M5 L1: ethanol (alcohol) Flashcards
what is alcohol
- widely consumed and socially accepted
- most commonly abused drug in the world
what is the chemical structure of alcohol
OH- (functional group) and C atom (saturated)
valence of 4
make sure to look at chemical structures of methanol, ethanol, propan-2-ol, ethan-1,2-diol on the slideshow
chemical structure of ethanol (rubbing alcohol)
C2H5OH
used as disinfectant
what is ethylene glycol chem structure
C2H4(OH)2
what is ethanol
- small molecule
- produced by sugar fermentation
- water soluble
- organic solvent
- volatile and flammable
(can pass blood-brain barrier which is why it has CNS symptoms)
what is ethanol
used as: recreational drug, antiseptic/disinfectant, chemical solvent, fuel
how is ethanol absorbed
rapidly through the GIT(stomach)
what is peak blood level for ethanol
within 30 minutes (F>M)
what is the distribution of ethanol
rapid - increased Volume distribution close to total body water
how is ethanol metabolized
liver (90%) - oxidation - 2 pathways…
1st step stim or catalyzed by alcohol dehydrogenase (MEOS)
2nd step by aldehyde dehydrogenase
can ethanol cross membranes
yes!
ex: BBB and placenta
how is ethanol excreted
- kidney thru urine
- lungs thru breath (DUI)
what can fomepizole inhibit
alcohol dehydrogenase
what can disulfiram inhibit
alc dehydrogenase
(disulfiram works to treat alc use disorder [results in unpleasent sypt to deter person from drinking], fomeprizole does ethylene glycol treatment and methanol poisoning)
what is MEOS
microsomal ethanol-oxidizing system
what is fomepizole
treatment of methanol or ethylene glycol poisoning
what is disulfiram
treatment of alcohol dependence
what is the rate of metabolism for ethanol
zero order kinetics (= independent of time and concentration)
depends on enzymes
what are the 2 pathways for metabolism that ethanol uses
- alcohol dehydrogenase (primary pathway) …
- MEOS (chronic alcoholism) … Acetaldehyde -> Acetate -> CO2 or acetyl CoA
what does acetaldehyde accumulation cause
facial flushing, nausea, vomiting, dizziness, headache
how does alcohol do what it does to the CNS
- affects several neurotransmitter systems involved in the brain’s reward pathways mainly GABA and glutamate
- increased GABA-mediated inhibition thru GABAa receptor
- decreased glutamate-mediated excitation thru NMDA receptor
GABA has a sedative effect, glutamate has an excitatory effect
what does ethanol do to dopamine, opioid, and cannabinoid pathways
increase/stim
increase in dopamine - makes you feel good/high/satisfied this can lead to addiction
stim of opioid channel - eases pain, makes you feel relieved
what is the mech of action for a high dose of ethanol
Na channel blockade, electrical stabilization and decreased conduction of nerve action potential (direct effect)
overall inhibiting depolarization
what are the effects of alcohol on the body? (ethanol pharmacodynamics)
- CNS depression
slower reaction times, sedation, impaired motor function, slurred speech, emesis, coma, respiratory death
effect of alcohol on the heart (pharmacodynamics)
- decreased myocardial contractility
- high dose: dysrhythmia
why does alcohol cause smooth muscle relaxation
- due to decreased vasomotor center + acetaldehyde
- vasodilation -> hypothermia (heat loss) + hypotension
- uterine relaxation
alcohol drug interactions
- additive CNS depression with other CNS depressants
- hepatic microsomal enzyme induction -> increased metabolism of drugs and generation of toxins, free radicles, H2O2
- drugs w disulfiram-like reaction (ex: metronidazole, trimethoprim)
what are long-term effects of alcohol consumption on the CNS
- tolerance, addiction, dependence
- neurotoxicity
alcohol tolerance
- may result from: ethanol-induced up-regulation of a pathway
- results in: decreased intensity, and shortened duration of action
- cross tolerance: sedative-hypnotics, general anesthetics
alcohol dependence
- psychological dependence:
- compulsion to: experience the rewarding effect, avoid the withdrawal sympt - physical dependence:
- withdrawal syndrome
mild: hyperexcitability
severe: seizures, psychosis, delirium tremens, coma, death
alcohol neurotoxicity
- peripheral neuropathy
what is wernicke-korsakoff syndrome
- caused by thiamine (vitamin B1) deficiency
- manifestations: extrinsic eye muscles paralysis, ataxia, confusion-encephalopathy-coma-death
- sequelae after treatment: korsakoff’s psychosis, memory loss, impaired vision
what are long term effects of alc consumption in the liver
alcoholic fatty liver, hepatitis, cirrhosis, liver failure
what are long term effects of alc consumption in the GI
- gastritis -> peptic ulcer and GI bleeding
- chronic pancreatitis
- malabsorption
- abnormal immune response
what are long term effects of alc consumption in the CVS
- cardiomyopathy and HF
- dysrhythmias - atrial and ventricular
- hypertension
- fetal alcohol spectrum disorders
what are hematologic long term effects of alc consumption
folic acid deficiency and decreased Fe anemia
what are long term effects of alc consumption in the endocrine and metabolic
- gynecomastia and testicular atrophy
- hypoglycemia
- lactic acidosis
what are cancerous long term effects of alc consumption
- mouth, pharynx, larynx, esophagus, liver
causes: acetaldehyde, folate metabolism changes, chronic inflammation
what is fetal alcohol spectrum disorder (FAS)
- conditions in children caused from chronic maternal alcohol abuse during preg
- mech of teratogenic effect: unknown!
- wide spectrum: most severe is fetal alc syndrome
- main manifestations: growth retardation, microcephaly, facial features, congenital heart defects, CNS defects
what are CNS defects in FAS
- cognitive deficits
- impaired motor function
- attention and hyperactivity problems (ADHD)
- social skills problems
- epilepsy
what are some treatments of acute intoxication
- prevent severe resp depression***
- aspiration of vomitus
- correct electrolyte imbalances
- treatment of hypoglycemia and ketoacidosis
- vitamin B1 (thiamine)
- no antidote
how to manage alcohol withdrawal syndrome
- mild sympt don’t need treatment
- prevention of seizures, delirium and dangerous dysrhythmias (vitamin B1, correct electrolytes, benzodiazepines)
best ways (4) to treat alcoholism
- rehab and psychological therapy
- naltrexone
- acamprosate
- disulfiram
what does naltrexone do
long acting opioid antagonist - blocks mu receptors
orally
help reduce craving
what does acamprosate do
decreases NMDA receptor and increases GABAa receptor
orally
help reduce craving
poorly absorbed from GIT
disulfiram
make pt hate drinking due to accumulation of acetaldehyde and all the effect of it
orally
precautions while using naltrexone
- pt should not be opioid dependent (opioid withdrawal)
- do not combine w disulfiram (both are hepatotoxic)
what is methanol (wood alc)
- uses: solvent, fuel, antifreeze
- absorption: GIT, skin, resp sys
- toxicity: due to formaldehyde & formate, causes visual disturbances, blindness, etc. use fomepizole or ethanol (antidotes) - IV
what is ethylene glycol
- polyhydric alcohol
- has a sweet taste
- uses: solvent, heat exchangers, antifreeze
what is ethylene toxicity
- due to: glycolaldehyde and oxalic acid
- effect: CNS excitation -> CNS depression -> anion gap metabolic acidosis -> renal and hepatic failure -> death
- treatment: fomepizole or ethanol (antidotes) - IV
