Pharmacology - Test 2 - CNS Depressants Flashcards Preview

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Flashcards in Pharmacology - Test 2 - CNS Depressants Deck (22):

Dose-related progression of effects

Sedation (anti-anxiety effects)
Behavioral disinhibition
Ataxia / nystagmus
Sleep (hypnosis)
Coma, respiratory depression,
cardiovascular depression


prototype drug classes

benzos, non-benzo benzo agonists (NBRAs)


benzodiazapene mechanism

enhance GABA-mediated Cl- conductance and neuronal inhibition


chronic use can lead to

tolerance and dependence. abrupt wthdrawal can lead to severe symptoms


benzos and sleep stages

decrease the latency to onset of sleep
decrease number of awakenings
increase total sleep time
decrease stage o (wakefulness)
increase time in stage 2 (major fraction of non-REM sleep)
decrease slow wave sleep (stages 3 & 4)
time in REM sleep is shortened, but this is compensated by an increase in the number of REM cycles, mostly late in sleep time



Ambien and Lunesta


NBRA mechanism

bind to subtypes of benzodiazepine receptor and facilitate GABA-mediated Cl- conductance and neuronal inhibition. The effects of zolpidem(ambien) and eszopiclone (lunesta) are antagonized by flumazenil.


Zolipidem (Ambien)

selective for the type 1 benzodiazepine receptor. It is rapidly absorbed and eliminated with a half-life of ~2.6 h. Useful for the acute treatment of sleep disorders


Eszopiclone (Lunesta)

first sedative-hypnotic indicated for chronic treatment of insomnia. It also has a rapid onset of action, but a longer half-life (~6h) than zolpidem. Appears to bind to all three benzodiazepine receptor types;


THerapeutic uses of benzos and NBRAs

anxiety, panic attacks, and post-traumtic stress disorder, muscle spasms, spasticity associated with cerebral palsy, and other spastic disorders, convulsive disorders (status epilepticus), sleep disorders, sedative-hypnotic withdrawal symptoms, pre- and co-anesthesia, relaxation for endoscopic procedures



treatment of benzo/NBRA overdose


Benzo/NBRA drug interactions

potentiate CNS depression of other sedative-hypnotics



dose-related progression of CNS depression. most sensitive CNS structures are the polysynaptic reticular activating system and the cerebral cortex


ethanol mechanism

ethanol dissolves in the lipid bilayer of plasma membranes, reducing membrane viscosity and disrupting protein function
·  increases GABA-mediated Cl- conductance through the GABA-A receptor
·  decreases glutamate-mediated cation conductance through subtypes of NMDA receptors
increases serotonin-mediated cation conductance through 5HT3 receptors located on inhibitory interneurons


ethanol pharmacokinetics

rapid absorption from small intestines, stomach, and colon; maximal concentration in blood is 30-90 min.
elimination : 90-98% is oxidized
follows zero order kinetics (7-10 g /h; takes ~ 5 h to metabolize 4 oz of Jack Daniels)
oxidized by two enzyme systems:NAD+ and NADPH


chronic alcohol use

peripheral neuropathy
CNS deficits - dementia
-ventricular enlargement due to brain shrinkage and increased CSF volume
-decreased white matter
-neuronal loss cortex, hypothalamus and cerebellum
-shrinkage of neuronal nuclei
Ethanol neurotoxicity
Wernicke-Korsakoff syndrome due to thiamine deficiency
Hepatic encephalopathy


thiamine deficiency secondary to chronic ethanol use

-inadequate nutritional intake
-decreased uptake of thiamine from the gastrointestinal tract
-impaired thiamine utilization


Pharmacological treatment of alcoholism

disulfiram (Antabuse) – inhibitor of aldehyde dehydrogenase
naltrexone – decreases the rewarding effects of alcohol
acamprosate (Campral) – reduces glutamate neurotransmission – reduces relapse in de- toxified patients
baclofen – GABA-B receptor agonist- decreases alcohol withdrawal symptoms and promotes abstinence; reduces alcohol-related anxiety and craving.

All should be used in combination with cognitive/behavioral therapy



used as a substitute for ethanol or accidental poisoning
·       treat with fomepizole (Antizol; inhibitor of alcohol dehydrogenase)

correct the metabolic acidosis


methanol metabolism

methanol is metabolized to formaldehyde by alcohol dehydrogenase; formaldehyde is metabolized to formic acid by aldehyde dehydrogenase


formaldehyde and formic acid

highly toxic: metabolic acidosis, blindness, seizures, coma, death


tx for methanol poisoning

ethanol or fomepizole. correct the metabolic acidosis