MC - Anxiolytics, Hypnotics and Barbiturates PDF

ANXIOLYTICS, HYPNOTICS AND BARBITURATES Sonia Guadalupe Barreno Rocha MD, PhD [email protected] WE MAKE DOCTORS Let’s talk about anxiety and sleep disorders ANXIETY DISORDERS Anxiety is normally an adaptive response that prepares a person to rea...

ANXIOLYTICS, HYPNOTICS AND BARBITURATES Sonia Guadalupe Barreno Rocha MD, PhD [email protected] WE MAKE DOCTORS Let’s talk about anxiety and sleep disorders ANXIETY DISORDERS Anxiety is normally an adaptive response that prepares a person to react to the challenges of life. Anxiety is characterized by: Changes in mood Sympathetic Hypervigilance (apprehension nervous system and fear) arousal Stevens CW. Brenner and Stevens' Pharmacology. 2023.  When anxiety becomes chronic, it can impair a person’s ability to perform the activities of daily living. Patients with chronic anxiety may develop: Gastroinstestinal Cardiovascular Neurologic Sweating problems (diarrea) problems problems (Tremor, (tachycardia) dizziness) Lead to Self-medication Substance abuse Stevens CW. Brenner and Stevens' Pharmacology. 2023. Classification and Treatment of Anxiety Disorders The appropriate management of anxiety disorders requires an accurate diagnosis, and treatment may involve the use of pharmacologic agents, psychotherapy, or both. Stevens CW. Brenner and Stevens' Pharmacology. 2023. Overview of the most important anxiety disorders Obsessive- Post-Traumatic Substance/Me Generalized Compulsive Stress Disorder dication- Characteris Social anxiety Specific Disorder (PTSD) Induced Acute anxiety anxiety Panic disorder Agoraphobia tics disorder phobias (OCD) Anxiety disorder (GAD) Disorder Ego-dystonic Psychatric Prominent Pronounced Obsessions disorder triggered anxiety or panic Peak with Pronounced fear Persistent fear or anxiet Compulsions by a personally attacks after several minutes Excessive and and/or anxiety of and intense y of Recurrent experienced or using or Clinical and involve ≥ 4 persistent social situations fears of situations unexpected pa witnessed stopping a features cognitive and/or anxiety and/or that involve particular that are nic attacks traumatic event substance/medi somatic fear scrutiny from situations or perceived as cation symptoms others objects difficult to escape from Situation or Traumatic events, Alcohol Being in environment sexual or physical Caffeine Illness, Social interaction One or enclosed that causes violence, natural Corticosteroids separation from May not have and/or more spaces or stress disasters, war, Amphetamines, loved ones, or No definitive Triggers an obvious performance of specific open public diagnosis of cannabis the anticipation trigger or source trigger any actions in situations or spaces severe disease, of stressful public objects Crowds witnessing the events Being alone death, accidents Panic attacks: Undetermined More than a Within 1 several month month of using Duration of ≥ 6 or stopping the minutes symptoms Few weeks to a months in ≥ substance/medi ≥ 6 months Fear of ≥ 6 months ≥ 6 months required for few months 2 different cation subsequent diagnosis situations attacks: ≥ 1 month CBT First-line: Discontinuation Acute panic First SSRIs psychotherapy of the Benzodiazepin attack: short- SSRIs or SNRIs an line: SSRIs or SN CBT (desen (trauma-focused substance/medi e might provide acting benzodi d/or CBT RIs and/or CBT sitization CBT, EMDR) with cation Treatment short-term relief azepines Performance- Alternatives: bus therapy) CBT or without CBT of anxiety from more Long- only social anxiety pirone, applied Benzodiaze SSRIs pharmaco SSRIs or SNRIs disorders severe acute term manage disorder: CBT and relaxation pine or SSRI Pharmacotherapy anxiety ment: SSRIs or /or propranolol or therapy, biofeed s : SSRIs, SNRIs, conditions. SNRIs and/or C clonazepam back prazosin, benzos BT SLEEP DISORDERS Reversible state of reduced consciousness accompanied by characteristic changes in the electroencephalogram (EEG). Stevens CW. Brenner and Stevens' Pharmacology. 2023. Classification and Treatment of Sleep Disorders Insomnia Difficulty to go to sleep or to stay asleep during the night, whereas others awaken too early in the morning. The management of insomnia depends on whether the sleep disorder is caused by physiologic, psychologic, or medical conditions. Severe insomnia caused by medical conditions is treated with benzodiazepines or other sedative-hypnotic drugs Insomnia related to psychological and psychiatric disturbances is best managed with a combination of psychotherapy and sedative-hypnotic drugs. Stevens CW. Brenner and Stevens' Pharmacology. 2023.  Hypersomnia Other sleep disorders Narcolepsy Most of these disorders are managed with a combination Enuresis of psychotherapy and antidepressant drugs or CNS Somnambulism stimulants. Sleep apnea Nightmares and night terrors Stevens CW. Brenner and Stevens' Pharmacology. 2023. Basic Pharmacology of Sedative-Hyptonics  An effective sedative A hypnotic drug should (anxiolytic) agent produce drowsiness should reduce anxiety and encourage the and exert a calming onset and maintenance effect. of a state of sleep. Sedative-hypnotics (like barbiturates) may depress respiratory and vasomotor centers in the medulla, leading to coma and death. Vanderah TW. Katzung’s Basic & Clinical Pharmacology. 2024. BENZODIAZEPINES Oxaz epam Alpra Midaz zola olam m Fa There are so many Clona mil Loraz more, this are just some of them zepa m y epam Triazo Diaze lam pam Vanderah TW. Katzung’s Basic & Clinical Pharmacology. 2024. Mechanism of action Binds in the chloride ion channel between α1 and γ subunits increasing the affinity of GABA and increasing the frequency with which the channel opens. The benzodiazepines exert their effects on sleep and consciousness by facilitating the activity of GABA at various sites in the brain. Stevens CW. Brenner and Stevens' Pharmacology. 2023. Vanderah TW. Katzung’s Basic & Clinical Pharmacology. 2024. ADME Oxazepam Diazepam Lorazepam Drug presentation Oral Oral, IV, IM, rectal Oral, IV, IM,SC, rectal Anticonvulsant: IV: Within 10 minutes Status epilepticus: IV: 1 to 3 minutes; Onset of action 30-60 minutes Hypnosis: IM: 20 to 30 minutes Rectal: 2 to 10 minutes Sedation: IV: Within 2 to 3 minutes Pediatrics: 60-120 min Anesthesia premedication: IM, IV: ~6 to Duration of effect 6 to 8 hours Status epilepticus: 15-30 min 8 hours Slowly absorbed from the GI Well absorbed, active metabolite IM: Rapid and complete absorption; Absorption tract (clorazepate) is more rapidly absorbed Oral: Readily absorbed Protein binding 96% to 98% 95% to 98% ~91% Hepatic glucuronide Hepatic, N-demethylated by CYP3A4 conjugation to produce a Hepatic; rapidly conjugated to Metabolism and CYP2C19 to the active metabolite inactive metabolite lorazepam glucuronide (inactive) N-desmethyldiazepam (benzophenone) Half-life ~33 to 72 hours; Desmethyldiazepam: Oral: ~12 hours; IV: ~14 hours; IM: ~13 to elimination ~8 hours (range: 6 to 11 hours) ~71 to 174 hours 18 hours; End-stage renal disease (adults) (depending on the presentation) (ESRD): ~18 hours Urine (as inactive glucuronide Urine (as inactive glucuronide Urine (~88%; predominantly as inactive Excretion conjugate) conjugate) metabolites); feces (~7%) ADME Alprazolam Clonazepam Triazolam Midazolam Drug Oral Oral Oral IM, IV, oral, nasal, buccal, rectal presentation IM: Sedation: Adults: ~15 minutes; Infants and young Onset of IV: 3-5 minutes; Oral: 10-20 30-60 minutes children: 6 to 8 hours; Hypnotic: 15 to 30 minutes action minutes; Intranasal: Within 10 Adults: ≤12 hours minutes IM: Up to 6 hours; Mean: 2 hours; Duration of ~6 hours 8 to 12 hours Hypnotic: 6 to 7 hours IV: Single dose: