2Temazepam Restoril 15-45Short-actingTriazolam Halcion 0.125-0.25NONBENZODIAZEPINE Zolpidem Ambien 5-20Zaleplon Sonata 5-20SEDATING ANTIDEPRESSANTSTrazodone Dyserel 25-100BARBITURATE-LIKEChloral Hydrate Notec 500-1500OTHERMelatonin 0.3-2SEDATIVE-HYPNOTICS01/15/19 9pharmacology of anxiolytic/sedative-hypnoticsPharmacodynamicsBenzodiazepinesSpecific binding site associated with GABAA receptor-chloride ion channelPotentiate GABA Serotonergic effects (e.g., clonazepam)Azapirone (e.g., buspirone)5-HT1A agonist: acutely, firing, in dorsal raphe nuclei; chronically, receptor desensitization activityBeta-blockers receptors central and peripheral, post synapticClonidineAgonist at 2 receptors, central, pre-synapticAntidepressants01/15/19 10pharmacology of anxiolytic/sedative-hypnoticsGABA Function and DistributionInhibitory neurotransmitterWidely distributed throughout CNSLocal inhibitory action, therefore rapidly alters neuronal outputDesensitization to inhibitory effects with chronic stimulation of GABA11 01/15/19GABAA-BZD Supramolecular Complex01/15/19 12S.M. Paul, 1995GABAA Receptor StructureBenzodiazepinesAgonistsAntagonists-Inverse AgonistsDBI PeptidesConvulsantsPicrotoxinTBPSCl-GABA AgonistsMuscimolGABA AntagonistsBicucullineBarbituratesNeuroactive SteroidsAlcoholsAnesthetics01/15/19 13GABAA receptorCytoplasmBenzodiazepine-binding domainpharmacology of anxiolytic/sedative-hypnotics01/15/19 14BZD ReceptorsType IPredominates in cerebellumAnxiolytic propertiesLess sedative propertiesType IILocated in cortex, hippocampus, spinal cordNo anxiolytic propertiesSedative propertiesType IIILocated in peripheral tissueNo anxiolytic properties? other propertiespharmacology of anxiolytic/sedative-hypnotics01/15/19 15BZD Receptor ActivityFull AgonistPartialAgonistAntagonistPartial InverseAgonistFull InverseAgonistAnxiolyticSed-HypnoticMyorelaxantAnticonvulsantAmnesticDependencyAnxiolytic No clinicaleffectPromnesticAnxiogenicPro-convulsantPromnesticAnxiogenicPro-convulsantpharmacology of anxiolytic/sedative-hypnotics01/15/19 16Non-Benzodiazepine AgentsImidazopyridines (e.g., zolpidem,
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