1) Describe the interaction between benzodiazepines and GABA at the GABAA receptor.
2) Apply this to the overdose potential of benzodiazepines.
1) acts at a site on GABA-A receptors that is separate from the GABA site itself.
•From this site the action of GABA in opening chlorine ion channels is increased, but no effect without GABA.
2) Benzos have a very low overdose potential
What are the primary indications for
1) Alprazolam: panic disorder, anxiety disorders and PMS
2) Lorazepam: generalized anxiety disorder; also being used for alcohol withdrawal instead of chlordiazepoxide
3) Meprobamate: short-term anxiety and sedative-hypnotic
What is the procedure for weaning a patient off of a Benzodiazepine?
•Taper 25% per week to 50% of dose, then 1/8th dose every 4-7 days.
What is a special population to be careful of when prescribing meprobamate and why?
•Pregnancy Category D.
Associated with congenital malformations.
Differentiate the site of action for azapirones versus BZs.
-These do not act at GABA receptors.
-These act on 5HT1A receptors, perhaps to inhibit 5HT release.
What is one advantage of buspirone over BZs?
Less motoric disruption.
Differentiate the site of Z-hypnotic versus BZ action.
Zolpidem (Ambien) and Zaleplon (Sonata)
Acts at GABA-A type 1 only
What is the general nature of toxicities to benzodiazepines?
•Most are due to sedative actions
•Some teratogenicity in first trimester
•Additive effects with alcohol are particularly important
•Other Adverse effects
-Cognitive impairment- Sedation and Memory
-Potentiation of CNS depressants
-Abuse and dependence
-Possible teratogen in first trimester
-Low suicide potential
What is a special population to be careful of when prescribing benzodiazepines and why?
•Women of child-bearing age
•Pregnancy: teratogenicity in first trimester
What is the main problem with use of benzodiazepines for extended periods?
What has been demonstrated to happen with the discontinuance of alprazolam in various studies?
•Seizures, delirium, and withdrawal symptoms
-a relapse of the condition, including a rebound in panic attacks and anxiety, and/or the development of withdrawal frequently occurs.
Explain the dichotomy of risk and benefit to using 4 mg daily of alprazolam to treat panic disorder.
•Effective treatment of panic disorder with alprazolam often has required dosages exceeding 4 mg daily
•risk and severity of dependence is increased in patients receiving such dosages for prolonged periods
What is the demonstrated efficacy of chlordiazepoxide for long-term use (i.e., for longer than 4 months)?
efficacy of chlordiazepoxide for long-term use (i.e., for longer than 4 months) has not been established, and the need for continued therapy with the drug should be periodically reassessed
1) What is the primary indication for midazolam?
2) What are its two routes of administration?
1) preoperative sedation, anxiolysis, and anterograde amnesia
2) IM or IV
What are the advantages and disadvantages in the use of buspirone (BuSpar) for persistent anxiety?
•The advantages of buspirone (BuSpar)
-Effective relief of persistent anxiety within 2 to 4 weeks
-No potential for abuse, dependence or withdrawal syndrome
-Patients maintain cognitive skills (e.g. memory function) and psychomotor skills (e.g. ability to drive a car)
-Can be used with alcohol and other CNS agents
-Anxioselective in the serotonin synapse; modulates serotonin at specific receptors (5HT1A)
•The disadvantages of buspirone
-May be less effective in recent benzodiazepine users
-Gradual onset of action: 2 to 4 weeks for effect
-Not effective in panic disorder
What is the indication for which the efficacy of buspirone has been established principally in outpatient settings?
Generalized Anxiety Disorder in which anxiety was present for periods of 1 month up to 1 year (average symptom duration: 6 months) of continual duration
What are the most frequent adverse effects of zolpidem tartrate in trials involving regular versus extended release formulations?
•Regular- most frequently involves nervous system and GI tract
Drowsiness, dizziness, and diarrhea
In prolonged period- dizziness and drugged feelings
•Extended release- tend to be dose related particularly for nervous system (most common) and GI effects
Headache, somnolence and dizziness
What are three complex sleep-related behaviors associated with use of zaleplon?
•Sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event)
•Making phone calls while asleep
•Preparing and eating food while asleep