• rapidly, completely absorbed
• distributes to all body tissues (crosses placenta)
• volume of distribution equivalent to total body water

• alcohol dehydrogenase met. low to moderate doses of ethanol
  • zero order kinetics (limited supply of coenzyme NAD)
  • met. lower in women
• microsomal ethanol oxidizing system kickes in above 0.1% blood ethanol (basis of breathalizer test)
  • partially responsible for development of metabolic tolerance
  • barbituates can increase MEOS by acting as inducers of P450

• drugs
  • oral hypoglycemics
  • metronidazole
  • some cephalosporins
• increases acetaldehyde, leading to sickness
  • nausea
  • vomitting
  • headache
  • hypotension

• inhibit metabolism with concurrently administered drug
• may lead to supra-additive CNS depression w/ drugs like:
  • tricyclic antidepressants
  • H1 antihistamines
  • narcotics
  • anticonvulsants (ex: benzodiazepines)

• induction of P450 enzymes, leading to increase in rate of metabolism of other drugs, so it reduces their effects
• drugs it effects:
  • acetamenophen will form more reactive intermediates which cause increase in risk of hepatotoxicity

1. ethanol can converted to acetaldehyde by:
   • use of alcohol DH (convert NAD to NADH)
   • use of microsomal ethanol oxidizing system

• general rule: always be thinking in g/100 mL
  • ex: 1% is equal to 1 g/100 mL
• 12 oz beer, 4 oz wine, 1.5 oz shot is equal to 15 g of ethanol
• Vd is 0.7 L/kg, so in 70 kg person its almost 50 L (0.7 x 70 = 49)
• 15g in 50 L
  • 0.3 g/L

• sedation
• subjective "high"
• slowing of reaction time

• excitement
• decreased inhibitions
• impaired motor function
• slurred speech
• ataxia

• disorientation
• confusion
• poor coordination

• stupor
• apathy
• vomiting
• incontinence

• abolished reflexes
• coma

• respiratory depression
• death

• enhance GABA_A actions
• inhibit Glu activation of NMDA receptor
  • indicated in cognitive function, learning, memory
• increase dopamine and opioids in synapse
• enhance serotonin in synapse (at 5-HT₃ R)
• enhance calcium activated, voltage gated potassium channels
  • causes hyperpolarization, leading to CNS depression

• metabolic tolerance (pharmacokinetic)- induction of metabolic enzyme expression
  • seen by microsomal ethanol oxidizing system
• functional tolerance (pharmacodynamic)- reduction of CNS sensitivity to ethanol due to adaptive changes in neurons
  • upregulation of NMDA receptors
  • upregulation of voltage gated calcium channels
  • down regulation of GABA_A receptors

• decreased gluconeogenesis and NAD depletion, leading to hypoglycemia
• fat accumulation in the liver, which eventually leads to hepatitis and cirrhosis

• inflammation
• bleeding
• scaring

All cause absorption defects

• altered steroid metabolism
• this leads to gynecomastia, testicular atrophy, salt retention

• HTN
• anemia
• ventricular hypertrophy
• myocardial infarction

• not a direct carcinogen
• it does increase the amount of acetaldehyde
• acetaldehyde can covalently modify DNA
• leads to increase in:
  • breast cancer
  • ovarian cancer
  • liver cancer
  • throat cancer
  • colon cancer

• peripheral neuropathy (most common neurological problem)
• Wernicke Korsakoff syndrome- associated with thamine deficiency (but rarely seen in absence of alcoholism)
  • ataxia
  • confusion
  • paralysis of extraocular muscles
  • can progress to coma and death
  • tx: IV thiamine

• mechanism- exact mechanism of teratogenic effects unknown
  • neurodegeneration
  • aberrant neuronal and glial migration in developing NS
• symptoms
  • mental retardation
  • growth deficiencies
  • microencephaly
  • underdevelopment of mid-face region

• cross toleratnt with other sedative hypnotic drugs
• physical dependence is marked by abstinence syndrome upon abrupt withdrawl

• maintain vital signs
• prevent aspiration of vomit
• IV dextrose
• thiamine to prevent Wernicke-Korsakoff syndrome

• symptoms
  • mild- anxiety, insomnia, tremors, nausea, vomiting, diarrhea, arrhythmias
  • severe- hallucinations, seizures
• tx
  • tapering doses of long acting benzodiazepine (ex: diazepine) for life threatening seizures
  • thiamine to prevent Wernicke-Korsakoff syndrome
  • clonidine and propanolol to reduce intensity of withdrawal

• indications- well motivated alcoholics under careful medical supervision
• mechanism of action
  • inhibits acetaldehyde DH
  • leads to accumulation of acetaldehyde, which will make the patient sick only if they consume ethanol
• side effects
  • nausea
  • vomitting
  • headache
  • hypotension
  • rare, and severe
    • marked respiratory depression
    • cardiovascular collapse
    • convulsion
    • unconsciousness

• naltrexone
• acamprosate
• SSRI's
• Topiramate

• mechanism of action- blocks effects of endogenous opioids in CNS, reducing rewarding effects of alcohol
  • shown by studies in primates reducing their alcohol preference
• route of administration- injection IM

• mechanism- exact unknown, but it is a antiepileptic medication
  • compensates for increased excitability in the braines of alcoholics during withdrawal
  • increases GABA_A activity while decreasing NMDA activity

• indication- epilepsy, migraines,reduce relapse to heavy drinking in recovering alcoholics
• mechanism
  • enhance GABA_A receptor activity
  • inhibit NMDA receptor activity

• health benefitsd only with moderate drinking, and greatest in older men (greater than 65)
• reduced risk of heart disease (increase HDL levels)
• lowers risk of DM in men and women
• usually with red wine (contains antioxidant resvertrol)

• VTA signals NA with dopamine (increase dopamine via ethanol)
• raphei nuclei releases serotonin to NA (increases serotonin via ethanol)

• metabolized by alcohol dehydrogenase to formaldehyde and formic acid
• metabolites lead to severe acidosis and retinal damage

• ethylene glycol metabolized via alcohol DH to oxalic acid
• oxalic acid causes acidosis and nephrotoxicity

Often associated with accidental ingestion in children

• IV ethanol or femepizol
  • they have a much higher affinity for alcohol dehydrogenase than methanol or ethylene glycol, so they wont be metabolized anymore
• dialysis