CNS Depressants Flashcards
(18 cards)
Prototype Drugs
Benzos: Diazepam (Valium) Triazolam (Halcion) Non-Benzos, Benzo Agonists (NBRAs): Zolpidem (Ambien) Eszopiclone (Lunesta) Alcohols: Ethanol (whiskey) Methanol (sterno) Other: Flumazenil (Romazicon), Disulfiram (Antabuse), Acamprosate (Campral), Baclofen, Naltrexone, Fomepizole (Antizol)
Dose related progression of drug effects
Sedation Disinhibition Ataxia Sleep Coma Death
Inverse Agonist
B-Carboline Carboxyethyl Ester
Binds to receptors to reduce GABA mediated Cl- conductance. Results in anxiety and muscle spasms and proconvulsant state
Short acting Benzos
Prototype: Triazolam - half life of 3 hrs
Metabolized to alpha-hydroxytriazolam (active metabolite) then Glucuronidation, then excreted in urine
Used to treat sleep disorders in the absence of anxiety; hangover free sleep.
Long acting Benzos
Prototype: Diazepam - half life of 30 hrs
Metabolized to Oxazepam (active metabolite) then Glucuronidation, then excreted in urine
Provides steady state drug concentration in CNS
Tolerance
Pharmacodynamic changes happen in the brain make drug less effective. Flumazenil can send chronic users into withdrawal.
NBRAs
Zolpidem (Ambien)
Eszopiclone (Lunesta)
Short acting hypnotics
Rapid absorption, no active metabolites
Binds to subtypes of benzo receptors and facilitate GABA mediated Cl- conductance. Can be reversed by Flumazenil
Zolpidem (Ambien)
Relatively selective for type 1 Benzo receptors
Half life of 2.6 hrs
No hangover
No noticeable effects on REM sleep
Eszopiclone (Lunesta)
Sedative hypnotic indicated for chronic treatment of insomnia
Rapid onset with half life of 6 hrs
Binds all 3 receptor types
No evidence of diminished efficacy over 6 month trial
Cross Tolerance
Observed between benzos and other sedative-hypnotic drugs
Ethanol mg%
80 mg% = legal driving limit
180-400 mg% = depression of cerebellum and loss of motor control
350-600 mg% = depression of midbrain function, spinal reflexes, depression of medullary respiratory control
Ethanol Mechanisms
Dissolves in lipid bilayer reduce viscosity and function
Increases GABA-mediated Cl- conductance through GABA-A receptors
Decreases glutamate-mediated cation conductance through subtype NMDA receptors
INcreases serotonin-mediated conductance through 5HT3 receptors on inhibitory interneurons
Ethanol Metabolism
NAD+ = dependent on alcohol dehydrogenase NADPH = dependent on microsomal ethanol oxidizing system
Both routes form acetaldehyde -> acetate
Effects of chronic ethanol ingestion
Peripheral neuropathy CNS deficits - dementia ventricular enlargement from more CSF (brain shrink) Decrease white matter Neuronal loss Shrinkage of neuronal nuclei
Ethanol Neurotoxicity - decrease of myelination
Wernicke-Korsakoff syndrome due to thiamine deficiency
Hepatic encephalopathy from fat deposits in liver
Teratogenicity
Fetal Alcohol Syndrome
Drug interactions of Ethanol
Potentiates CNS depressant and respiratory of other sedative-hypnotic drugs
May cause GI bleeding when combined with aspirin or other anticlotting drugs
Liver damage when combined with Acetaminophen
Reduction in activity of some antibiotics
Pharmacological treatment of alcoholism
Disulfiram (Antabuse) - inhibits aldehyde dehydrogenase - negative reinforcement
Naltrexone - decreases rewarding effects of alcohol
Acamprosate (Campral) - reduces glutamate neurotransmission and relapse in detoxified patients
Baclofen - GABA-B receptor agonist - decreases withdrawal symptoms
Methanol
Metabolized to formaldehyde by alcohol dehydrogenase which is metabolized to formic acid by aldehyde dehydrogenase (highly toxic)
Treat methanol poisoning with Ethanol or Fomepizole (inhibitor of alcohol dehydrogenase)
