Pharmacology of Anxiolytic/ Sedative-HypnoticsAbstractObjectivesAnxietyAnxiety SymptomsIndications for Antianxiety/Sedative-HypnoticsGADPhobic DisordersPsychological Factors Affecting Medical ConditionPanic DisorderSymptomatology of Panic AttacksCourse of IllnessObsessive-Compulsive Disorder (OCD)Obsessions in OCDCompulsive Behaviors in OCDPosttraumatic Stress Disorder (PTSD)Sleep DisordersPharmacodynamicsGABA 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: BuspironeTreatment Strategy for GADSlide 39Slide 40Treatment Strategy for PHOBIC DisordersSlide 42Slide 43Treatment Strategy for PANIC Disorder with or without AgoraphobiaSlide 45Slide 46Slide 47Slide 48Slide 49Treatment Strategy for OBSESSIVE-COMPULSIVE and Related DisordersSlide 51Slide 52Slide 53Slide 54Treatment Strategy for SLEEP DisordersSlide 56Slide 57Slide 58ANTIANXIETY AGENTSSEDATIVE-HYPNOTICSReferences01/13/19 1Pharmacology of Anxiolytic/ Sedative-HypnoticsPhilip G. Janicak, MDProfessor of Psychiatry and PharmacologyUniversity of Illinois at Chicago01/13/19 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-hypnotics01/13/19 3pharmacology of anxiolytic/sedative-hypnoticsObjectivesReview diagnostic indications for anxiolytic/ sedative-hypnoticsReview different classes of antianxiety and sedative-hypnotic agents in terms of their pharmacodynamics; pharmacokinetics; adverse effects; and potential for drug interactions.Review treatment strategies for anxiety and sleep disorders.01/13/19 4pharmacology of anxiolytic/sedative-hypnoticsAnxietyNatural human experienceSubjective qualities of fear or related emotionsEnsures survival and adaptationIn excess, can cripple and destroy01/13/19 5pharmacology of anxiolytic/sedative-hypnoticsAnxiety SymptomsAnxiety symptoms are associated with numerous medical conditions:Cardiovascular diseaseEndocrine diseaseGastrointestinal diseaseNeurologic diseaseDrug-induced01/13/19 6pharmacology of anxiolytic/sedative-hypnoticsIndications for Antianxiety/Sedative-HypnoticsGeneralized anxiety disorder (GAD)Phobic disordersPsychological factors affecting medical conditionPanic disorderObsessive-compulsive disorderPosttraumatic stress disorderSleep disorders (dyssomnias; parasomnias)01/13/19 7pharmacology of anxiolytic/sedative-hypnoticsGADRepresents up to 50% of anxious patients seen by physiciansIncreased annual medical expensesOften unnecessary medical consultations 55 million prescriptions for BZDs in 1989Anxiolytic agents fourth most prescribed class of medication01/13/19 8Phobic DisordersDisabling anxiety (at times associated with panic attacks) and avoidanceAgoraphobiaSocial phobia (Social Anxiety Disorder)Specific phobiapharmacology of anxiolytic/sedative-hypnotics01/13/19 9Psychological FactorsAffecting Medical ConditionPsychologically meaningful environmental stimuliTemporally related to the initiation or exacerbation of a physical conditionDemonstrable organic pathology (e.g., rheumatoid arthritis)Known physiological process (e.g., migraine)pharmacology of anxiolytic/sedative-hypnotics01/13/19 10pharmacology of anxiolytic/sedative-hypnoticsPanic DisorderSudden, spontaneous, unexpected feelings of terror and anxietyThe autonomic equivalence of anxietyThe desire to flee the situation and return to a safe placeA phobic avoidance of the places where such attacks occur01/13/19 11Symptomatology of Panic AttacksShortness of breath /smothering sensationsDizziness, unsteady feelings, or faintnessPalpitations/tachycardiaTrembling/shakingSweatingChokingNausea/abdominal distressDepresonalization/ derealizationParesthesiasFlushes/chillsChest pain or discomfortFear of dyingFear of going crazy or doing something uncontrolled pharmacology of anxiolytic/sedative-hypnotics01/13/19 12Course of IllnessPanicGADNormalanxiety leveltimepharmacology of anxiolytic/sedative-hypnotics01/13/19 13pharmacology of anxiolytic/sedative-hypnoticsObsessive-Compulsive Disorder (OCD)Recurrent obsessions and/or compulsions:Cause marked distress, are time-consuming, or interfere with functioningAre recognized as excessive or unreasonableAre not due to the effect of a substance or general medical condition01/13/19 14pharmacology of anxiolytic/sedative-hypnoticsObsessions in OCDContaminationPathological doubtAggressive impulsesSomatic concernsNeed for symmetrySexual impulses01/13/19 15pharmacology of anxiolytic/sedative-hypnoticsCompulsive Behaviors in OCDCleaningWashingCheckingExcessive ordering/arrangingCountingRepeatingCollecting01/13/19 16Posttraumatic Stress Disorder (PTSD)Due to an unusual experience that would be very stressful for almost anyone (e.g., combat, rape, sudden unexpected death of a loved one)Symptoms include:Intrusive recollections; frightening dreams; sense of event recurringIntensive physiological stress; hyperarousalEmotional numbingPersistent avoidance of stimuli associated with the traumaHigh comorbidity with other psychiatric disordersIncrease suicide attempt riskFemale-to-male lifetime prevalence ratio of