Drug of abuse

Mechanism: binds GABA-Ar complex (like benzo and barbs), increases Cl- influx and augment GABA transmission; also inhibits glutamate on NMDAr;  Long term chronic use down regulates GABA receptors and up regulates NMDA receptors (tolerance)

Pharmacokinetics: alcohol dehydrgenase metabolizes alcohol in GI tract; crosses BBB easily

Effects: CNS low = disinhibition, decreased anxiety, mild euphoria, sedation; CNS higher = impaired funtion and judgement, slurred speach, ataxia

Metabolism: EtOH -> ADH -> acetaldehyde -> aldehyde dehydrogenase -> acetate; At low concentrations = zero order kinetics (independent of concentration), at higher concentrations = 1st order kinetics; 

Acetaminophen tox: since EtOH induces CYP2E1 it will metabolize acetaminophen to it's toxic metabolite faster, effects peak during hangover (worst time, most likely time)

Phenytoin for DT

Mechanism: inhibits aldehyde dehydrogenase, making pt sick when they drink from acetaldehyde buildup, could be dangerous

Long duration, don't drink for 3-4 days following administration

Dangerous and not recommended

Other Drugs: Diazepam (Valium^®) 

Chlordiazepoxide (Librium^®); long acting benzo's that taper withdrawal

Oxazepam(Serax) is used if there is liver damage

Use: Blocks the ability of EtOH to stimulate the reward pathway

Side effects: nausea, LIVER DAMAGE (large doses) so contraindicated

Mechanism: Opioid receptor antagonist, since EtOH stimulates release of B-endorphins that act on opioid receptors; will also block other opiods too

Other Drugs: Nalmefene (ReVex^®)- longer duration, less likely to cause liver damage

Mechanism: Structural analogue of GABA

Use: Restore normal NMDA and GABA balance -> GABA and glutamate transmission

Tx of alcoholism: increases abstinence, no liver toxicity; restoration of balance decreases the anxiety, hyper excitability and sleeplessness that occur from the imbalance

Alcohol dehydrogenase inhibitor

Uses: Ethylene glycol (antifreeze) and methanol poinsoning

Administration of fomepizole or ethanol are given in both cases