Block 2: Alcohol/alcoholism

Front 1

Most widely used centrally acting drug known to man and a widely used industrial solvent?

Back 1

ethanol

Front 2

How high can yeast fermentation levels of ethanol reach?

Back 2

15%; get higher percentage with distillation

Front 3

3 special physical properties?

Back 3

1. infinitely soluble in polar and non-polar solvents
2. low molecular weight
3. cannot be ionized

Front 4

commercial beers
wines
fortified wines (sherry...)
distilled spirits

What is the percent ethanol?

Back 4

4%-10%
11%-14%
14%-20%
30%-60%

Front 5

How much ethanol is usually consumed in a standard drink

Back 5

10-15g

Front 6

What water compartment is alcohol distributed to?

Back 6

total body water
--> approx blood level by ingested dose and weight

Front 7

How is it absorbed?

Back 7

most in duodenum
a lot in stomach
-gastric emptying may be rate-limiting

Front 8

Why are blood levels higher in women than in men following an equal dose

Back 8

some metabolism by dehydrogenase in stomach wall in males, less in females

Front 9

Over 90% of ingested ethanol is eliminated by metabolism in the ...

Back 9

liver

Front 10

Major metabolic pathway

Back 10

alcohol --> oxidation by ADH (w/ NAD)--> acetaldehyde --> oxidation by aldehyde dehydrogenase (w/ NAD) --> acetate

Front 11

Minor metabolic pathway

Back 11

CYP450 (CYP2E1) --> acetaldehyde
acute exposure slows metabolism of other drugs metabolized by CYP2E1; chronic exposure inc CYP2E1

Front 12

What happens to the acetate?

Back 12

converted to Acetyl CoA --> citric acid cycle (w/ CoA and ATP) --> CO2, H2O, and CALORIES!

Front 13

What is the maximum rate of ethanol oxidation by alcohol dehydrogenase limited by?

Back 13

NAD

Front 14

What type of kinetics is exhibited?

Back 14

zero-order (at blood levels excess of .1 mg/ml)
--> constant amt of ethanol eliminated per unit time (rather than constant fraction)

Front 15

What is the average metabolic rate?

Back 15

7 grams.hour
(one shot takes 2 hrs to be cleared)

Front 16

What inhibits Alcohol dehydrogenase?

Back 16

fomeprazole

Front 17

What is fomeprazole?

Back 17

a drug used to delay metabolism of toxic alcohols (methanol, ethylene glycol) that have toxic metabolites

Front 18

Is ethanol a strong drug?

Back 18

no, it's weak--> many grams must be taken to induce an effect --> places heavy burdern on elimination system

Front 19

Ethanol metabolism alters redox potential from inc NADH:NAD ratio, what are the effects of reduced NAD?

Back 19

fatty acid synthesis inc
fatty acid oxidation dec
plasma FFAs inc
TG accumulate in liver
(all at low non-intoxicating levels)

Front 20

What does ethanol do to the GI tract?

Back 20

stimulates gastric acid secretion--> pain in peptic ulcers, inc ulcer formation

Front 21

Ethanol causes peripheral vasoconstriction or vasodilation?

Back 21

dilation --> flushing, feel warm --> loose body heat --> hypothermia in cold weather

Front 22

What does the vasodilation do to the sympathetic nervous system?

Back 22

causes tachycardia

Front 23

what are heart benefits of low doses of ethanol?

Back 23

cardioprotective from dec LDL
reduces risk of ischemic (not hemorrhagic) stroke

Front 24

What is the primary pharmacodynamic effect of ethanol and how is manifested?

Back 24

CNS depression; intoxication

Front 25

What causes the euphoria?

Back 25

inc release of DA (by disinhibition) in nucleus accumbens --> activates "reward" pathways --> drives further ethanol consumption

Front 26

What is the legal limit to drive in most states?

Back 26

1 mg/mL (~20 mM)- CNS effects are related to blood concentrations

Front 27

What does ethanol do to ADH

Back 27

inhibits it by inhibiting supraoptic and paraventricular neurons in hypothalamus --> diuresis, dehydration

Front 28

What does ethanol do to LHRH?

Back 28

acts at cannabinoid CB-1 receptors --> release of endocannabinoids --> dec LHRH release in hypothalamus --> dec reproductive function

Front 29

What is the mechanism of action of ethanol?

Back 29

disrupts neuronal membrane receptors and dec firing
1. inhibits glutamate NMDA activated Ca current --> dec synaptic transmission
2. potentiates GABA mediated inc in Cl conductance
3. enhances sedative effects of adenosine at A1 receptors

Front 30

mild euphoria
increased reaction time
impaired judgement
increased risk of accident

Back 30

below 1 mg/mL

Front 31

irregular gait
ataxia
confusion
slurred speech
elation/euphoria w/ impaired cognition
sedation

Back 31

1-2 mg/mL

Front 32

emesis
stupor/severe sedation
anesthesia
respiratory depression

Back 32

2-4 mg/mL

Front 33

coma

Back 33

4-5 mg/mL

Front 34

death by respiratory depression

Back 34

>5 mg/mL

Front 35

5 ways to manage acute ethanol intoxication?
What should you avoid?

Back 35

1. gastric lavage
2. maintain cardiopulmonary status, temp, acid-base
3. fluids for dehydration
4. antacid or histamine H2 antagonist to dec gastric irritation
5. thiamine and glucose

avoid tx w/ stimulants or other CNS depressants

Front 36

What can cause extreme toxicity, metabolic acidosis, blindness and death in large quantities?

Back 36

methanol

Front 37

How is methanol metabolized?

Back 37

methanol --> oxidation by alcohol dehydrogenase (w/ NAD) --> formaldehyde

Front 38

What causes the blindness w/ methanol?

Back 38

formaldehyde at retina (high local activity of retinol dehydrogenase)

Front 39

What causes the methanol acidosis?

Back 39

formic acid formation from formaldehyde

Front 40

How do you treat methanol poisoning?

Back 40

1. support if depression present
2. correct acidosis
3. give ethanol or fomeprazole to retard formation of formaldehyde

Front 41

Are higher alcohols more or less potent than ethanol as CNS depressants?

Back 41

more

Front 42

How does anti-freeze work towards intoxication

Back 42

ethylene glycol is potent CNS depressant
1. oxidation product glycoaldehyde is toxic to kidney -> renal failure and death from uremia
2. secondary product glycolic acid -> metabolic acidosis

Front 43

How do you treat ethylene glycol poisoning?

Back 43

fomeprazole

Front 44

How much alcohol is assoc with significantly reduced risk of cardiac infarction for men?

Back 44

1-2 drinks per day; 3-7 drinks per week

Front 45

What was the result of the randomized trial conducted to show reduction in CV disease with moderate daily alcohol intake?

Back 45

no such trial

Front 46

What is chronic alcohol use associated with

Back 46

inc hypertension
cardiac arrhythmias
stroke

Front 47

Give an operational definition of alcoholism

Back 47

continued consumption is necessary to prevent onset of withdrawal sx

Front 48

Is the dependence physiological or psychological?

Back 48

both

Front 49

How much of the US suffers from alcoholism

Back 49

at least 2%

Front 50

Are persons who are relatively insensitive to the intoxicating actions of alcohols more or less likely to become alcoholics than highly sensitive persons

Back 50

more likely

Front 51

bouts of severe intoxication for 1-4 days; abstinence for days

Back 51

binge drinker

Front 52

continuous slow rate of consumption; rarely wildly intoxicated; seldom abstinent for more than a few hours

Back 52

continuous drinkers

Front 53

What contributes to tolerance?

Back 53

partly metabolic; also adaptations in CNS pathways

Front 54

alcohol induces CYP450 enzymes- how does metabolism in alcoholics differ?

Back 54

up to 50% of ethanol may be metabolized by CYP2E1; inc metabolism

Front 55

How does metabolism of other drugs that use CYP450 enzymes differ in alcoholics?

Back 55

abstinent alcoholic- inc metabolism of those drugs
presence of alcohol- dec metabolism of those drugs

Front 56

What is pharmacodynamic tolerance?
Cross tolerance w/?
Less tolerance to?

Back 56

dose necessary to produce intoxication increases with constant use; cross tolerance with other CNS depressants (barbituates; general anesthetics; less tolerance to acute lethal effects)

Front 57

How long do the true withrdawal sx (abstinence syndrome) last upon cessation of alcohol consumption by alcoholics?

Back 57

start at 12-24 hrs after last drink; last 5-7 days

Front 58

What sx are included in withdrawal?

Back 58

tremors; hyper-reflexia; sweating; muscle cramps; vomiting
visual hallucinations, delirium tremens (DT's)
hyperthermia, CV collapse
Grand Mal seizures

Front 59

When do DTs usually show up?

Back 59

day 3 or 4

Front 60

Name other neural effects of chronic ethanol

Back 60

1. peripheral neuropathy, pellagra: paresthesia, dec DTRs
2. Wernicke's encephalopathy
3. Korsakoff's psychosis
4. Cerebellar degeneration

Front 61

nicotinic acid deficiency

Back 61

pellagra

Front 62

thiamine deficiency

Back 62

Wernicke's encephalopathy

Front 63

partial paralysis of eye movements
nystagmus
ataxia
disorientation

Back 63

Wernicke's encephalopathy

Front 64

memory loss
confusion
confabulation

Back 64

Korsakoff's psychosis

Front 65

ataxia and intention tremor

Back 65

cerebellar degeneration

Front 66

What does chronic ethanol exposure do to the liver

Back 66

1. fat accumulation
2. acetaldehyde accumulation
3. induces CYP2E1
--> necoris and fibrosis --> cirrhosis --> liver failure

Front 67

What does acetaldehyde do in the liver?

Back 67

1. inc lipid peroxidation
2. damages mito and cell membranes
3. depletes glutathione
4. depletes vitamins and metals
5. dec transport and secretion of proteins

Front 68

Why is heavy drinking associated with decreased appetite?

Back 68

high caloric content

Front 69

How does ethanol cause pancreatitis?

Back 69

pancreatic hypersecretion

Front 70

Acute ethanol drug interactions?

Back 70

inhibits metabolism of drugs by P450

Front 71

chronic ethanol drug interactions?

Back 71

induces CYP2E1 --> inc metabolism of acetaminophen (--> hepatotoxic metabolites), halothane

Front 72

How sure are we that maternal consumption of ethanol during pregnancy is teratogenic?

Back 72

unequivocally associated

Front 73

Name some effects of fetal alcohol syndrome

Back 73

small head circumference
low IQ
low body weight
impaired immune system

Front 74

Is fetal alcohol syndrome dose dependent?

Back 74

heavy drinking is required for full syndrome, but even lower levels result in significant effects on brain and body development

Front 75

How do you treat alcohol withdrawal syndrome?

Back 75

1. benzodiazepine (diazepam) to dec seizures
may use lorazepam or diazepam i.v.
may use carbamazepine for seizures
2. fluid and electrolyte supplementation w/ vitamins

Front 76

Name 3 pharmacologic approaches to maintain alcohol free state in alcoholics

Back 76

disulfiram (antabuse)
naltrexone
acaprosate

Front 77

inhibits aldehyde dehydrogenase -> acetaldehyde accumulation -> cutaneous vasodilation, nausea, vomiting, syncope (from hypotension), misery
sometimes hepatitis

Back 77

antabuse

Front 78

Which should only be used in conjunction with counseling?

Back 78

antabuse- aversion therapy

Front 79

an opiate antagonist, reduces reinforcing effects of ethanol; dec relapses

Back 79

naltrexone

Front 80

NMDA and GABA-A receptor modulator; reduces unpleasentness of abstinence, reduces cravings, relapses

Back 80

acamprosate

Front 81

which is more effective- acamprosate or naltrexone?

Back 81

acamprosate