Alcohol Use Disorders Flashcards
MOA of benzodiazepines
bind to BZ-GABA-A receptor-> positive allosteric-> more Cl ion channel open-> treat withdrawal
Benzodiazepines decrease the duration and severity of symptoms and incidence of ___ and _______
seizures and delirium tremens
These can be experienced well past acute withdrawal
Which benzodiazepine is best for treatment of EtOH withdrawal? Which are the most used?
all are equal
-chlordiazepoxide, diazepam, lorazepam
Benzos should be dosed _______ for alcohol withdrawal than anxiety or insomnia
higher and more frequent
start high, taper slow
The most used barbiturate for alcohol withdrawal is
phenobarbital (oral, IM, IV)
Do barbiturates and benzodiazepines bind at the same place
no
Where to barbiturates bind and how is that used for alcohol withdrawal
subunits on GABA-A receptor complex-> (+) allosteric modulation-> Cl- open longer-> treated
Barbiturates suppresses _______ glutamate receptors and this _______
excitatory
decreases glutamate release
Barbiturates are useful as ____ and ____ when compared to benzos for AUD
first line and withdrawal refractory
Phenobarbital has a ___ onset of effect and a ____ half life
rapid, long
Phenobarbital should be ____ based doing. There is a concern for ____ _____.
weight based
respiratory depression
Phenobarbital should be used with caution in ___ and ____ disease. It is an enzyme ______
severe liver and renal disease
enzyme inducer
In addition to medications, what other things should be given to someone experiencing alcohol withdrawal
multivitamin, thiamine, folic acid, fluids (banana bag)
Likely you need more thiamine than what is in the banana bag
Giving thiamine to someone experiencing EtOH withdrawal can prevent ________. It needs to be given before or with ____.
Wenicke’s encephalopathy
D5W
Thiamine is converted to thiamine pyrophosphate which is a cofactor in ____
carbohydrate metabolism
Chronic drinking may present with alcoholic _____ and _____
ketacidosis and hypoglycemia
Alcohol interferes with hepatic _____ becasue _______
glyconeogenesis becasue the energy needed for alcohol metabolism is diverted away
Who is at greatest risk for alcoholic ketoacidosis and hypoglycemia
not eaten within 12-14 hours following last drink (N/V and loss of appetite)
Lorazepam is a great drug to use AUD because
long half life
few drug interactions (gluconoronidation)
PK are consistent through liver function
many methods of deliver
Alcohol withdrawal may present with___ and ____ which can lead to _______
HypoK and HypoMg
QT interval prolongation
Diazepam has a __ half life. What is special about its PK
long
active metabolites
Mg is a cofactor needed for converting ___ to ____
thiamine to thiamine pyrophosphate
For alcohol withdrawal, you can use ______ and ______ to treat sympathetic symptoms (BP, HR, tremor, sweating, anxiety_
clonidine and dexmedetomidine (“clonidine on steroids”, ICU IV only)
In the ED, the treatment is _______
symptom-triggered
Should you use anti seizure medications for alcohol withdrawal?
no, seizures usually end before administration of medication/benzodiazepines
Antipsychotics can be used to treat ____ and ____ in alcohol withdrawal. But there is a risk of ___ and ____
agitation, hallucinations
QTc prolong, lowering seizure threshold
Do not send a patient out of the hospital while they are still on _____
benzodiazepines
Three FDA approved medications for AUD
Two not FDA approved meds for AUD
disulfiram (Antabuse), naltrexone (and long acting vivitrol), acamprosate
Topiramate, gabapentin
_____ and _____ are first line for AUD treatment. if they do not respond to these two ______ is used
Naltrexone, acamprosate
Disulfiram
Disulfiram works as an alcohol ______ by _______ (MOA). There is ___ effect without alcohol
alcohol aversion medication
irreversibly inhibits aldehyde dehydrogenase-> acetaldehyde levels 5-10x normal.
no effect without alcohol, effect seen within 12-14 Horus of taking disulfiram
Alcohol + disulfiram = ?
palpitations, facial flushing, sweating, N/V, headache, tachycardia, chest pain, hypotension, dizziness, weakness
For disulfiram, caution when patients are also on/have:
metronidazole, cognitive disorder, unstable CVD, cirrhosis
Patients can be at risk for disulfiram reaction for ______ after stopping taking it
weeks
slow elimination and no aldehyde dehydrogenase needs to be synthsized
Disulfiram is pregnancy category __
C
Naltrexone is an antagonist at ____ which leads to a decrease in _____ in the reward pathway
mu-receptors, dopamine activity
this will lesses reinforcing properties of EtOH, decrease cravings, lesses intoxication feeling, lessens euphoria (uncouples drinking and pleasure)
What are the short term and long term effect of naltrexone?
Short term: reduce relapse, cravings, returning to drinking
long term: unclear if there is a benefit in maintaining abstinence
Naltrexone AE? Contraindications?
AE: N/V, somnolence
CI: opioids (7-10 days), child Pugh C liver dx, LFTs high (hepatotoxicity)
To prescribe naltrexone, need to order _____ and _____
urine too screen for opioids and LFTs (synthetic opioids will not show up)
Acamprosate modulates glutamate at _____ and is a _______ agonist.
NMDA, GABA-A receptor agonist
thought to restore equilibrium of GABA and glutamate systems
(toss up on if it actually works)
Acamprosate has a benefit in _______ and dosing is _____
maintenance of abstinence
weight based
Acamprosate AE? Contraindications?
AE: diarrhea
CI: CrCl<30ml/min
Use if worried about liver or pt on opioid or will continue to drink
For using acamprosate as a treatment for AUD, opioids, and liver dz: _______ are not a major concern. It is preg category ___.
drug drug
C
Treatment for AUD should continue for at least __ months
6
Clonidine and antipsychotics should be combined with ____ for alcohol withdrawal
benzodiazepine
What is considered heavy drinking
5 or more binge days a month (4 for female)
___ of EtOH is absorbed in the stomach, with the other amount absorbed in the small intestine
20%
If there is ______ there will be less EtOH absorbed
food in the stomach
Metabolism of EtOH
alcohol –alcohol dehydrogenase-> ______ –_______–> Acetic acid -> oxidation ->->-> energy (Krebs)
acetaldehyde
acetaldehyde dehydrogenase
Metabolism of EtOH
alcohol –alcohol dehydrogenase-> ______ –_______–> Acetic acid -> oxidation ->->-> energy
acetaldehyde
acetaldehyde dehydrogenase
EtOH elimination is ____ with time because of ___ saturation
linear, ADH saturation
you lose about 1 drink an hour
What are some reasons for the gender difference in alcohol disposition
women weight less, have more fat and less water, less gastric alcohol dehydrogenase (less first pass), eliminate slightly faster
What happens if you inhibit alcohol dehydrogenase or aldehyde dehydrogenase
You get nausea due to sympathetic NS activation-> bradykinin and His release-> nausea, flushing, hangover
Acetaldehyde dehydrogenase is an active ____ in the ____ of cells. There are mutations that cause it to have low affinity for ____ and as a result _______
tetramer in the mitochondria
low affinity for NAD, short half life with virtually no activity
EtOH inhibits toxic _____ ______ acutely due to inhibition of CYP2E1. However in chronic alcohol, there is CYP2E1 induction and if _____ is taken there will be:
acetominophen metabolism
acetaminophen, depletion of antioxidants and inactive conjugates leading to liver damage
What is the major MOA of EtOH in the brain
It is a GABA-A agonist and a glutamate (NMDA) antagonist
Typical sedating effects of EtOH
disinhibition, muscle relaxant, reinforcement, vasodilation, diuresis, sexual behavior
EtOH causes diuresis by _______
inhibition of ADH secretion
At what level of BAC will there be loss of motor coordination? What level is major impairment of mental and physical control? What level conscious but stupor? What level is lethal for 50%
0.08-0.10
0.14-0.16
0.3
.45
Consequences of regular binge drinking on major body organs
Brain-> memory, attention, exec function
Liver-> fatty liver, fibrosis, cirrosis
CV-> HTN, MI, stroke, atherosclerotic
Kidney-> glomerulonephritis
Cancer-> oral, pharynx, larynx, colorectal
Other-> pancreas, FAS, depression, impaired fertility
Main mechanism for alcohol tolerance
Decrease in GABA receptor function (internalization)
Increased NMDA function
(minor is metabolism change in liver)
Which things of alcohol withdrawal can be life threatening and should be treated with benzos
CNS hyper excitability, ANS hyper excitability, tremor and motor abnormalities
When alcohol releases β endorphins, inhibits GABA what gets released
dopamine
With tolerance to alcohol, there is enhanced ___ release which promotes GABA inhibition of DA release
glutamate
What causes Wenicke Korsakoff
thiamine deficiency
What causes encephalopathy
liver failure-> accumulation of ammonia
Mild deficits with alcohol will be seen with more than ___, moderate at ____ drinks/episode, substantial with 10 drinks/episode
5 drinks/episode
7-9
10 (6-7 days/week)
Brain damage from alcohol will cause increased _____ and loss of ______
increased ventricular space
loss of grey matter (dendrites and cell bodies
What is the process of hepatocytes turning into CT due to EtOH
Fatty liver with abnormal fat metabolism-> ROS + hepatic inflammation (alcoholic steahepatitis)-> alcoholic fibrosis from stellate cells making collagen-> liver failure
also 1-2% get hepatocellular carcinoma
What liver functions are lost with cirrhosis (there are 4)
blood clotting, albumin, growth and immune factors, drug and toxin metabolism
Sx of cirrhosis? (4)
hemorrhage, edema+ascites, immune dysfunction, decreased toxin removal
Acetaldehyde will cause ____ in blood vessels
fibrosis
EtOH can cause _____ due to disruption of potassium homeostasis
Arrhythmias
With modest alcohol consumption, what are some protective effects from EtOH
less atherosclerosis, stroke, PAD, decreased clotting, inflammation, increased plasminogen
Adolescents will have ____ sedation and motor impairment from alcohol. They suffer ____ memory loss
decreased
greater
(easier to continue drinking to high BAC)
What are some CNS dysfunction things caused by fetal alcohol spectrum disorder (behavioral + neuropsychological)
B: poor impulse, judgement, concentration and attention, fail to consider consequences
Neuro: trouble with math and reading, low IQ, poor exec fxn, short term memory problems, lack of social skills, visual spatial deficits
What is worse in FASD, binging or continual drinking?
binging
FASD: aspect of development at _______ determine outcomes
time of drinking
____ is an antibiotic that can also inhibit acetaldehyde dehydrogenase
Metronidazole
