Sweatman - Alcohol Flashcards
1
Q
Which metabolic pathway is depleted in a chronic alcoholic?
A
- Mercapturic acid conjugation
2
Q
Disheveled man is confused, stuporous, and ataxic, with occasional nystagmus. What drug is indicated in initial pt mgmt?
A
- Thiamine
- Classic triad only seen in about 15-20% of pts, and may be difficult to differentiate from person that is “just” intoxicated
3
Q
Young man with 380mg/dL. How would you characterize his presentation?
A
- Comatose
- NOTE: the body can adapt to the presence of alcohol -> 2 cases presented in class where people had VERY high BAC, and were “ok”
4
Q
How can you extend the action of Naltrexone?
A
- Can give it by depot injection, assuring pt has taken it, and it lasts a longer period of time
- NOTE: Acamprosate must be taken 3x/d PO, so much more likely to have trouble with adherence
5
Q
How does alcohol act in the brain? Where?
A
- Thought to stimulate endogenous opioid peptides and GABA activity in the VENTRAL TEGMENTAL AREA (VTA) and INH release of excitatory glutamate from NN terminals that act on neurons in NUCLEUS ACCUMBENS -> reward system (also affects serotonin, Ach levels)
- These actions ENHANCE DOPAMINERGIC TRANSMISSION in the cortico-mesolimbic pathway
- Repeated exposure to alcohol over time leads to adaptation to these effects
- When alcohol is withdrawn, these systems undergo adaptations and attempt to achieve homeostasis, leading to withdrawal symptoms and consumption of alcohol for negative reinforcement, or avoidance of withdrawal
- Most meds for alcoholism act on these NT systems, and are focused on normalizing the alcohol-specific neuroadaptations or blocking alcohol-specific reinforcement
- NOTE: these are the areas of the brain involved in the response to addictive drugs
6
Q
What might an alcoholic who is unable to secure quantities of ethanol drink?
A
- Methanol
- Ethylene glycol (antifreeze)
- NOTE: these alternative agents are metabolized to toxic products that can produce permanent damage
7
Q
How do you tx methanol/ethylene glycol toxicity?
A
- Prevention of their metabolism is accomplished via admin of: Ethanol or Fomepizole
8
Q
What drugs are available to tx alcohol dependency? Where do they act?
A
- Disulfiram
- Naltrexone: VTA
- Acamprosate: NA
- NOTE: alcohol is an addictive drug to which those who consume it on a chronic bases become dependent
9
Q
How might alcohol withdrawal present in the ED? Tx?
A
- These pts may be malnourished and have vitamin deficiencies
- Can also be agitated
- May admin thiamine and/or BNZ
10
Q
Describe the metabolism of ethanol.
A
- Takes place primarily in the liver; 2 enzyme systems may be involved
- Ethanol -> alcohol dehydrogenase -> acetaldehyde -> aldehyde dehydrogenase -> acetate
- Under normal circumstances, very little involvement of CYP metabolism in processing of ethanol, but in CHRONIC ALCOHOLIC, enzyme induction may occur
- NOTE: this is a zero-order process, so the enzymes involved in metabolism are saturated, and performing at maximum capacity
11
Q
What is Disulfiram? MOA?
A
- Drug used to encourage abstinence from alcohol by preventing metabolism of acetaldehyde (by INH acetaldehyde dehydrogenase)
- Leads to accumulation of this normally transient intermediate
- Accumulation of acetaldehyde gives rise to a feeling of NAUSEA and FLUSHING reaction of the skin -> these adverse effects are intended to prevent alcoholics from drinking in the first place
- NOTE: some alcoholics fear a potentially fatal reaction (probably a fear arising from much larger doses given in the past -> no long-term effects if alcohol is consumed)
12
Q
Why does “Asian flush” happen?
A
- Common SNP in aldehyde dehydrogenase in Asian ppl yields diminished functional capacity of the enzyme
- ALDH21/22 heterozygosity -> more (+) feelings after alcohol intoxication
- Associated with lower prevalence of abuse and alcoholism
- May manifest an extreme flushing reaction in the skin with even a minimal amount of alcohol consumption
- NOTE: acetaldehyde effects may explain alcoholism prevalence among Native Americans
13
Q
What is ironic about acetaldehyde?
A
- Some alcoholics find it to be pleasurable -> appears to provide a dual action:
- Unpleasant in the periphery
- Pleasurable in the VTA, where it promotes DA release and appropriate levels may give rise to a reinforcement of alcohol-seeking behavior
- Condenses with DA to produce SALSOLINOL, a strongly reinforcing agent
14
Q
How does alcoholism affect tylenol metabolism? Antidote?
A
- While CYP450 is not a major player in the metabolism of ethanol, ethanol is an important INDUCER of CYP2E1
- Acetaminophen is normally conjugated with a sulfate or to a glucuronide, with little involvement in other metabolic processing
- What little is left of acetaminophen is converted through a highly reactive intermediate, NAPQI, which is rapidly conjugated and detoxified
- In CHRONIC ALCOHOLICS who have induced CYP2E1, there is a dramatic INC in the rate and extent of conversion to NAPQI
- Available stores of conjugate substrate (glutathione) to detoxify this reactive intermediate become depleted, and accumulation of NAPQI in the liver leads to significant HEPATOTOXICITY
- ANTIDOTE is N-ACETYLCYSTEINE, which provides fresh conjugate substrate for reactive intermediate to be safely detoxified
15
Q
What are the physiological effects of alcohol at each BAL range?
A
- 0 = collection in tiger top or red top tube (don’t use alcohol wipe; use povidone-iodine)
- 400 = coma -> if untreated, death will ensue from respiratory depression
- NOTE: ethanol produces effects primarily in the CNS, and consequences vary by level of alcohol produced
