drugs for anxiety and panic disorders · drugs for anxiety and panic disorders robert l. balster,...
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DRUGS FOR ANXIETY AND PANIC DISORDERS
Robert L. Balster, Ph.D.Director, Institute for Drug and Alcohol Studies
Butler Professor of Pharmacology and ToxicologyVirginia Commonwealth University
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Anxiety/Panic Medications
1. Benzodiazepines2. Meprobamate (Miltown, Equanil)3.
Buspirone (BuSpar)
4.
Antihistamines5.
Beta Blockers
6.
Antidepressants and SSRIs
for panic
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Benzodiazepines Used for Anxiety/Panic Disorders
1. chlordiazepoxide (Librium)2. diazepam (Valium)3. oxazepam (Serax)4.
alprazolam (Xanax)
5.
chlorazepate
(Tranxene)6.
lorazepam (Ativan)
7.
prazepam (Centrax)
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Benzodiazepines Used as Sedative/Hypnotics
1.
flurazepam (Dalmane)2.
temazepam (Restoril)
3.
triazolam (Halcion)4.
estazolam (Prosom)
5.
quazepam (Doral)
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Benzodiazepines Specifically Indicated for Convulsive
Disorders
1.
clonazepam (Klonopin)
2.
clorazepate (Tranxene)
3.
diazepam (Valium, generic)
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Benzodiazepines Used as Anesthetics/Preanesthetics
1.
diazepam (Valium, generic)
2.
midazolam (Versed)
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Biodispositional Differences Between Benzodiazepines1.
Absorption
2.
Metabolism•
Oxidation
•
Conjugation 3. Active metabolite formation
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Biodispositional
Determinants of Drug Effects
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Drug Accumulation
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N
N
Cl
OCH3
DIAZEPAM
N
N
Cl
OCH3
OH
TEMAZEPAM
N
N
Cl
O
DESMETHYLDIAZEPAM
N
N
Cl
O
OH
OXAZEPAM
OXAZEPAM GLUCURONIDE
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Benzodiazepine metabolism
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Diazepam Conversion to Desmethyldiazepam
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Diazepam and Desmethyldiazepam
accumulation
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Half-lives of Benzodiazepines
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Diazepam half-life and Age
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Benzodiazepine Duration of Action Summary
Short Intermediate Long
oxazepam alprazolam chlordiazepoxide
triazolam temazepam diazepam
midazolam clonazepam
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CNS Depressant Dose Effect Curves
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Mechanism of Action of Benzodiazepines
1.
Bind to selective receptors
2.
Enhance inhibitory neurotransmission
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GABA Channel
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GABA Channel Subunit Anatomy
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GABA Benzodiazepine Receptor Complex
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Role of Alpha Subunits
•
Alpha subunit critical for actions of benzodiiazepines
•
Alpha2
and/or alpha3
containing receptors are targets for antianxiety
effects of
benzodiazepines•
Alpha1
containing receptors involved in sleep
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Zolpidem (Ambien and Ambien CR), Zaleplon (Sonata) and
Eszopiclone (Lunesta)•
Not benzodiazepine structures (“Z-drugs”)
• Have GABA-agonist effects by acting at benzodiazepine receptor
• Selectivity for BZ1 (Ω1
) subtype (containing α1
subunits)•
Used for sleep disorders
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Benzodiazepines Differ in Agonist Efficacy
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Benzodiazepine Antagonists
•
flumazenil (Mazicon)
•
reverse acute effects of benzodiazepines, either when taken alone or with other depressants
•
precipitate withdrawal
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Clinical Uses of Benzodiazepines
1.
Anxiety and Panic Disorders2.
Sleep Disorders
3.
Convulsive Disorders4.
Muscle Relaxation
5.
Anesthesia6.
Alcohol and Barbiturate Withdrawal
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Side Effects of Benzodiazepines
1. CNS Depression
--
sedation--
motor incoordination
2.
Paradoxical Excitement3.
Confusion and Amnesia
4.
Drug Interactions
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Benzodiazepine Drug Interactions
1.
Alcohol2.
Sedatives and Anticonvulsants
3.
Antihistamines4. Opioid Analgesics5. Antidepressants6. Metabolic Interactions
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Side Effects of Benzodiazepines
5. Abuse and Misuse
6. Physical Dependence
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Signs and Symptoms of Benzodiazepine Withdrawal
1.
Anxiety2.
Insomnia
3.
Tremors and Hyperreflexia4.
Nausea and Vomiting
5.
Delirium6.
Convulsions
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graph
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Pharmacology of Buspirone (BuSpar and generic)
1.
No CNS depressant effects
2.
Probably acts on serotonergic systems
3.
No abuse liability
4.
Poor transition from benzodiazepines to buspirone
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Pharmacology of Hydroxyzine (Vistaril, Atarax, generic)
1.
Antihistamine
(H1 Blocker)
2.
Psychosomatic allergies, etc.3.
Side effects
•
CNS depression•
anticholinergic
•
drug interactions
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Pharmacology of Propranolol
1.
Beta-adrenergic blocker
2.
Blocks sympathetic nervous system signs of fear and anxiety
3.
Used for situation-specific anxiety and acute panic symptoms