Anxiolytic Agents (aka Sedative - Hypnotic Agents)2 Flashcards
Barbiturates: Increase in dose above that needed for hypnosis-sleep leads to state of general anesthesia - can progress to ___________, ultimately resulting in coma and death
depression of respiratory and vasomotor centers
Benzodiazepines: Non-linear and less steep dose-response relationship indicates that much greater dosage increments are required to achieve CNS depression more profound than hypnosis-sleep - consistent with their ___________________
greater margin of safety
The great majority of sedative-hypnotic drugs act to facilitate the action of GABA (γ-aminobutyric acid) at the ______________
GABAA receptor-chloride channel complex
Both benzodiazepines and barbiturates (each at a separate binding site) indirectly increase the GABA-ergic effect to diminish
neuronal excitability further.
Benzodiazepines intensify the effect of GABA, while ____________ the effect of GABA (both actions requiring presence of GABA for this effect). At high concentrations, barbiturates interact directly with the GABA receptor (presence of GABA is not required for effect).
barbiturates prolong
Barbiturate action is ___________________(glutamate). With barbiturates, greater CNS depression and full surgical anesthesia can be obtained, thus they have a lower safety margin.
less selective and also depresses excitatory neurotransmitters
_____________ - eszopiclone - zaleplon are non-benzodiazepines that interact with the benzodiazepine binding site as agonists. Commonly referred to as “Z”-drugs.
Zolpidem
__________________ an antagonist at the benzodiazepine binding site, reverses the CNS effects of benzodiazepines
Flumazenil
Benzo best in liver
L and O
• Benzodiazepines in clinical use today bind to GABA-chloride channels with both α1 and α2/α5 subunits and result in both ____________
sleep and anxiolysis
Anxiolysis
(Sedation). Described as a decrease in responsiveness to a given level of stimulation, with relief of anxiety, occurring at the lowest effective doses of these agents
Anxiolysis is usually accompanied by some impairment of psychomotor function. Behavioral disinhibition may also occur
Non-sedative anxiolytics exist (buspirone and propranolol), but most benzodiazepine antianxiety agents in use today also produce sedation
Anticonvulsant Effects
Higher doses of most barbiturates and some benzodiazepines inhibit formation and spread of seizure activity in cortical neurons. Some do so at doses that do not cause severe sedation or effects on mental or motor activity (phenobarbital, clonazepam). Diazepam (or lorazepam) is drug of choice for status epilepticus. [Discussed further in separate lecture on AEDs]
Muscle Relaxation.
Action to inhibit spinal cord polysynaptic reflexes may aid in muscle spasms. Effect requires high doses, thus usually accompanied by significant CNS depression.
Hypnosis
All of the benzodiazepine agents will induce sleep at high enough doses
Anesthesia
Short-acting barbiturates (thiopental) used to induce-maintain surgical anesthesia. Benzodiazepines are NOT capable of inducing or maintaining anesthesia but are used as adjuncts for their anxiolytic and amnesia-producing properties).