Alcohol: use and abuse

Question 1

What are antidotes for alcohol intox?

Answer 1

time and fluids

Question 2

Drugs for chronic alcoholics

Answer 2

naltrexone, acamprosate

Question 3

Drugs for ethanol withdrawal

Answer 3

diazepam, thiamine (if deficient)

Question 4

What are the antidotes for acute methanol and ethylene glycol intoxication

Answer 4

ethanol, fomepizole

Question 5

Explain alcohol metabolism

Answer 5

alcohol–> alcohol dehydrogenase –> acetaldehyde –> aldehyde dehydrogenase –> acetate

Question 6

What type of metabolism does ethanol go through?

Answer 6

zero order (as does phenytoin and high-dose of aspirin

Question 7

Where does ethanol metabolism take place?

Answer 7

Liver

Question 8

What is the CYP involvement in ethanol metabolism?

Answer 8

Very little CYP involvement under normal circumstances

-chronic alcoholism: may be more due to induction

Question 9

What is the MOA of disulfiram as alcohol is concerned?

Answer 9

Used to encourage abstinence from alcohol by preventing the metabolism of acetaldehyde –> accumulation –> nausea and flushing reaction of the skin

Question 10

what happens to asians when they drink? Why?

Answer 10

Asian flush due to decreased aldehydrogenase enzyme: build up of acetaldehyde –> skin flushing reaction

Question 11

How can acetaldehyde affect the VTA?

Answer 11

In some patients it can act on the pleasure center in the VTA, increasing pleasure and leading to reinforcement of alcohol seeking behavior
*Maybe Native Americans

Question 12

What CYP does ethanol affect?

Answer 12

CYP2E1

*potential for ethanol to alter metabolism of concurrent drugs – acetaminophen

Question 13

What is significant about acetaminophen metabolism in chronic alcoholism?

Answer 13

usually only slightly metabolized to NAPQ1. When chronic alcoholics have CYP2E1 inductions more is metabolized to NAPQ1 –> depletion of glutathione (normally detoxifies NAPQ1–> hepatotoxicity

Question 14

What antidote can be given for aspirin overdose in a chronic alcoholic

Answer 14

N-acetylcysteine (replenished glutathione store)

Question 15

How does alcohol effect the GABA system?

Answer 15

increases GABA release and increases receptor density

Question 16

How does alcohol effect the NMDA system?

Answer 16

inhibits postsynaptic NMDA receptors, with chronic use –> up-regulation

Question 17

How does alcohol effect the DA system?

Answer 17

increases synaptic DA, increases effects on ventral tegmentum/ nucleus accumbens reward

Question 18

How does alcohol effect the ACTH system?

Answer 18

increases CNS and blood levels of ACTH

Question 19

How does alcohol effect the opioid system?

Answer 19

release of beta-endorphins and activation of mu receptors

Question 20

How does alcohol effect the 5-HT system?

Answer 20

increases in 5-HT synaptic space

Question 21

How does alcohol effect the cannabinoid system?

Answer 21

increases CB1 activity –> changes in DA, GABA, and glutamate activity

Question 22

What causes “black-outs”

Answer 22

inhibition of the stimulatory actions of the glutamate system

Question 23

How does alcohol effect the CV system?

Answer 23

CV depressant

• HTN, anemia, dilated cardiomyopathy
• arrhythmias with binge drinking (acutely high BAL)
• increased HDL (modest alcohol drinking)-> protective against CHD

Question 24

How does alcohol effect smooth muscle?

Answer 24

Vascular SM: relaxtion, vasodilation –> possible hypothermia, increased gastric blood flow
Uterine SM: relaxes it, slows/stops contractions

Question 25

What determines BAL?

Answer 25

body makeup of the drinker - distributes within total body water - does not distribute into adipose tissue (more fat, higher BAC) - females: higher BAL than males

Question 26

What are the chronic effects of alcohol on the liver?

Answer 26

- decreased gluconeogenesis --> hypoglycemia | - fatty liver --> hepatitis, cirrhosis, liver failure

Question 27

What are the chronic effects of alcohol on the GI tract?

Answer 27

bleeding --> scarring --> absorptive problems and nutritional deficiency

Question 28

What are the chronic effects of alcohol on the CNS?

Answer 28

- peripheral neuropathy | - Wernicke-Korsakoff syndrome= ataxia, confusion, ocular muscle paralysis

Question 29

How is Wernike-Korsakoff treated?

Answer 29

thiamine

Question 30

What are the chronic effects of alcohol on the endocrine system?

Answer 30

-decreased synthesis of corticosteroids --> gynecomastia, testicular atrophy (steroid insuff)

Question 31

What is the result of thiamine deficiency?

Answer 31

inability to synthesize and replenish critical amino acids and proteins (especially in CNS)

Question 32

How is thiamine usually administered?

Answer 32

IV or IM injection, some may be treated orally

Question 33

What cancer incidence increases with alcohol consuption

Answer 33

GI cancer

Question 34

How is the immune system effected by alcohol?

Answer 34

enhanced inflammation in the liver and pancreas, but reduced immune response in other tissues **chronic alcoholics are susceptible to infectious pneumonia

Question 35

Does alcohol cross the placenta?

Answer 35

yep

Question 36

How do fetal blood alcohol levels compare to the maternal blood alcohol levels?

Answer 36

fetal levels reflect the mother's levels

Question 37

What does alcohol cause in the fetus?

Answer 37

apoptosis and incorrect neuronal and glial migration in the developing nervous system

Question 38

What features characterize fetal alcohol syndrome?

Answer 38

- intrauterine growth retardation - microcephaly - poor coordination - midfacial underdevelopment (flattened face) - minor joint anomalies - some congenital heart defects - subtle neurologic deficits

Question 39

During what trimester is alcohol more damaging to the fetus?

Answer 39

1st trimester, but problems can still arise with alcohol consumption in the 3rd trimester

Question 40

What therapy is given to an intoxicated patient in the ED?

Answer 40

- ABCs - dextrose (if low sugar) - thiamine (protect against W-K syndrome) - correct electrolytes * * give thiamine before dextrose (can exacerbate W-K)

Question 41

What therapy is given to a patient suffering from alcohol withdrawal in the ED?

Answer 41

- BNZ sedative - --usu long acting diazepam, with hepatic probs: lorazepam - thiamine - correct electrolytes

Question 42

What does a person with alcohol withdrawal present like?

Answer 42

insomnia, tremor, anxiety, N?V diarrhea, arrhythmias | *rarely seizures

Question 43

Why would lorazepam be used instead of diazepam in a patient with alcohol withdrawal?

Answer 43

Lorazepam is metabolized through glucuronidation and is better in patients with liver disease

Question 44

What pharmacokinetic changes can be seen when alcohol is used with other drugs?

Answer 44

increased teratogenicity, increased absorption of either or both

Question 45

What pharmacokinetic changes can be seen when alcohol is used with other drugs?

Answer 45

- additive CNS depressive actions with drugs - increases toxicity of acetaminophen - increased risk of bleeding with NSAIDs and anticoags - increased risk of hypoglycemia in diabetics on medication - Disulfiram effects

Question 46

What are disulfiram effects, and what are some examples that cause this?

Answer 46

Have the ability to increase acetaldehyde when taken with alcohol *sulfonylureas, cefotetan, ketoconazole, procarbazine

Question 47

What is the MOA of naltrexone?

Answer 47

mu opioid antagonist, felt to decrease drinking though decreased feelings of reward with alcohol and/or decreased craving

Question 48

What is the MOA of acamprosate?

Answer 48

weak NMDA antagonist, activator of GABA receptors, may decrease mild protracted abstinence syndroms with decreased feeling of "need" for alcohol

Question 49

What two nuclei are involved in the reward pathway effect of alcohol?

Answer 49

VTA and NA | ventral tegmental area and nucleus accumbens

Question 50

What neurotransmitters are involved in the indirect activation of the reward pathway activated by alcohol?

Answer 50

serotonin, ACh, opioids, GABA, glutamate

Question 51

What is the cause of alcohol withdrawal symptoms within the CNS?

Answer 51

with chronic use, many neurochemical systems undergo adaptations and attempt to reach homeostasis, so when alcohol is withdrawn homeostasis is effected

Question 52

How is ethylene glycol metabolized?

Answer 52

ethylene glycol --> via alcohol dehydrogenase --> oxalic acid --> acidosis and nephrotoxicity

Question 53

How is methanol metabolized?

Answer 53

methanol --> via alcohol dehydrogenase --> formaldehyde, formic acid --> severe acidosis, retinal damage

Question 54

What is the MOA of fomepizole?

Answer 54

competative inhibitor of alcohol dehydrogenase - IV infusion * can prevent optic neuropathy

Question 55

How is ethanol effective as a way to stop methanol and ethylene glycol intoxication?

Answer 55

Acts as a competitive inhibitor to saturate alcohol dehydrogenase (maintain BAL at 100 mg/dL) **saturation of enzyme is effective because it is zero-order

Question 56

What are ways unabsorbed alcohol can be decontaminated?

Answer 56

induced emesis, gastric intubation or suction, administration of adsorbent charcoal --> reduces systemization of poison

Question 57

What is the MOA of acamprosate?

Answer 57

GABA agonist: works between the VTA and NA affecting reward pathway