Anxiolytic Agents (aka Sedative - Hypnotic Agents)2 Flashcards Preview

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Flashcards in Anxiolytic Agents (aka Sedative - Hypnotic Agents)2 Deck (20):

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.



__________________ an antagonist at the benzodiazepine binding site, reverses the CNS effects of benzodiazepines



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



(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.



All of the benzodiazepine agents will induce sleep at high enough doses



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).



. A common feature when agents are used continuously in high doses. May require increase in dose to maintain effect. Metabolic and pharmacodynamic components of tolerance are seen. Occurs rapidly to sedative and anticonvulsant effects, less so to anxiolytic action.


All benzodiazepines have similar pharmacodynamic actions so differences in their pharmacokinetic properties are

important factors in determining their clinical usage.


• Oral

All benzodiazepines have similar pharmacodynamic actions

Rapidity of oral absorption is factor in determining utility in prn usage (situational anxiety, difficulty in falling asleep)
Diazepam, alprazolam, and triazolam have rapid oral absorption
Oxazepam and temazepam have slow oral absorption.


All benzodiazepines have similar pharmacodynamic actions

• Intramuscular

This route is used when a faster onset is desired or oral access is compromised
Lorazepam has consistent and reliable intramuscular absorption
Diazepam and chlordiazepoxide have poor IM bioavailability - poor water solubility in ECF


Barbiturates are classic inducers of _____________ and represent a major source of clinically significant drug interactions that has contributed to their declining use

CYP450 enzymes