Alcohol Flashcards
Where is alcohol dehydrogenase mainly found?
In the cytosol of cells in the liver and git
Alcohol dehydrogenase function
Metabolizes low to moderate doses of ethanol (into acetaldehyde)
Why does the alcohol dehydrogenase reaction exhibit 0 order kinetics
Because NAD+ is limiting
This means a constant amount of drug is eliminated per unit time
ALD1B*2 genetic polymorphism
Mutation in Alcohol Dehydrogenase
40-fold higher Vmax than ALD1B
Reduced risk of heavy drinking
They metabolize it so quickly so they have less chance of feeling euphoric effects, but more chance of converting to acetaldehyde which can be averting
How does acetaldehyde make you feel?
Nauseous, ill, sweating, trembling
ALDH2*2 genetic polymorphism
Non-functional aldehyde dehydrogenase
Homozygotes have a severe reaction
MEOS
Consists of cytochrome P450 2E1, 1A2 and 3A4
Uses NADPH as cofactor
Contributes to ethanol metabolism when ADH system is saturated
Chronic alcohol consumption induces MEOS
Which membrane proteins does alcohol affect?
GABAa receptors
Inhibits the activity of glutamate at NDMA receptors
Effects ATPases and adenyl cyclases (cell signalling)
Ion channels (like K ones)
3 steps in NMDAR activation
- Activation of non-NDMA receptors leads to cell depolarization
- Relieves NMDA receptors of Mg block
- Channel opens allowing cation entry
What causes blackouts?
Results from NMDA receptor blockade by ethanol
Not capable of forming new memories
4 things that influence blood levels of alcohol
Body size and build (lean muscle = more water = decreased effects) Gender (men have more lean muscle) General health (liver function) Food consumption (food slows absorption)
Metabolic consequences of alcohol (6)
Oxidative stress
Depletion of antioxidants like glutathione
Dysregulation of fatty acid oxidation and synthesis
Damage to mitochondria
Inflammation
Cytokine damage
2 serious effects of ethanol on the body
Myocardial contraction depressed
Vasodilation from depression of the vasomotor center in the CNS and direct actions on smooth muscle, which can lead to hypothermia
Effects of chronic alcohol consumption (5)
Liver function decreased Gluconeogensis reduced Hypoglycemia Fat accumulation in the liver (from depleted NAD+) CIrrhosis
Wernicke-Korsakoff syndrome is from…
Deficiencies in vitamin B1
What are the delirium tremens
Tachycardia Hypertension Low-grade fever Tremor Diaphoresis Delirum Agitation
What benzodiazepiene can you use to treat alcohol withdrawal?
Diazepam
Why do you use a benzo to help with alcohol withdrawal?
To lower the withdrawal severity and keep it below the seizure threshold
Disulfiram
Used to manage alcohol addiction
Can take it every day, no effects without alcohol
Causes extreme discomfort when alcohol is consumed
Flushing, headache, nausea, vomiting, sweating, hypotension and confusion
Binds to an inactivates aldehyde dehydrogenase
Naltrexone
Will get abstinence in every 1 out of 10 people that you treat and significant reduction in everyone else
Functions as a competitive antagonist at opioid receptors and exhibits the highest affinity for the mu receptor isoform
Ethanol and beta endorphins
Ethanol promotes beta endorphin release in regions of the brain involved in reward
Central effects are mediated through mu opioid receptors
Beta endorphins can directly stimulate dopamine release in the nucleus accumbens
Acamprosate
Alters the activity of NMDA receptors
Highly dose dependent
Can lessen withdrawal and cravings
Gabapentin and alcohol
Normalizes the stress-induced GABA activation in the amygdala that is associated with alcohol dependence
Methanol poisoning
Can cause visual disturbances
Toxicity is related to build up of formaldehyde and formate (occurs slowly)
Can lead to bradycardia, coma, seizures, and cessation of respiration
Ethylene Glycol poisoning
Antifreeze
Toxicity is related to build up of oxalate and other metabolites which can occur slowly
2 inhibitors of ADH
Fomepizole
Ethanol
Can be used to treat ethylene glycol poisoning
