Antianxiety drugs. Plenopakar Blok BMS,09. Depart.Farmakologi & Terapeutik Fakultas Kedokteran USU MEDAN

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1 Antianxiety drugs Plenopakar Blok BMS,09 Depart.Farmakologi & Terapeutik Fakultas Kedokteran USU MEDAN

2 DSM IV-TR: ANXIETY - Is an emotional state,unpleasant in nature, associated with uneasiness,discomfort and concern of fear about some defined or undefined future threat. Some degree of anxiety is a part of normal life -Some psychotics and depressed patients also exhibit pathological anxiety

3 Antianxiety Drugs = mostly mild CNS depressant = aimed to control the symptoms of anxiety = produce a restful state of mind without interfering with normal mental or physical functions.

4 Antianxiety (Anxiolytics); = differ from antipsychotics; = more closely resemble sedative-hypnotics - have no therapeutic effect to control thought disorders in schizophrenia - do not produce parkinsonism - have anticonvulsant property - produce physical dependence and carry abuse liability

5 Terminologi Dulu : - anti-anxietas = anxiolitik adalah sedativa dalam dosis minimal sehingga: - efek antianxietas (+) - efek sedasi minimal - sedativa : bahan yang memiliki: - efek menenangkan dan menenteramkan - hipnotika: bahan sedativa dalam dosis lebih besar, sehingga bersifat: - menidurkan (sleep inducing) Sekarang: Buspiron: anxiolitik tanpa efek sedasi.

6 ANXIETY Psikiatri Penanggulangan : I - non pharmacologic approach II - pharmacological approach Pharmacological approach: - benzodiazepines - non benzodiazepines - buspiron - zolpidem - zaleptom - older drugs - alcohol chloralhydrate - glutethimide - meprobamate

7 Classes of sedative hypnotic drugs 1. Barbiturates - largely obsolete, though still occasionally prescribed. 2. Benzodiazepines - nowadays, the most important drugs HT 1A receptor agonists. - recently introduced, anxiolytic activity with little sedation. 4. βeta - adrenergic antagonists. - used mainly to reduce the symptoms of anxiety 5. Miscellaneous drugs.

8 BENZODIAZEPINE Masih merupakan yang terbanyak dipakai why? Gambar 1.

9 Drug Alprazolam ( Xanax R/ ). Peak blood Level (hrs) Elim. T ½ (hrs) Comments Rapid Oral abs Hp, S Chlordiazepoxid Active Met. e (Librium R/ ). erratic bioavailab.from i.m. Lp,L Diazepam (Valium R/ ). Lorazepam (Ativan R/ ) idem Hp = High - potency Lp = Low - potency S = Short Hp, half -S life L = Long half - life No active Met.

10 PHARMACODYNAMICS Mechanism of action - By binding to molecular components of the GABA receptor in CNS α or β subunits opening of Cl - Channel hyperpolarization inhibition.

11 Pharmacological Effects Efek utama BDZ adalah terhadap CNS 1. Reduction of anxiety and aggression 2. Sedation and induction of sleep. 3. Reduction of muscle tone and coordination 4. Anti convulsant effect.

12 AD. 1. Reduction of anxiety and aggression Sedation, taming effect - Tapi kadang-kadang aggression (mis. triazolam) ditarik dari peredaran di UK dll. dose-dependent anterograde amnesic effects

13 2. Sedation and induction of sleep hipnosis All hypnotic drugs : - Reduce REM sleep (BZD is the least) - hang over - irritable - Slow wave (SW) sleep juga

14 Efek sedativa hipnotika terhadap tidur Onset of sleef BZD Barb Zolp Zalep Busp Duration of NREM ( - ) REM ( - ) SW ( - ) ( - ) Zolp : Zolpidem Zalep : Zaleplon.

15 UNWANTED EFFECTS : I. Acute Toxicity - Jarang pada BDZ ok margin of safety luas tidur lebih lama. Hati-hati pada interaksi dengan - CNS depressant lain seperti alkohol, barbiturat dll. II. Side-effect pada dosis terapi : - Drowsiness Confusion -Amnesia--- retrograde amnesia--- date-rape -Gangguan koordinasi: - Driving skill - Job performance

16 III. Tolerance and Dependence - Toleransi terjadi bukan karena metabolisme seperti pada barbiturat, tapi karena terjadi perubahan pada reseptor. Dependence terjadi adalah beberapa minggu atau bulan. Withdrawal effects : Withdrawal effects : - anxiety - tremor - dizziness, nervousness - convulsions Susah menanganinya

17 Dependence, physiologic & psychologic Tergantung dari dosage, duration of therapy and potency Short acting, high- potency drugs like alprazolam or lorazepam develop sooner (in 1 or 2 months) than chlordiazepoxide Withdrawal syndrome

18 Gejala putus obat ( withdrawal syndroms) - anxiety - HR, TD - berkeringat - insomnia, - seizures - delirium tremens Pada BDZ addicts protracted withdrawal - anxiety - depression - insomnia - gangguan saluran cerna, neurologis dan otot-otot.

19 Efficacy of Pharmacologic Agents in the treatment of Anxiety disorders. Disorder BZD SSRIs TCA Bus Acute anxiety ++ Generalized anxiety D Panic disorder Social phobia Post-traumatic stress D Obsessivecompulsive D ±

20 BUSPIRONE a potent (but non-selective) agonist at 5-HT1A receptor Anxiolytic effects take days/weeks to develop Side effects : less than benzodeazepine, no sedation or loss of coordination -No tolerance or dependence -No muscle relaxant or anticonvulsant activity ending

21 β-adrenergic blockers In case there is sympathetic overactivity: -palpitation -shaking -tremor -gastrointestinal hurrying Use β-blocker

22 BZD Receptor Ligands

23 Drug Alprazolam ( Xanax R/ ). Peak blood Level (hrs) Elim. T ½ (hrs) Comments Rapid Oral abs Hp, S Chlordiazepoxid Active Met. e (Librium R/ ). erratic bioavailab.from i.m. Lp,L Diazepam (Valium R/ ). Lorazepam (Ativan R/ ) idem Hp = High - potency Lp = Low - potency S = Short Hp, half -S life L = Long half - life No active Met.