Alcohol: use & abuse Flashcards
What can be given for acute methanol or ethylene glycol intox?
ethanol and fomepizole
What drugs are given for EtOH dependence?
Disulfiram
Naltrexone
Acamprosate
What to give to a pt in EtOH withdrawal?
thiamine and BNZs
how is EtOH metabolized?
- ethanol to acetaldehyde via alcohol dehydrogenase
* inhibited by fomepizole - Acetaldehyde to Acetate via Aldehyde DH
* inhibited by disulfiram
why is disulfiram used?
to encourage abstinence from alcohol by preventing the metabolism of acetaldehyde – accumulation of this leads to feeling of nausea and flushing rxn
Asian flush why?
polymorphisms in aldehyde DH
What is a problem w/ disulfiram in some alcoholics?
- find acetaldehyde pleasure due to VTA which promotes DA relases.
- acetaldehyde condenses w/ DA to produce salsolinol
- still unpleasant in periphery
- Asians w/ polymorphism experience more positive feelings after alcohol. Allele is associated w/ lower prevalence of abuse and alcoholism
What effects does alcohol have on other drugs
- inducer of CYP2E1
- this increases acetaminophen conversion to highly reactive NAPQI (highly toxic)
- give N-acetylcysteine to provide fresh conjugate substrate for reactive intermediate to be safely detoxified
What happens w/ the following BAL levels?
0
400
< 50 : limited muscular coordination
50-100: pronounced incoordination
100-150: mood and personality changes, intoxication over the legal limit in most states
150-400: N/V, marked ataxis, amnesia, dysarthria
>400: coma, respiratory insufficiency and death
impact of EtOH on key neurochemical systems
- GABA release, increase receptor density
- inhibits NMDA, w/ chronic use up-regulation
- increase DA and effects on ventral tegmentum/nucleus accumbens
- increase ACTH
- release of Beta endorphins, activation of mu receptors
- in crease 5HT
- increased CB1 activity (cannabinoid)
what effects does EtOH have on other systems besides the CNS
- CV depressant
- relaxes vascular SM: vasodilation, hypothermia, increased gastric bloodflow
- relaxes uterine SM
factors affecting blood alcohol level
- Vd: more weight = larger Vd = lower BAL
- BMI: more body fat = smaller Vd = higher BAL
- Female gender: higher BAL
- Metabolism: 0 order, 1 drink per hour
- Adaptation: behavioral and neural adaptation, enzyme induction
Chronic effects of EtOH
- Liver: decreased gluconeogenesis –> hypoglycemia, fatty liver –> hepatitis, cirrhosis, liver failure
- GI: bleeding, scarring –> absorptive and nutritional deficiency
- CNS - peripheral neuropathy, Wernicket Korsakoff syndrome (ataxia, confusion, ocular muscle paralysis)
- endocrine - gynecomastia, testicular atrophy
- CV - HTN, anemia, dilated cardiomyopathy, arrhythmias w/ binge, modest consumption increases HDL and may protect against CHD
- Neoplasia- GI cancer
- Immune system - pancreatitis, infectious pneumonia
What is thiamine deficiency crucial
- can’t make and replenish critical amino acids and proteins
Fetal alcohol syndrome
- crosses placenta easily and fetal blood reflect maternal levels.
- intrauterine growth retardation
- microcephaly
- poor coordination
- midfacial underdevelopment
- minor joint anomalies
- congential heart defects and subtle neurologic deficits
typical treatment of alcoholics in ED
- ABCs
- dextrose: compensate for hypoglycemia
- thiamine - protect against wernicke-korsakoff syndrome
- correct electrolyte issues
EtOH withdrawal symptosm
insomnia, tremor, anxiety, rarely seizures
- N/V, diarrhea, arrhythmias
treatment of EtOH withdrawal
BNZ sedative: diazepam but when concerned for hepatic impairment think lorazepam
Thiamine
Correct electrolytes
Drug interactions of Alcohol
- increased tertogenicity and increased absorption
- additive CNS depressive actions w/ drugs
- increased toxicity of acetaminophen
- increased risk of bleeding w/ NSAIDS and anticoagulants
- increase risk of hypglycemia in diabetics on meidcations
what other drugs have disulfiram like effects
- sulfonylureas, cefotetan, keotconazole, procarbazine
MOA of acamprosate
weak NMDA blocker
- activation of GABA receptor
- may decreased mild protracted abstinence syndromes w/ decreased feeling of need for EtOH
why is naltrexone used
- decreased drinking through decrease feelings of reward w/ alcohol and/or decrease cravings
Where do naltrexone, acamprosate work in the corticomesolimbia dopaminergic pathway
- naltrexone at VTA
- Acamproate - glutamate at VTA and NA, GABA at VTA
toxicity of Ethylene glycol and methanol
- both use EtOH DH to form toxic metabolites
- ethylene glycol –> oxalic acid leading to acidosis, nephrotoxicity
- metanol –> formaldehyde and formic acid –> severe acidosis, retinal damage
- treat w/ fomepizole or ethanol for a competitive inhibitor (give enough to maintain BAL of at least 100 to ensure E saturation)
