1 / 14

Newer CNS depressants

Newer CNS depressants. Benzodiazepines, second generation anxiolytics, and antiepileptic drugs. Use of benzodiazepines. Not for chronic anxiety disorders Not for the elderly Not for depression For short-term treatment of stress-related anxiety: Acute situational grief

MikeCarlo
Download Presentation

Newer CNS depressants

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Newer CNS depressants Benzodiazepines, second generation anxiolytics, and antiepileptic drugs

  2. Use of benzodiazepines • Not for chronic anxiety disorders • Not for the elderly • Not for depression • For short-term treatment of stress-related anxiety: • Acute situational grief • Acute stress reactions • Short-term anxiety-induced insomnia

  3. Pharmacodynamics • GABAA receptor interactions • Benzodiazepine agonists, eg. diazepam • Benzodiazepine antagonists, eg. flumazenil • Chloride ion channels and fast IPSPs • GABAB receptor interactions • Presynaptic for several neurotransmitters • Potassium ion channels and late IPSPs • Baclofen, a muscle relaxant and antispastic

  4. Localized pharmacodynamics • Low-dose antianxiety effects: hippocampus and amygdala • Mental confusion and amnesia: hippocampus and cerebral cortex • Sedative-hypnotic effects: cerebral cortex • Different benzodiazepines have different relative effects, perhaps due to multiple subtypes of GABAA receptors.

  5. Pharmacokinetics • Study administration, absorption and distribution in textbook. • Metabolism is unusual: • Intermediate metabolites may be psychoactive. • Intermediate metabolites may be long-lasting. • Elderly patients have difficulty metabolizing long-acting benzodiazepines, leading to profound dementia. May take 60 days to clear.

  6. Uses and side effects of benzodiazepines • Panic attacks and phobias: alprazolam (Xanax) • Alcohol withdrawal and abstinence • Antiepileptic • Dose-related side effects: • Drug-induced brain syndrome • Impaired functioning • Amnesia • Severe interactions with alcohol

  7. Benzodiazepine miscellany • Fetal effects have been reported for BDZ taken in the first trimester, but other research disputes the claim. • If abused, BDZs are part of polydrug abuse, complicating flumazenil antagonistic effects • GABAA antagonists may enhance learning by facilitating cortical and hippocampal cholinergic activity • GABAB antagonists may enhance cognition and counter depression

  8. Second generation anxiolytics • Zolpidem (Ambien, 1993): Not a BDZ, it is a specific agonist at GABAA1 receptors. • Rapid uptake and short elimination half-life make it an effective insomnia treatment • Little interference with normal sleep cycle • Safe, and high doses trigger vomiting • High doses produce problems in older people • Flumazenil antagonizes zolpidem

  9. Second generation anxiolytics • Buspirone (BuSpar): A weak agonist of 5-HT1A receptors, so no crossing or synergy with other CNS depressants • Buspirone is also antidepressant • No sedation, little amnesia or confusion • Very slow development of main effect: several weeks tid. Minimal abuse, withdrawal symptoms. • Useful for GAD and anxiety in older people. • Postsynaptic inhibition of adenyl cyclase • Presynaptic inhibition of 5-HT synthesis • Remember grapefruit juice effect on buspirone

  10. Controversial anti-anxiety drugs • Triazolam (Halcion) • Flunitrazepam (Rohypnol) • Illegal in U.S.A. • Produces amnesia • Synergistic with alcohol: “Date-rape drug” • Roughies, roofies, rochas

  11. Future directions in anxiety control • Find partial agonists of BDZ receptors • Abecarnil, used for GAD • Find drugs which act on different receptor subtypes, like Zolpidem • Alpidem acts on GABA A1 and GABA A3 sites • Imidazenil has fewer side effects • Nonhormonal neurosteroids (epalons) as GABAA agonists: Ganaxolone • Serotonin (5HT1A) agonists, like buspirone: gepirone, alnespirone, ipsapirone

  12. Antiepileptic drugs • Epileptic seizures, foci/lesions, and kindling • Sodium channel blocking • carbamazepine, phenytoin (Dilantin) • lamotrigine, valproate/valproic acid • GABA agonism • reduce metabolism of GABA • facilitate GABA release: gabapentin • Enhance GABA action: benzodiazepines, valproic acid

  13. Other uses of antiepileptics • Kindling may be part of a set of psychiatric disorders characterized by impulse control difficulty. • Bipolar Disorder and mania • Conduct Disorder • Borderline Personality Disorder • Panic Disorder • Intermittent Explosive Disorder • Antiepileptic drugs are sometimes helpful.

  14. Antiepileptic drugs • Identify the three main groups of antiepileptic drugs. • In which group would you place carbamazepine and valproic acid? • Construct a timeline of the drug treatment of seizure disorders, starting with bromide. • How do antiepileptic drugs relate to specific psychological disorders? • http://www.pslgroup.com/dg/2d9a6.htm

More Related