DH206 Pharmacology Chapter 11: Antianxiety Agents Lisa Mayo, RDH, BSDH Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Antianxiety Agent Outline Definition Mechanism of Action Benzodiazepines Barbiturates Other sedative/hypnotic drugs Centrally acting muscle relaxants

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Definitions

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Definitions Sedative-hypnotic agents produce varying degrees of CNS depression (depending on dose) Small dose: sedation (reduction of activity and simple anxiety) Larger dose of the same drug: hypnotic dose (sleeping) Even larger doses: anesthesia or death

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Action ADME

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Mechanism of Action Activity of brain dependent on action of NTs that can either stimulate or inhibit activity Inhibiting neurotransmitter in CNS = GABA (Gamma- aminobutyric acid) When GABA released, binds to own receptors located on neuron membranes Action: ↑ influx Cl ions which will reduce action potentials & keep cell in HYPERPOLARIZED state 50% of inhibition of brain/spinal column “Lady GABA doesn’t excite me!”

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ADME Most anti-anxiety drugs are highly lipid soluble Oral, Parental forms Long ½ life’s Stored in adipose tissues Highly PRO-Bound Phase I & II metabolism Pregnancy category X Addiction & Tolerance

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Benzodiazepine’s

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Benzodiazepines Drug of choice for short-term tx of anxiety disorders Do NOT use more than 2-6mo – dependency, tolerance will develop quickly Long-term tx anxiety/depression: anti-psychotics (CH17) Drugs end in ~lam & ~pam Wide margin of safety: less likely to OD Tx OD with antagonist: flumazenil (Romazicon) Benzo antagonist

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Benzodiazepines Uses of Benzo’s Anxiolytic (relief of anxiety) Sedative Hypnotic (induce sleep) Muscle relaxant Anticonvulsant – CH16 Alcohol withdrawal Conscious sedation in dentistry or pre-op anti-anxiety agent (Remember from CH10) ALL NBQ INFO!

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Benzodiazepines USE THIS TABLE FOR DRUGS TO KNOW, NOT TABLE 11-1, P.125 BenzodiazepinesUses Alprazolam(Xanax)Used for anxiety reduction in dental office CANNOT use grapefruit juice (NBQ) Lorazepam(Ativan)Used for anxiety reduction in dental office Triazolam(Halcinon)Used in anxiety reduction in dental office Clonazepam(Klonopin)Also used as anti-seizure Diazepam(Valium)Used in dentistry for oral or IV sedation Very long half-life Midazolam(Versed)Used in dentistry for oral or IV sedation

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Benzodiazepines Mechanism of Action Increase action of GABA Benzo’s bind to their own receptors that are part of the GABA network GABA + Benzo = ↑ Cl channel openings which also ↑ hyperpolarization of the nerve

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Benzodiazepines Adverse Reactions Wider margin safety than Barb’s (NBQ) Anterograde amnesia CNS depression (sedation is dose-related) Dental effects Xerostomia Swollen tongue Bitter or metallic taste Drug Interactions Metabolized by P-450 enzymes – many drug interactions Avoid alcohol & smoking (intensify effects & ↑ risk for toxicity) BOOK CORRECTION P.127 – SMOKING DOES NOT DIMINISH EFFECT BENZOS

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Benzodiazepines have which of the following modes of action? a.Reversal of schizophrenia b.Cause relaxation of the skeletal muscles c.Are analgesic in nature d.Are useful in treating attention deficit hyperactivity disorder

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ Benzodiazepines have which of the following modes of action? a.Reversal of schizophrenia b.Cause relaxation of the skeletal muscles c.Are analgesic in nature d.Are useful in treating attention deficit hyperactivity disorder

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ All of the following are benzodiazepines EXCEPT which one? a.Diazepam(Valium) b.Flurazapam(Dalmane) c.Fluoxetine(Prozac) d.Alprazolam(Xanax) e.Lorazepam(Ativan) f.Triazolam(Halcinon)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ All of the following are benzodiazepines EXCEPT which one? a.Diazepam(Valium) b.Flurazapam(Dalmane) c.Fluoxetine(Prozac) d.Alprazolam(Xanax) e.Lorazepam(Ativan) f.Triazolam(Halcinon) Remember: ~lam / ~pam

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Barbiturates

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Barbiturates Original sedative-hypnotic agent Benzo’s replaced barb’s for tx of anxiety & sleep disturbances Narrow TI More adverse effects – death with OD due to respiratory depression USES Hypnotic ( Causes hangover the next day unlike benzo’s) Anticonvulsant: Phenobarbital Pre-op for anxiety/sedation

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Barbiturates Mechanism of action: Same as benzo’s Respiratory depression greater Metabolism: very slow – prolong their actions P450 enzyme inducers like benzo (many drug interactions) Drugs very addicting Trying to quit “cold turkey” very dangerous (cardiac arrest)

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Barbiturates Barbiturates To Know Phenobarbital(Luminal) *Also used as anticonvulsant* Amobarbital(Amytal) Butabarbital(Butisol) Pentobarbital(Nembutal) Secobarbital(Seconal) All end in ~barbital Use this table instead of p.129, Table 11-2

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ The brief duration of general anesthetic action of an ultra-short- acting barbiturate is due to what factor? a.Rapid rate of metabolism in the liver b.Low lipid solubility, resulting in a minimal concentration in the brain c.High degree of binding to plasma proteins d.Rapid rate of redistribution from the brain to the peripheral tissues e.Slow rate of excretion by the kidneys

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. NBQ The brief duration of general anesthetic action of an ultra-short- acting barbiturate is due to what factor? a.Rapid rate of metabolism in the liver b.Low lipid solubility, resulting in a minimal concentration in the brain c.High degree of binding to plasma proteins d.Rapid rate of redistribution from the brain to the peripheral tissues e.Slow rate of excretion by the kidneys

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Other Sedative-Hypnotic Drugs

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Other Sedative-Hypnotic Drugs *All controlled substances* 1.chloral hydrate (Noctec) Prodrug Uses in dentistry: sedation for children, tastes bad Narrow TI 2.buspirone (BuSpar) Antianxiety 3.zolpidem(Ambien), eszopiclone(Lunesta), zaleplon(Sonata), Ramelteon(Rozerem) Insomnia, trouble falling asleep

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Centrally Acting Muscle Relaxants

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Muscle Relaxants Work directly on CNS to produce skeletal muscle relaxation Have no direct effect on striated muscle unlike benzo’s Uses TMD Muscle spasm Pharmacologic effects Some degree of sedative effect Xerostomia

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Centrally Acting Muscle Relaxants cyclobenzaprine (Flexeril) is the most popular Strongest muscle relaxant Sedation occurs 40% of patients

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. General Comments Special considerations Patients who use antianxiety agents should be driven to and from the dental appointment Drugs are not a substitute for patient management Drugs should not be substituted for patient psychological approach

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