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

DH206 PharmacologyChapter 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


Definitions


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


Mechanism of ActionADME


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!”



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


Benzodiazepine’s


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


Benzodiazepines

Uses of Benzo’sAnxiolytic (relief of anxiety)Sedative Hypnotic (induce sleep)Muscle relaxantAnticonvulsant – CH16Alcohol withdrawalConscious sedation in dentistry or pre-op anti-anxiety agent (Remember from CH10)

ALL NBQ INFO!


BenzodiazepinesUSE THIS TABLE FOR DRUGS TO KNOW, NOT TABLE 11-1, P.125Benzodiazepines UsesAlprazolam(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 sedationVery long half-life

Midazolam(Versed) Used in dentistry for oral or IV sedation


BenzodiazepinesMechanism 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


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


NBQBenzodiazepines have which of the following modes of action?

a. Reversal of schizophreniab. Cause relaxation of the skeletal musclesc. Are analgesic in natured. Are useful in treating attention deficit hyperactivity disorder


NBQBenzodiazepines have which of the following modes of action?

a. Reversal of schizophreniab. Cause relaxation of the skeletal musclesc. Are analgesic in natured. Are useful in treating attention deficit hyperactivity disorder


NBQAll 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)


NBQAll 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


Barbiturates


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

USESHypnotic ( Causes hangover the next day unlike benzo’s)

Anticonvulsant: PhenobarbitalPre-op for anxiety/sedation


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)


Barbiturates

Barbiturates To KnowPhenobarbital(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


NBQThe brief duration of general anesthetic action of an ultra-short-acting barbiturate is due to what factor?

a. Rapid rate of metabolism in the liverb. Low lipid solubility, resulting in a minimal concentration in the brainc. High degree of binding to plasma proteinsd. Rapid rate of redistribution from the brain to the peripheral tissuese. Slow rate of excretion by the kidneys


NBQThe brief duration of general anesthetic action of an ultra-short-acting barbiturate is due to what factor?

a. Rapid rate of metabolism in the liverb. Low lipid solubility, resulting in a minimal concentration in the brainc. High degree of binding to plasma proteinsd. Rapid rate of redistribution from the brain to the peripheral tissuese. Slow rate of excretion by the kidneys


Other Sedative-Hypnotic Drugs


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


Centrally Acting Muscle Relaxants


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


Centrally Acting Muscle Relaxants

• cyclobenzaprine (Flexeril) is the most popular • Strongest muscle relaxant• Sedation occurs 40% of patients


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


Documents

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