Pharmacology - Test 2 - CNS Depressants

Question 1

Dose-related progression of effects

Answer 1

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

Question 2

prototype drug classes

Answer 2

benzos, non-benzo benzo agonists (NBRAs)

Question 3

benzodiazapene mechanism

Answer 3

enhance GABA-mediated Cl- conductance and neuronal inhibition

Question 4

chronic use can lead to

Answer 4

tolerance and dependence. abrupt wthdrawal can lead to severe symptoms

Question 5

benzos and sleep stages

Answer 5

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

Question 6

NBRAs

Answer 6

Ambien and Lunesta

Question 7

NBRA mechanism

Answer 7

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.

Question 8

Zolipidem (Ambien)

Answer 8

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

Question 9

Eszopiclone (Lunesta)

Answer 9

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;

Question 10

THerapeutic uses of benzos and NBRAs

Answer 10

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

Question 11

Flumazenil

Answer 11

treatment of benzo/NBRA overdose

Question 12

Benzo/NBRA drug interactions

Answer 12

potentiate CNS depression of other sedative-hypnotics

Question 13

ethanol

Answer 13

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

Question 14

ethanol mechanism

Answer 14

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

Question 15

ethanol pharmacokinetics

Answer 15

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

Question 16

chronic alcohol use

Answer 16

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

Question 17

thiamine deficiency secondary to chronic ethanol use

Answer 17

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

Question 18

Pharmacological treatment of alcoholism

Answer 18

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

Question 19

methanol

Answer 19

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

   correct the metabolic acidosis

Question 20

methanol metabolism

Answer 20

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

Question 21

formaldehyde and formic acid

Answer 21

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

Question 22

tx for methanol poisoning

Answer 22

ethanol or fomepizole. correct the metabolic acidosis