1- Alcohol

Question 1

What is the most psychoactive drug in the US?

Answer 1

Alcohol

Question 2

How is alcohol abuse defined?

Answer 2

Social life impaired for at least 1 month

Question 3

How is alcoholism defined?

Answer 3

Prolonged alcohol use leading to tolerance and dependence (also continuous or periodic lack of control over drinking, preoccupation with alcohol, use of alcohol despite adverse consequences, and distortions in thinking (especially denial))

Question 4

How does genetic predisposition contribute to alcoholism?

Answer 4

Increased release of beta-endorphins in dopamine reward pathway

Question 5

What are the MOAs of alcohol? (4)

Answer 5

1. CNS depressant
2. Binds to/ enhances inhibitory GABA transmission
3. Increases dopamine in mesolimbic pathway
4. Inhibits effects of glutamate on NMDA receptor

Question 6

Do plasma levels of alcohol change in pharmacokinetics or pharmacodynamics?

Answer 6

Pharmacokinetics (pharmacodynamics = plasma levels NOT changing but body is changing)

Question 7

What parts of the body is alcohol absorbed from?

Answer 7

Stomach and small intestine

Question 8

When does BAC peak?

Answer 8

Within 30-90 min after last drink

Question 9

What 2 things does alcohol cross?

Answer 9

BBB and placenta

Question 10

Chronic alcohol use can lead to up and down regulation of what?

Answer 10

Down regulation of GABA receptors Up regulation of NMDA receptors

Question 11

Chronic alcohol use is associated with cross tolerance with what 2 drug classes?

Answer 11

Benzodiazepines and barbiturates (due to both binding to GABA receptors)

Question 12

What order kinetics does alcohol display?

Answer 12

Zero order (metabolism rate independent of concentration)

Question 13

What metabolizes alcohol? (2)

Answer 13

ADH > MEOS/CY2E1

Question 14

What is the metabolism pathway of alcohol? (3 steps)

Answer 14

Alcohol → acetaldehyde (via ADH) → acetate (via ALDH, requires NAD+)

Question 15

How does an ALDH deficiency affect alcohol metabolism?

Answer 15

Metabolize alcohol more slowly (women have lower ALDH levels)

Question 16

What is the MOA of Disulfiram?

Answer 16

Inhibits aldehyde dehydrogenase (ALDH)

Question 17

How are MEOS/ CYP450s and CYP2E1 affected by chronic ethanol consumption?

Answer 17

Induced by chronic ethanol consumption (→ increased ethanol metabolism → need more alcohol to get drunk)

Question 18

Alcohol + Acetaminophen can lead to what?

Answer 18

Liver damage

Question 19

How does alcohol interact with phenytoin and oral hypoglycemic agents?

Answer 19

Increases metabolism

Question 20

How does alcohol interact with benzodiazepines, barbiturates, phenothiazines and tricyclic antidepressants (TCAs)?

Answer 20

Synergistic CNS depression

Question 21

What are the effects of alcohol at low levels?

Answer 21

Disinhibition

Question 22

When does alcohol cause impaired motor function and judgement, CNS depression/ sedative effects, anterograde amnesia (blockade of NMDA receptors)?

Answer 22

Higher doses

Question 23

What can alcohol toxicity result in? (4)

Answer 23

Emesis, coma, respiratory distress, death

Question 24

Alcohol exhibits effects on what system as a vasodilator resulting in hypothermia and uterus relaxation (can prevent preterm labor)?

Answer 24

Smooth muscle

Question 25

How does alcohol affect the heart?

Answer 25

↓ contractility (↓ CO/BP)

Question 26

How does alcohol affect the kidney?

Answer 26

↓ ADH → diuretic effect

Question 27

How is alcohol toxicity managed? (2)

Answer 27

Manage respiratory depression and prevent emesis

Question 28

If a pt with alcohol toxicity is having seizures, what is the treatment?

Answer 28

Lorazepam (benzo) and Phenytoin (anticonvulsant)

Question 29

What is the main cause of a hangover (in addition to dehydration and beginning of withdrawal)?

Answer 29

Buildup of acetaldehyde

Question 30

What is the general cause of the complications seen with chronic alcohol use/ alcohol tolerance?

Answer 30

Decreased glutathione concentrations = oxidative stress and tissue damage

Question 31

What are the 3 most common complications associated with chronic alcohol use?

Answer 31

Gastritis, pancreatitis, **liver disease**

Question 32

What are the most common liver complications associated with chronic alcohol use? (3)

Answer 32

* Alcoholic hepatitis * Liver cancer- most likely 10 yrs after stopping alcohol consumption due to liver attempting to heal itself * Fatty liver → fibrosis → cirrhosis

Question 33

Chronic alcohol use leads to malnutrition specifically related to what 2 things?

Answer 33

Folate and thiamine

Question 34

What CNS complication of chronic alcohol use is defined as a thiamine deficiency leading to paralysis of eye muscles, ataxia, confusion, coma/ death?

Answer 34

Wernicke-Korsakoff syndrome

Question 35

What CNS complication of chronic alcohol use is defined as chronic disabling memory loss?

Answer 35

Korsakoff's psychosis

Question 36

Aside from Wernicke-Korsakoff syndrome and Korsakoff's psychosis, what other CNS complication can be associated with chronic alcohol use?

Answer 36

Peripheral neuropathy

Question 37

What are the most common CV complications seen with chronic alcohol use? (5)

Answer 37

Cardiomyopathy (toxic effects of acetaldehyde), arrhythmias, HTN, stroke, CHD

Question 38

How does alcohol affect tobacco use?

Answer 38

Increases carcinogenicity

Question 39

The following are associated complications of what? Mild anemia, sexual dysfunction, immune system suppression, skeletal muscle atrophy, hypothermia, teratogenicity

Answer 39

Chronic alcohol use

Question 40

What is the most effective treatment for alcohol abuse?

Answer 40

Combo of pharm and psychosocial

Question 41

What is the MOA for Naltrexone? (3)

Answer 41

Opioid receptor antagonist → blocks ability of alcohol to stimulate reward pathway → reduces cravings & relapse

Question 42

What is the contraindication for Naltrexone?

Answer 42

Liver failure

Question 43

What is the MOA for Acamprosate? (3)

Answer 43

Structural analogue of GABA → restores normal balance of GABA and glutamate → decreases cravings and relapse

Question 44

How is Acamprosate excreted?

Answer 44

By kidneys (no liver toxicity)

Question 45

When should Disulfiram be taken to be effective?

Answer 45

Prior to alcohol consumption

Question 46

What is the action of Disulfiram? (3)

Answer 46

Inhibits aldehyde dehydrogenase → acetaldehyde builds up → flushing, HA, nausea, confusion (makes drinking alcohol unenjoyable)

Question 47

Does Disulfiram have a long or short duration of action?

Answer 47

Long

Question 48

What are the **severe** effects of Disulfiram? (7)

Answer 48

Vomiting, sweating, chest pain, hypotension, vertigo, blurred vision, shock (dangerous and not recommended)

Question 49

What is the MOA for Topiramate?

Answer 49

Anticonvulsant (alcohol role not well understood)

Question 50

What is the effect of Topiramate?

Answer 50

Decreases craving and increases abstinence in recovering alcoholics

Question 51

The following are sxs associated with what? Anxiety, irritability, nausea, tachycardia, insomnia

Answer 51

Mild alcohol withdrawal

Question 52

The following are sxs associated with what? Hallucinations, delirium, tremors, seizures, fatal arrhythmias, hypotension

Answer 52

Severe alcohol withdrawal

Question 53

What is the general treatment for alcohol withdrawal? (non-pharmacologic)

Answer 53

Restore electrolyte imbalances, hydration

Question 54

What do Diazepam (Valium) and chlordiazepoxide do with respect to treatment of alcohol withdrawal?

Answer 54

Prevent seizures and delirium/ tremors, tapers sxs

Question 55

What does Lorazepam (Ativan) do with respect to treatment of alcohol withdrawal?

Answer 55

Used to TREAT seizures

Question 56

What does Phenytoin (Dilantin) do with respect to treatment of alcohol withdrawal?

Answer 56

Secondary drug to TREAT seizures