Komiskey 2-5-08 Alcohol And Pharm

Front 1

know the incidence and health effects of alcohol use.
know the pharmacokinetics and pharmacodynamics of acute and chronic alcohol use.
know the symptoms of tolerance and addiction to alcohol
know the drugs used to treat alcoholism.
know the mechanism of action of drugs used to treat alcoholism.
know the effectiveness and side effects of drugs used to treat alcoholism.

Back 1

obj

Front 2

HOW MANY million Americans (8.5% of the population age 18 and older) suffer from alcohol use disorders (AUDs*)

Back 2

18 million

Front 3

Over HOW MANY million of our young (18% of the population age 12-17) report drinking monthly with more than half engaging in high-risk drinking patterns

Back 3

4 million

Front 4

Alcohol is 3rd mc cause of death in the US (2000) behind what

Back 4

tobacco and poor diet/phys activity

Front 5

Alcohol is the 3rd biggest risk factor for disease in developed countries behind what

Back 5

tobacco and BP

Front 6

% of US pop that drink alcohol

Back 6

65

Front 7

gender distribution responsible for drinking all the alcohol

Back 7

74% - males
26% - females

Front 8

73% of the alcohol is consumed by what percent of the population

Back 8

10%

Front 9

The most harmful pattern of drinking

Back 9

binge drinking: 5 drinks for men, 4 for women, in 2 hours

Front 10

"Moderate Drinking" suggestions for men and women

Back 10

up to 2 drinks/day for men; up to 1 drink/day for women

Front 11

Nearly 3 in 10 U.S. adults engage in WHAT high-risk drinking patterns1

Back 11

Men: more than 14 drinks in a typical week
more than 4 drinks on any day
Women: more than 7 drinks in a typical week
more than 3 drinks on any day

Front 12

"Key" age in brain development (highlighted in the talk)

Back 12

around 16

Front 13

The ______ system governing emotions matures earlier than the frontal cortex, responsible for planning, self-control, and decision-making.

Back 13

limbic

Front 14

What type of person is more likely to develop alcoholism:
Individuals with a

low level
High level

of response to alcohol

Back 14

low level

Front 15

Age group with highest prevalence of alcohol dependence
2001-2002

Back 15

18-20

Front 16

Which are adolescents more sensitive to (compared to adults):

sedation, hangover, ataxia

social facilitation

disruption of spatial memory

Back 16

social facilitation

disruption of spatial memory

Front 17

Under stress, adolescent monkeys DO WHAT to their alcohol intake

Back 17

double their alcohol intake

Front 18

Pharmacokinetics: What parameters are we talking about

Back 18

Absorption
Distribution
Metabolism

Front 19

Pharmacodynamics: What parameters are we talking about

Back 19

CNS effects
Tolerance
Alcohol as a reinforcer
Neuropharmacological effects

Front 20

alcohol is primarily absorbed in the GI where?

Back 20

duodenum

Front 21

Peak blood alcohol concentration (BAC) depends on:
Amount and alcohol concentration of beverage
Rate of drinking
____ consumption and composition
Gastric emptying and gastric metabolism
Hepatic _____ pass

Back 21

Peak blood alcohol concentration (BAC) depends on:
Amount and alcohol concentration of beverage
Rate of drinking
Food consumption and composition
Gastric emptying and gastric metabolism
Hepatic first pass

Front 22

Succinct description of alcohol "kinetics"

Back 22

Zero order kinetics

Front 23

Alcohol Molecules not ionizable; hence digestive system __ and blood __ have no effect on absorption.

Back 23

Alcohol Molecules not ionizable; hence digestive system pH and blood pH have no effect on absorption.

Front 24

BAL units?

Back 24

(mg/100ml of blood):

Front 25

Regardless of how much or how little you drink alcohol will metabolize at a _____ rate

Back 25

constant

Front 26

Accumulation of WHAT CHEMICAL associated with headache, gastritis, nausea, dizziness (hangover)

Back 26

acetaldehyde

Front 27

Aldehyde dehydrogenase inhibition: what famous drug?

Back 27

(disulfiram)

Front 28

Polymorphism for alcohol dehydrogenase occurs at what "ADH" gene loci

Back 28

ADH2 and ADH3 loci

Front 29

15% of Black Americans have ADH2*3 allele which does what to their alcohol metabolism

Back 29

increased alcohol metabolic rate

Front 30

50% of Asians have ALDH2*2 allele . This des what to their alcohol metabolism

Back 30

--> decreased elimination of acetaldehyde (and alcohol)
--> flushing response

Front 31

rate-limiting step; slowest step in alcohol metabolism.

Back 31

Alcohol dehydrogenase

Front 32

For the majority, the accepted excretion rate is between WHAT (mg/100ml/hr)

Back 32

10 and 20mg/100ml/hr, with a mean of 15.

Front 33

What "system" also metabolizes alcohol; handles about 5 to 10% at low blood levels

Back 33

The Microsomal Ethanol-Oxidizing System (MEOS)

Front 34

___ is also responsible for metabolism of other drugs like the barbiturates.

Back 34

MEOS

Front 35

Metabolized at rate of 1.5 oz of 80 proof p/hour or _ beer p/hour

Back 35

1

Front 36

1 drink per/50lbs per hour to get BAC of WHAT

Back 36

0.08

Front 37

How much can you drink per/hour before you kill yourself?

Back 37

BAC @ .4 – LD50-death in 50% of population
Alcohol poisoning-DEATH @ approximately 5X the legal limit
Takes less if you don’t drink, are taking other meds and/or have other medical conditions

Front 38

Another useful(?) Stereotype:

Many _____(race) lack sufficient acetaldehyde dehydrogenase activity to fully metabolize alcohol & begin vomiting more easily

Back 38

Asians

Front 39

Stereotype:

Many ______(race) have increased acetaldehyde dehydrogenase & don’t get sick as easily

Back 39

Indians

Front 40

How do you increase alcohol metabolic enzyme activity

Back 40

Acute high doses-binges of alcohol increase enzyme activity

Front 41

How do you decrease alcohol metabolic enzyme activity

Back 41

Chronic alcohol decreases enzyme activity-less enzyme more alcohol in system longer

Front 42

Alcohol is a CNS depressant
Apparent stimulatory effects result from depression of _______ control mechanisms in the brain

Back 42

inhibitory

Front 43

Feel more of alcohol’s behavioral effects before BAC levels reach peak concentration

This means WHAT (relates to drunk driving)

Back 43

that we begin to feel less drunk before the alcohol has been metabolized

Front 44

What is BAC if you have the following alcohol effects:

Impaired balance, speech, vision, hearing, muscle coordination. Euphoria.

Back 44

0.08-0.09

Front 45

What is BAC if you experience the following effects:

Sleepiness Gross impairment of physical and mental control.

Back 45

0.14-0.15

Front 46

Ethanol has its most pronounced actions on ion channels, particularly inhibiting the _____ excitatory neurotransmitter receptor

Back 46

glutamate-NMDA

Front 47

Ethanol potentiates the _____-inhibitory neurotransmitter receptor

Back 47

GABA-A

Front 48

____ Ethanol Consumption Reduces GABA-mediated Inhibition and Abolishes Ethanol Potentiation

Back 48

Chronic

Front 49

Ethanol enhances WHAT (neurotransmitter) release in the “pharmacological reward” pathway

Back 49

dopamine

Front 50

Ethanol has direct excitatory actions on dopamine containing neurons in the ______ _____ area of the brain

Back 50

VTA

Front 51

Ethanol appears to release dopamine from the VTA and nucleus ______ via interactions with multiple neurotransmitter receptors

Back 51

NAC = nucleus accumbens

Front 52

What is ethanol's effect of Adenosine transporter

Back 52

Ethanol inhibits adenosine transport through a specific subtype of adenosine transporter

Front 53

Norepinephrine transporter - _________ by ethanol

Dopamine transporter – ___________ by ethanol

Serotonin transporter - ___________ by ethanol

Back 53

Norepinephrine transporter - inhibited by ethanol

Dopamine transporter – facilitated by ethanol

Serotonin transporter - facilitated by ethanol

Front 54

WHAT has been proposed as an alcohol antagonist was found to have undesirable side effects such as its ability to induce convulsions.

Back 54

RO 15-4513,

Front 55

When drinking is discontinued after 5 nights, there is REM ______ on the 6th night

Back 55

rebound

Front 56

When alcoholics stop drinking, majority, about 90%, of their sleep time is spent in ___; other sleep disturbances may last as long as long as 200 weeks, about 4 years

Back 56

REM

Front 57

70 mg/100ml BAL decreases visual acuity by lowering the ___

Back 57

CFF

Front 58

Romberg sway test: WHAT BAL can cause a 40% decrease in steadiness as measured by the amount of swaying.

Back 58

60mg/100ml

Front 59

Grayout is more common; cannot remember events that happened while drunk but can be recalled when drunk again or if reminded; this is likely a result of _________

Back 59

dissociation

Front 60

Alcohol’s effect on driving performance is observable at about WHAT BAL.

Back 60

50 to 80 mg/100 ml

Front 61

fMRI studies revealed that alcohol weakens the connection between the frontal lobes and the _______, the motor areas of the brain, which may partly explain disinhibition.

Back 61

striatum

Front 62

Useful for Vegas gambling:

The stimulus properties of alcohol can be blocked by ____ receptor blockers, but not by haloperidol, a DA D2 blocker.

Back 62

5-HT3


(I thought 5-HT3 was in the stomach, not the brain)

Front 63

Maximum tolerance develops in ____ weeks in humans requiring doses to be increased from 30 to 50% to overcome it.

Back 63

a few

Front 64

Positive reinforcing effects:

Back 64

Gain pleasure
Altered consciousness
Conform to behavior of peers

Front 65

Negative reinforcing effects:

Back 65

Relief of stress and negative emotions
Relief of withdrawal symptoms

Front 66

Drug for alcohol coma

Back 66

thiamine

Front 67

-extreme memory deficits for past events,
-inability to remember new material,
-disorientation and confusion
-associated with damage in certain parts of the cerebral cortex first noted by Wernicke -called Wernicke’s disease

Back 67

Korsakoff’s psychosis

Front 68

2 stages of withdrawal

Back 68

Stage 1: Early minor syndrome.
Stage 2: Late major syndrome

Front 69

Stage 2: Late major syndrome
AKA

Back 69

delirium tremens, DTs; increasing agitation, disorientation, confusion, and hallucinations; seizures may also occur

Front 70

How long does stage 1 last?

Back 70

Starts about 8 to 12 hrs post-drinking bout, and over within 48 hrs.

Front 71

how long does stage 2 last

Back 71

These symptoms may last as long as 7 to 10 days, and can cause death if left untreated.

Front 72

What is the time period for having withdrawal seizures during withdrawal?

Back 72

in the first 2 days

Front 73

Drugs to help get off alcohol

Back 73

Disulfiram
Naltrexone -
Acamprosate - NMDA blocker
Benzodiazepines - can stop seizures
SSRIs

Front 74

Acamprosate inhibits ____ influx through NMDA glutamate receptors

Back 74

calcium

Front 75

Acamprosate increases synaptic availability of the inhibitory neurotransmitter _____

Back 75

taurine

Front 76

Acamprosate acts as a partial co-agonist at the ______ receptor through an allosteric interaction

Back 76

glutamate

Front 77

A once-a-month injectable drug that cuts cravings for alcohol is now available
Vivatrol, an extended release form of _____

Back 77

naltrexone

Front 78

Medications for Treating Alcohol Dependence – Under Investigation

Back 78

Topiramate
Valproate
Ondansetron
Nalmefene
Baclofen
Antalarmin
Rimonabant