Anxiolytic agents - French Flashcards
- Describe the general mechanism of action of the sedative-hypnotic agents.
- Discuss the relation between drug effects on GABA vs glutamate function as it relates to clinical uses and safety margins of barbiturates vs benzodiazepines.
- Relate differences in the pharmacokinetic disposition of benzodiazepines to their clinical uses.
- Describe the side effect profile of the benzodiazepines as it relates to their limited utility in treatment of anxiety.
- Describe the unique pharmacodynamic profile of buspirone and its role in the treatment of anxiety.
- List additional clinical indications for benzodiazepines.
Benzodiazepines: Diazepam - Alprazolam - Lorazepam - Oxazepam - Flumazenil - Midazolam
Barbiturates: Pentobarbital - Phenobarbital
x
Sedative-Hypnotic Drugs are a chemically heterogeneous class of drugs characterized by graded dose-dependent depressant effects on the CNS. Distinguished from other drugs that also cause CNS depression by their mechanism. They _____ GABA neuronal inhibition and/or ____ glutamate neuronal excitation
augment GABA inhibition
inhibit Glutamate excitation
How does GABA decrease neuronal excitability?
GABA binding to its receptor opens an ion channel to increase Cl- conductance. This results in membrane hyperpolarization that diminishes neuronal excitability and neurotransmission.
Can full surgical anesthesia be obtained with benzodiazepines?
No.
[Benzodiazepines do not affect excitatory neurotransmitters as do other CNS depressants such as barbiturates and general anesthetics and thus are incapable of inducing and maintaining surgical anesthesia.]
What drug is the antidote to benzodiazepines?
Flumazenil, an ANTAgonist at the benzodiazepine binding site, reverses the CNS effects of benzodiazepines.
What are the “Z-drugs”? What differentiates them from benzos?
[Not an LO, but mentioned 2x in the handout]
“Z-drugs” (zolpidem, zaleplon, eszopiclone)
–>Not benzodiazepines structurally and bind only to GABA-chloride channels with α1 subunits resulting in SLEEP WITHOUT ANXIOLYSIS (reduced potential for dependence)
Low doses of benzos/barbituates will produce anxiolysis. Define the term, and state two side effects that often accompany these agents.
“a decrease in responsiveness to a given level of stimulation, with relief of anxiety.”
Impairment of motor function, sedation
At higher doses than required for anxiolysis, what can barbituates and benzodiazepines be used for?
Anticonvulsant effects.
Muscle relaxation.
Hypnosis (sleep).
____ is the drug of choice for status epilepticus.
Diazepam (or lorazepam)
What is the role of barbituates and benzodiazepines in surgery/anesthesia?
Barbiturates (thiopental): produces complete sedation at high doses
Benzodiazepines: Adjunct agent that produces anterograde amnesia, reduces anxiety
Does tolerance develop to the anxiolytic agents?
Yes. The anxiolytic effect tends to remain, the sedative and anticonvulsant effects less so.
Which benzodiazepines are well-absorbed orally?
Diazepam, alprazolam
[and triazolam ]
_____ has consistent and reliable intramuscular absorption
Lorazepam
How are benzodiazepines eliminated?
Phase I: CYP450 metabolism
Phase II: glucuronidation
–> elimination in the urine
These benzodiazepines are good choices for use in the elderly with impaired phase I metabolic pathways and in patients with hepatic dysfunction.
Why?
Lorazepam and oxazepam (and temazepam)
–> metabolized directly to the inactive glucuronides (NO P450 step) and as a result have shorter half-lives and fewer problems with cumulative and residual effects
