CH9: Antianxiety agents

Learning objectives

⚫ Discuss the value of patient relaxation in dentistry.

⚫ Describe the mechanism of action, interactions, and dental relevance of the benzodiazepines and barbiturates.

⚫ Name and briefly describe the mechanism of action of the nonbenzodiazepine-nonbarbiturate sedative-hypnotics and the nonbenzodiazepine-nonbarbiturate receptor agonist.

⚫ Name a melatonin receptor agonist and summarize its actions.

⚫ Explain the workings of the centrally acting muscle relaxants and how they are used.

⚫ Name and briefly describe a few of the miscellaneous muscle relaxant agents

⚫ Discuss some general precautions about which the dental practitioner should be aware with the use of antianxiety agents.

General info

⚫ Individual responses to dental treatment vary!

⚫ Talk with the patient!

⚫ Do not assume patient is a “drug-seeker.”

⚫ Drug dose effects can also vary between patients!

Benzodiazepines

Alprazolam (Xanax)

Chlordiazepoxide (Librium)

Clonazepam (Klonopin)

Diazepam (Valium)

Lorazepam (Ativan)

Midazolam (Versed)

Temazepam (Restoril)

Triazolam (Halcion)

Benzodiazepines: Pharmacokinetics

⚫ ↑ lipid solubility = quicker onset of action

⚫ Cross the BBB, and placenta (Cat. D or X).

⚫ Metabolized in the liver

Benzodiazepines: Mechanism of action

⚫ GABA (γ-aminobutyric acid)- action enhanced

⚫ Benzodiazepine receptor agonists- ↓ anxiety

Benzodiazepines: pharmacologic effects

⚫ Behavioral- ↓ anxiety & panic; drowsiness

⚫ Antiseizure- diazepam; clonazepam

⚫ Muscle Relaxation

⚫ Large TI!!

Benzodiazepines: adverse reactions

CNS Depression- tolerance can occur

• Talkativeness, nightmares, hyperactivity-D/C drug

Anterograde Amnesia

Respiratory Effects

Cardiovascular Effects- ↓ HR and pulse rate

Visual Effects- contraindicated in narrow angle glaucoma

Dental Effects- xerostomia, increased salivation, swollen tongue, bitter/metallic taste

Thrombophlebitis- diazepam

GI- cramps/pain

Allergic reactions

Fetus malformations

Benzodiazepines: abuse and tolerance

Physical dependence and tolerance!!

Additive effects- other CNS depressants

Treatment of Overdose

⚫ Supportive therapy, emesis, activated charcoal and saline cathartic

⚫ Flumazenil (Romazicon)-antagonist (could precipitate withdrawal)

Benzodiazepines: drug interactions

⚫ CNS depressants, alcohol, CYP450, smoking, SSRIs

Benzodiazepines: medical uses

⚫ Anxiety

⚫ Insomnia (if a manifestation of anxiety)

⚫ Epilepsy

⚫ Alcoholism Treatment

⚫ Muscle Spasms

Benzodiazepines: dental procedures

⚫ Fast onset and short half-life preferred

⚫ Triazolam (fast onset, short half-life)

⚫ Diazepam (very fast onset, long half-life)

⚫ Alprazolam and lorazepam (intermediate onset, short half-life) *elderly

⚫ Midazolam (oral and IV)

Premedication- diazepam

Conscious Sedation- IV

Barbiturates

Thiopental sodium (Pentothal)

Pentobarbital (Nembutal),

Amobarbital (Amytal)

Phenobarbital (Luminal)

Barbiturates: Pharmacokinetics

⚫ Well absorbed orally and rectally; IV over IM

⚫ Redistribution from CNS to muscles to adipose tissue

⚫ Liver metabolism (short and intermediate)

⚫ Renal Excretion (long)

Higher rate of abuse

Barbiturates: mechanism of action

⚫ Enhance GABA-receptor binding

Barbiturates: pharmacologic effects

⚫ CNS Depression

⚫ Analgesia-via relaxation

⚫ Anticonvulsant

Barbiturates: adverse reactions

⚫ Sedative or hypnotic doses: exaggerated CNS; fetal harm

⚫ Anesthetic doses: lethal, depressed liver and kidney function

⚫ Acute Poisoning

Exaggeration of effects

Barbiturates: contraindications

porphria

Barbiturates: drug interactions

⚫ Stimulate liver microsomal enzymes (CYP450)

-potential for lots of drug interactions

(acetaminophen, warfarin, oral contraceptives)

Barbiturates: uses

⚫ Short acting- induction of general anesthesia

⚫ Long acting- epilepsy

Nonbenzodiazepine-nonbarbiturate sedative hyponotics

Buspirone (BuSpar)

⚫ Selective Anxiolytic

⚫ One week onset

⚫ First-pass metabolism

⚫ No tolerance or dependence

Nonbenzodiazepine Benzodiazepine Receptor Agonists

Activate receptor as if they were benzodiazepines

extra caution due to side effects

want patient to have someone to take them to appointment and home if taken before the day of the appointment

Zolpidem (Ambien, Ambien CR)

⚫ Short term management of insomnia

⚫ Fewer muscle relaxant and anticonvulsant effects

⚫ Side Effects- HA, drowsiness, dizziness, diarrhea; withdrawal; rebound insomnia; amnesia

Zaleplon (Sonata)

⚫ Lower risks of next day residuals.

⚫ Anterograde amnesia

Eszopiclone (Lunesta)

⚫ Newest agent; Longest half-life

Melatonin receptor agonist

Ramelteon (Rozerem)-acts on melatonin receptors

⚫ Insomnia

⚫ Melatonin type 1 and 2 receptors

⚫ Improved sleep latency, little effect on sleep maintenance

⚫ Adverse Effects: somnolence, dizziness, fatigue, HA, insomnia

⚫ Not a controlled substance

⚫ No tolerance, rebound insomnia, or withdrawal (yet)

Central acting muscle relaxants

carisoprodol (Soma),

orphenadrine (Norflex),

cyclobenzaprine (Flexeril)

Pharmacologic Effects

⚫ CNS Depression→ Sedative effects

⚫ Side Effects: GI, sedation, dizziness, allergic reactions, xerostomia

⚫ Flexeril-“strongest”, most sedating, most likely to cause xerostomia

⚫ Paraflex-discolored urine (purple-red)

Uses

⚫ Muscle spasms, temperomandibular disorder (TMD)

Miscellaneous agents (don’t worry :3)

Baclofen (Lioresal) Don’t worry

⚫ Spasticity from Multiple Sclerosis or spinal cord injuries or diseases

⚫Side Effects: drowsiness, weakness, HA, insomnia,

dry mouth, nausea

Tizanidine (Zanaflex) Don’t worry

⚫ Short acting muscle relaxant

⚫ Centrally acting α-adrenergic receptor agonist

⚫ Side Effects: sedation, drowsiness, hypotension, xerostomia

Dantrolene (Dantrium) Don’t worry

⚫ Treatment of spasticity from spinal cord injuries, cerebral palsy or multiple sclerosis

⚫ Side effects: drowsiness, photosensitivity

Precautions

⚫ Impaired elimination

⚫ CNS depressants-alcohol, OTC

⚫ Driving

⚫ Possibility of dependence

⚫ Suicide attempts

⚫ Pregnancy

⚫ Not analgesics

No alcohol, no driving