1 / 22

Anti-Anxiety Medications

Anti-Anxiety Medications. Brian Ladds, M.D. Anti-Anxiety Medications. 1903: first barbiturate introduced in U.S. e.g., pentobarbital (Nembutal), amobarbital (Amytal) high abuse potential, lethality in overdose & in withdrawal 1960: first benzodiazepine introduced

eliza
Download Presentation

Anti-Anxiety Medications

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. Anti-Anxiety Medications Brian Ladds, M.D.

  2. Anti-Anxiety Medications • 1903: first barbiturate introduced in U.S. • e.g., pentobarbital (Nembutal), amobarbital (Amytal) • high abuse potential, lethality in overdose & in withdrawal • 1960: first benzodiazepine introduced • e.g., chordiazepoxide (Librium), diazepam (Valium) which is more potent • now ~ 39 benzodiazepines • Other med’s are also sedative (or “anxiolytic”)

  3. Hypothesis of theNeuro-biology of Anxiety • Abnormalities in the gamma-aminobutyric acid (GABA) system • Monoamine systems are also involved • NE • SE

  4. Amino Acid Neurotransmitters • The most prevalent neurotransmitters (NT) in the brain • synthesized in the brain and well-insulated from fluctuations in serum level • Nearly all neurons: • are activated by excitatory amino acid NT • inhibited by inhibitory amino acid NT

  5. Amino Acid Neurotransmitters • Excitatory amino acid NT: • Glutamate • Inhibitory amino acid NT: • GABA • (Glycine) • Glutamate and GABA differ by a single carboxyl group

  6. Amino Acid Neurotransmitters • Actions mediated mostly at ligand-gated ion channel type receptors • rapid, short-lasting alterations in membrane potential • (In contrast to many of the receptors for DA, NE, and SE, which are G-protein coupled receptors linked to second messengers)

  7. GABA • Gamma-Amino Butyric Acid (GABA) • synthesized by glutamic acid decarboxylase (GAD) • rate-limiting step • catabolized by GABA transaminase • valproate and other medications inhibit this enzyme

  8. GABA • In the cortex, GABA is localized primarily to intrinsic neurons • local feedback loop • tonic inhibition • GABAergic dysfunction is sufficient for seizures • In extrapyramidal motor system, GABA efferent projection neurons • e.g. striato-nigral pathway: inhibit dopaminergic neurotransmission

  9. GABAA Receptor Complex • Ligand-gated chloride ion channel • brief current flow, decreasing excitability • Distinct sub-units • has a multiplicity of isoforms • >5000 possible combinations • may permit development of novel drugs that are selective

  10. GABAA Receptor Complex • 3 functional domains • GABA recognition site • ion channel site • barbiturates prolong channel opening • benzodiazepine receptor site • 1 sub-type is the “central receptor” (only in brain) • unclear endogenous ligand • benzo’s increase affinity of GABA for its binding site • inc. frequency of Cl- ion channel opening; influx of Cl- hyperpolarizes neuron, causing inhibition and decreased excitability

  11. Benzodiazepine Receptor • The benzodiazepine receptor is unique in that it mediates drugs that have opposite effects.

  12. Ligands of theBenzodiazepine Receptor • Agonists • Inverse agonists • decreases Cl- ion channel opening • anxiogenic • Antagonists • inhibit agonists and inverse agonists • restores the unmodified state • flumazenil (Mazicon) • treatment of benzo overdose

  13. Benzodiazepines • Benzodiazepines • anti-convulsants • muscle relaxants (via spinal cord) • sedative-hypnotic • anxiolytic • prevent alcohol withdrawal symptoms • e.g., Delirium Tremens “DT’s”

  14. Benzodiazepines • All BZ’s are equally efficacious • different potencies, therefore different doses • Rapid onset of action • Unlike anti-depressants • Few side effects • sedation • memory problems • dependence • withdrawal

  15. Benzodiazepines • Diazepam (Valium) • long half-life • less withdrawal • but increased sedation • Alprazolam (Xanax) • short half-life • more withdrawal • multiple daily dosing • Lorazepam (Ativan) • intermediate half-life

  16. Anxiolytics • Benzodiazepines • Barbiturates • higher lethality in overdose • Anti-depressants • Zolpidem (Ambien) • acts on the GABA receptor complex • used for insomnia • Anti-histamines • Buspirone (Buspar)

  17. Buspirone • Novel anxiolytic (for GAD) • non-sedative & non-benzodiazepine • unclear mechanism of action • may affect serotonin system in unique ways • may affect GABA system in unique ways • few side effects • no dependence or withdrawal • slow onset of action

  18. Summary: Anxiety • Low GABA ~ high anxiety (& sz. d/o) • BZ -> inc GABA ->inc Cl- -> dec excitability -> less anxiety (& sz d/o) • Other neurotransmitters (NE, SE) are also involved, and other medications are efficacious

More Related