Pharm Winter 3 Etoh

Front 1

how is EtOH similiar to other CNS depressants

why can overdose happen if depressants are combined

Back 1

depress synaptic transmission via GABA a R (same as barbituates, benzo)

Front 2

what are the major enzymes involved in EtOH metabolism

Back 2

1. Alcohol Dehydrogenase: EtOH --> acetaldehyde. Blocked by fomepizole


2. Aldehyde Dehydrogenase: Acetaldehyde --> acetate. Blocked by disulfiram

Front 3

How does disulfiram work

Back 3

blocks Aldehyde dehydrogenase

Front 4

what is the kinetics of EtOH metabolism, how can this realate to overdose

Back 4

zero order!

**there is a STEEP dose response curve. (Overdose is easy)

**elimination is dependent only on time so you have have really high levels

Front 5

Alcohol Abuse

Alcoholic

Back 5

abuse: cant limit comsumption. social life is impaired for at least one month bc of EtOH

ism: drink despite adverse effects. tolerance (dynamic/kinetic) has developed

Front 6

what will long term EtOH use do to GABA r

what about NMDA

*what happens with withdrawal

Back 6

it stim the GABA R (so in the presence of an antagonist a R will DOWN regulate. we no longer have inhibitory signaling going on)

Upregulates NMDA:

**when we withdawal we have LOTS of NMDA nad little GABA

Front 7

how does EtOH affect the NMDA receptor

Back 7

inhibits NMDA- excitatory glutamate on this R which is involved in learning and memory, and seizure. this is associated with amnesia with drinking

**these will upregulate with chronic use

Front 8

ok so you say EtOH is a depressant, why then do ppl seem so happy when they are drunk?!

Back 8

**low dose will inhibit the inhibitory pathways --> disinhibition, this makes us smart, funny, and pretty

**at higher dose: begins to inhibit the excitatory paths also and we get the CNS depression

Front 9

what controls the smnesia associated with EtOH

Back 9

NMDA receptor inhibition (learning, memory, seizures. keep in mind this upregulates when EtOh is used chronically)

Front 10

what happens with low dose of EtOH

what happens with higher dose

Back 10

LOW
1. inhibits inhibitory paths --> disinhibition
2. impairment of intellectual/motor fx. dont drink and drive!
3. decrease anxiety/sedation, mild euphoria

HIGHER:
1. motor fx, judgement, speech, ataxia. INTOXICATION

Front 11

what happens to sleep in chronic EtOH use

Back 11

you get fragmented sleep with decreased REM

Front 12

how is EtOH abs, how does this differ in men and women

Back 12

abs in stomach/sm intestine via alcohol dehydrogenase

**increased abs with no food
**men have more alcohil dehydrogenase so will metabolize faster (women get more drunk with same amt of booze bc they have less enzyme for metabolism)

Front 13

gastric metabolism of alcohol is much ____ in women than men

Back 13

lower

**women dont have as much alcohol dehydrogenase

Front 14

does EtOH cross BBB? placenta?

Back 14

yes to both

Front 15

what is required for EtOH metabolism

Back 15

NAD+

*both Alcohol dehydrogenase and aldehyde dehydrogenase require it

**zero order elimination (dependent only on time for elimination)

**when there is LOTS of EtOH we cant have NAD available for the TCA so we favor faftty acid synthesis

Front 16

fomepizol
disulfurim

*what enzyme do they work on, what is the use

Back 16

Femepizol: inhibits alcohol dehydrogenase. used to treat posioning

Disulfurim: inhibits aldehhyde dehydrogenase. used to prevent ppl from drinking bc of the ill effects of acealdehyde build up. but its dangerous and dosent work well

Front 17

what is a beer gut biocehmically speaking

Back 17

etoh metabolism required so much NAD+ that lactate increases and shuts down the TCA cycle, this makes us switch to fatty acid synthesis bc there is lots of acetyl CoA

Front 18

what is pharmakokinetic tolerance to EtOH
what is pharmacodynamic tolerance

Back 18

KINETIC: induce your own enzymes (CYP) so you metabolize faster. Lower BAC (blood alcohol content) for same amt drank , his is why ppl can out drink you

DYNAMIC tolerance: upregulation of GABA and down regulation of NMDA (tolerant to the effects of EtOH)

Front 19

why do EtOH get liver damage

Back 19

NAD used so we dont restore glutathione, we get oxidative damage in the liver

Front 20

when might acetaldehyde build up

Back 20

acetaldehyde is the product of alcohol dehydrogenase

1. seen in asians who are aldehyde dehydrogenase deficit

2. Disulfiram- inhibits

**anyway, acetaldehyde build up is assoicate with hang over, it makes you red, it flushed you, HA, nausea

Front 21

should you take acetemenophen (tylenol) with EtOH

Back 21

NO WAY!!!!

EtOH will indice enzymes so tylenol is metabolised faster and its toxic metabolite builds up and exceeds the capacity that the liver can handle

**theraputic amts of acetemenophin can cause hepatoxicity in alcoholisc bc enzymes are indiced

Front 22

what happens to effects of other drugs with CHRONIC nad ACUTE EtOH use

Back 22

CHRONIC EtOH:
increase metabolism of drugs bc EtOH indiced P450 system

Acute:
EtOH will bind up sited in hte P450 system so drugs are metabolized SLOW

Front 23

what drugs are at increased risk of toxicity when used with ACUTE EtOH consumption

Back 23

barbituates
benzo
TCA

**acute EtOH competes for metabolism so the effects of the drugs last longer

Benzo and barbituates and EtOH all stim GABA

Front 24

what type of tolerance

1. drinking lots induces the enzymes for EtOH metabolism so you have increased metabolism

2. chronic drinking will upregulate GABA and down regulate NMDA R

Back 24

1. pharmacokinetic tolerance

2. pharmacodynamic tolerance

Front 25

what does EtOH do to Smooth MM

Back 25

1. Cutaneous dilation: can lead to hypothermia (drinking wont make you warm it just brings blood to skin

2. Relaxes Uterus: used IV to prevent premature labor

Front 26

what does EtOH do to Kidney

Back 26

decreases ADH so acts as a DIURETIC

Front 27

what is EtOH toxicity?
tx?

Back 27

1. emesis, stupor, coma, respiratory depression, possible death

2. treat by managing airway and prevent aspiration of vomitous

3. thiamine to prevent neuro damage

4. dehydration/electrolyte imbalance

5. seizure- tx with phenytoin

6. hypothermia- cutaneous dilation

Front 28

what does chronic EtOH do to nutrition

Back 28

malnourished, esp thiamine and folate

**give thiamine to prevent neuro damage

Front 29

what does chronic EtOH do to stoomach and pancrease

Back 29

Pancreas- damages cells, pancreatitis (recurrent episodes)

Stomach- makes lots of acid --> errosive gastritis, malabsorption, reflux and ulcers in esophagous or duadonem

Front 30

what does chronic EtOH do to the liver

Back 30

EtOH decreases glutathione so we get oxidative damage from free radicles

Acetealdehyde does lipid peroxidation to cause fatty liver --> fibrosis (necrosis/inflammation) --> cirrhosis (collagen deposition)

**liver cancer 10 years after EtOH is stopped, liver tries to heal

Front 31

what happens with elevated acetaldehyde levels in the liver

Back 31

Alsochol is converted to acetaldehydy by alcohol dehydrogenase

*the acetaldehyde will increase lipid peroxidation leading to fatty liver

**can get fatty liver in just a few days after drinking --> fibrosis --> cirrhosis

Front 32

tell me about hepatitis and EtOH

Back 32

increased incidence of viral hepatitis
can get EtOH hepatitis also

Front 33

tell em about cancer risk in the liver of EtOhics

Back 33

increased risk

*usually happens like 10 years after they stop drinking- liver tries healing itself

Front 34

what happens to the heart with chronic EtOH

Back 34

small amts cardio protective (increase HDL)

Lots- arrhythemia, decrease contractility, cardiomyopathy, HTN, stroke

Front 35

what happens when there is increased acealdehyde in the heart

Back 35

cardiomyopathy

**more common in women, if you stop drinking this usualyl goes away

Front 36

what does chronic EtOH do to
HTN
stroke
cardiomyopathy

Back 36

increased risk for all!

**also have liver damage bc of decreased glutathione

Front 37

what is the effect of EtOH on preggo!

Back 37

EtOH crosses placenta

FAS- congenital malformation and mental retardation

DONT DRINK WHEN PREGGO

Front 38

ok so we know that when ppl use EtOh chronically they increase risk of liver cancer, what about its carcinogenicity in general

Back 38

increased carcinogenicity, exp when ppl smoke!!!!!

alimentary system, respiraroty system, breast

Front 39

what are some less known effects of EtOH

Back 39

1. decerased REM
2. anemia (folic acid deficit)
3. decreased testosterone (small balls, impotence, gynomastia)
4. decrease immune system
5. sk mm atrophy
6. neuropathy (optic N damage)
7. hypothermia (cutaneous dilation)

Front 40

what is wernicke korsakoffs

Back 40

Wernicke encephalopathy- parapysis of eye mm, ataxia, confusion

Korsakoff- memory loss

**thiamine deficit

Front 41

tolerance the effects of EtOH is what

tolerance bc of increased metabolism is what

Back 41

pharmacodynamic (this is what gives withdrawal)

pharmacokinetic

GABA is upregulated, NMDA is down regulated

Front 42

what type of tolerance leads to withdrawal

Back 42

pharmacodynamic

**GABA upregulated, NMDA downregulated

Front 43

is there cross tolerance to barbituates, and benzo when you develop pharmacodynamic tolerance to EtOH

Back 43

yep

Front 44

does lethal dose change as you develop pharmacodynamic and pharmacokinetic tolerance to EtOH

Back 44

nope!!! super steep gradient btwn dose response curve to lethal dose

Front 45

is alcoholism genetic

Back 45

ya

*ppl who are genetically likely to be alcoholic will increased release of endorphins in the dopamine reward path when they use

Venral tegmental --> nuc accumbans --> prefrontal cortex

**in EtOHics this path is underactive then EtOH makes it go BOOM

**its a disease

Front 46

what are some signs of alcoholism, who is affected

Back 46

affects ppl from ALL walks of life!!!

malnutrition, physical degeneration, tremir, infections, decreased stamina, increased liver enzymes, recurrent pancreatitis etc

Front 47

what are the sx of EtOH withdrawal

Back 47

mild: anxiety, irritaable, insomnia, nightmare, tachycardia, palpitations

severe: anxiety, fear, hallucinations, delirium and tremors, tonic clonic seizures, arrhythemias, HTN

**CAN BE SERIOUS AND LIFE THREATENING

**GABA is down regulated, NMDA is upregulated

Front 48

what is the reason we treat EtOH withdrawal

Back 48

prevent seizure, delirium and tremor, and arrhythemias

**tx with long acting benzo (chlordiazepoxide, diazepam) or short acting if there is liver damage (oxazepam)

Front 49

what is haploperidol

Back 49

antipsychotic used to treat hallucinations when ppl whithdrawal from EtOH

Front 50

what antipsychotic is used to treat EtOH withdrawal (prevent hallucinations)

Back 50

haloperidol

Front 51

what is the general treatment schema to treat EtOH ism

Back 51

1. prevent seizure, delerium, arrhythemias in withdrawal with benzo
2. CHRONIC treatable disease with frequent relapse
3. pharmalogic
4. psychosicial** super important

Front 52

what is naltrexone

Back 52

blocks the EtOH from stim pleasure path

**its an opoid antagonist, so the b endorphin that is released when you drink is NOT able to stim the pleasure path

**decreases cravings, decreases relapse

**bad bc it can cause liver damage nad nausea

Front 53

what drug will decrease cravings by inhibiting the pleasure path that is associated with EtOH

Back 53

Naltrexone

Front 54

naltroxone is really good for the treatment of EtOHics bc it decreases cravings by blocking opoid R, this means that EtOH wont stim the pleasure path. what are some bad things

Back 54

1. nausea
2. cause liver damage
3. opoid pain killers wont work

Front 55

what is acamprosate

Back 55

gets GABA and glutamate back in balance fast after chronic EtOH messes it up

**makes ppl not want to drink as much if they are still drinking
*no abuse potential
*no liver toxicity

Front 56

what drug is good for decreasing relapse in alcoholics bc it has NO abuse potential and NO liver toxicity. how does it work

Back 56

acamprosate

**this restores the balance of GABA and glutamate

Front 57

what drug is used to restore the balance btwn GABA and glutamate

Back 57

acamprosate

**restores the balance and makes ppl not want to drink as much
*no abuse potential- no anxiolytic ot antidepressant effects
**NO liver damage, renal excretion

Front 58

what is disulfiram

Back 58

Blocks Aldehyde Dehydrogenase- lots af acetaldehyde will build up WHEN YOU DRINK EtOH, alone it has no effect (build up causes flushing, HA, nausea, confusion, sweat, comit, chest pain, Hypotension)

DANGEROUS, NOT recommended

**stays in system for a long time so avaoid ANYTHING with EtOH- mouthwash etc

Front 59

what will cause acetaldehyde to build up, what happens

Back 59

disulfiram- blocks aldehyde dehydrogenase

**when taken with EtOH you get flushing, HA, nausea, confusion, hypotension, chest pain, comit, shock...

**LONG t1/2 so avoid anything with EtOH for like 3 days!

Front 60

what drugs are simliar to disulfiram

Back 60

metronidazole
cephalosporins
oral hypoglycemic agents

**dont combine with EtOH, they can block aldehyde dehydrogenase and acetaldehyde will build up

Front 61

is disulfiram a good drug

Back 61

nope, not recommended!

**blocks aldehyde dehydrogenase, acetaldehyde build up when EtOH is used. Acts for a long time, avoid etOH in things like mouthwash

**metronnidazole, cephalosporins, and oral hypoglucemics will mimic this

Front 62

what is the role of antidepressants in alcoholics

Back 62

lots of alcoholics are depressed, when you treat them they are less likely to relapse

**not mood altering, not addictive

Front 63

what is ondansetron

Back 63

prevent relapse/decrease consumption in EARLY ONSET alcoholics

Front 64

what is topiramate

Back 64

anticonvulsant that decreases cravings and increase absitinance

Front 65

what is a great non pharmalogical treatment for alcoholics

Back 65

alcoholics anonymous

Front 66

how is methanol and ethylene glycol poisioning treated

Back 66

fomepizole- blocks alcohol dehydrogenase

Front 67

what happens when methanol is ingested? what can be used to treat it, what does it feel like for the pt

Back 67

its metabolized by alcohol dehydrogenase into formate (TOXIC)

**fomepizole can be used to INHIBIT alcohol dehydrogenase so that the toxic formate isnt made

**pt has visual disturbances, "Like being in a snowstorm"

Front 68

when might a pt state their vision is like a snowstorm

Back 68

when they have methanol poisioning

Methanol is converted by alcohol dehydrogenase to formaldehyde and then to formate

**treat with fomepizole

Front 69

what happens when ethylene glycol is ingested

how is it treated

Back 69

its metabolized by alcohol dehydrogenase into aldehydes and oxalates which are TOXIC --> METABOLIC ACIDOSIS

*give ethanol or fomepizole

Front 70

if treatment for a specific condition requires ethanol or fomepizole what may have been the problem

Back 70

1. ethylene glycol poision (antifreeze)
2. methanol poision