Alcohol: use & abuse Flashcards
(24 cards)
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)
