Neurology 342 - CNS Depressants: Alcohol

ethanol

Which type of alcohol is the form used in beverages?

isopropyl and methyl alcohol

Which types of alcohol are toxic?

- formic acid

- formaldehyde

What are the metabolites for methanol(methyl alcohol)

acetone

What are the metabolites for isopropyl alcohol(rubbing alcohol)?

alcohol by volume(percentage)

What does ABV stand for?

- 5oz glass of wine

- 12oz can of beer

- 12oz wine cooler

- 1.5oz of spirits

What are examples of standard drinks?

blood alcohol concentration

What does BAC stand for?

enzymes in stomach wall(ADH)

IN men, what breaks down alcohol?

passive diffusion

What type of movement does alcohol have?

Food

______ in the stomach slows absorption?

- lower total body water content

- reduced first pass metabolism

Why do women have easier time to get intoxicated over men?

alcohol dehydrogenase

What enzyme is more active in men than women?

cause fetal alcohol syndrome

As alcohol can cross the placental barrier easily, what does alcohol exposure do to the fetus?

- intellectual disability

- low birthweight

- neurological problems

- physical abnormalities

What are the symptoms of fetal alcohol syndrome?

converts ethanol to acetaldehyde(toxic)

What is the function of alcohol dehydrogenase(ADH)?

aldehyde dehydrogenase

What does ALDH stand for?

convert acetaldehyde into acetic acid

What does ALDH do?

microsomal ethanol oxidizing system

In excessive(high) doses of alcohol what is activated?

enhance activity of ADH

Some individuals have a genetic polymorphism in the ADH gene, what does this do to ADH?

- east asian

- jewish

- African american

What population is the genetic polymorphism in the ADH gene seen in?

ALDH

~30% of asian individuals also have genes that code for the inactive form of what enzyme?

rapid breakdown of ethanol and poor ALDH function = toxic build up of acetaldehyde

What is the result of these genes on alcohol?

CYP450

When the microsomal ethanol oxidizing system(MEOS) is activated what enzyme is used to convert ethanol into acetaldehyde?

damage the liver

when alcohol is combined with Tylenol or ibuprofen what does this do?

- BDZs

- barbiturates

- opiates

What drugs cause the cumulative effects to be greater when combined with alcohol?

- antibiotics

- anticoagulants

- MAOIs

Alcohol decreases the effect of what dugs?

increases CYP450 enzymes that metabolize alcohol

What is induction of regular alcohol consumption?

liver

prolonged heavy use of alcohol damages which organ?

through zero order kinetics

How is alcohol broken down and removed from the body?

~0.015%

What percentage of alcohol is eliminated per hour?

first order kinetics

Which order of kinetics does MEOS use?

alter cell membrane fluidization

- disturb BBB proteins and lipids

What does alcohol do to membrane fluidity?

NMDA receptor antagonist

What are the effects of glutamate from alcohol?

GABA A

- postive allosteric modulator

alcohol enhances which neurotransmitter receptor?

- reduce anxiety

- increase motor impairment

- increase sedation

What effects does enhancement of GABA receptors do?

- cerebral cortex

- hippocampus

- thalamus

Which brain regions are affected by GABA?

reinforce

Do opioids(endorphins) reinforce or block the effects of alcohol?

endogenous plasma endorphin levels

acute alcohol increase ____?

reduce natural endorphin levels

What does chronic administration of alcohol do to endorphin levels?

increase DA in nucleus accumbens

- reinforces alcohol use

Via endorphins what does alcohol indirectly do to dopamine?

reduce firing rate of mesolimbic neurons

- decreased DA release in nucleus accumbens

What does withdrawal after chronic use of alcohol do to DA and the mesolimbic system?

- inhibit vasopressin: ↑ urine output

- impairs memory

- hang over

- disrupt REM sleep

What are the acute alcohol use physiological symptoms?

when BAC drops a lot or is near 0

When does a hangover begin?

- acute tolerance

- metabolic tolerance

- pharmacodynamic tolerance

- behavioral and cross tolerance

IN chronic tolerance of alcohol, effects of alcohol are reduced -> what types of tolerance are affected?

occur within single exposure to alcohol

How does acute tolerance occur?

increase CYP450 enzymes(induction)

- only in heavy drinkers

How does alcohol affect metabolic tolerance?

- increase in NMDA receptors

- decrease in GABA A receptors

What are the pharmacodynamic changes in tolerance from alcohol?

sedative hypnotic

- BDZs and barbiturates

Alcohol has cross tolerance with what types of drugs?

- cardiovascular disease

- liver disease

- liver cirrhosis

List some dangers of heavy alcohol use?

- swelling in legs and abdomen

- hepatic encephalopathy

- jaundice

What are the effects of liver cirrhosis?

confusion --> progress to a coma

Over time what can hepatic encephalopathy do?

Thiamine(Vitamin B1) deficiency

What Vitamin B deficiency is a chronic effect seen in alcoholism?

- confusion

- ophthalmoplegia

- ataxia

What are the characteristics of wernicke encephalopathy?

hippocampus, mammillary bodies, frontal cortex

Which brain structures are damaged due to Korsakoff's syndrome?

- agitation

- increased HR and BP

- nausea and vomiting

- seizures

What are general symptoms of alcohol withdrawal?

anxiety, insomnia, abdominal pain

What does one with alcohol withdrawal syndrome experience from 8-10 hours after withdrawal?

high BP and increased body temp

What does one with alcohol withdrawal syndrome experience from 1-3 days after withdrawal?

seizures and delirium treatments

What does one with alcohol withdrawal syndrome experience from 1 week after withdrawal?

occur 2-5 day after drinking

- shaking, confusion, seizures, and hallucinations

What are delirium treatments?

~15%

What percent of people with severe delirium treatments die from alcohol withdrawal?

seizure activity

Due to the pharmacodynamic tolerance, what does the increase glutamate and reduced GABA during withdrawal lead to?

excessive influx of Ca2+

What does elevated glutamate cause?

use of BDZ drugs

- prevent alcohol withdrawal symptoms

How do people detox when facing alcohol withdrawal syndrome?

increased tendency for seizure during alcohol withdrawal due to increase of glutamate and decrease of GABA

Why does Kindling refer to?

alcohol use disorder

What does AUD stand for?

increase brain and endocrine stress system activity

Since alcohol is used to relieve stress and is reinforced during stressful period, alcohol also increase what kind of activity?

additional stressor

- lead to increased alcohol use

alcohol itself = ?

- disulfiram

- naltrexone

What are two strategies are used to treat AUD to make drinking unpleasant?

inhibit ALDh

What does disulfiram do?

opioid receptor antagonist

- block effect of alcohol induced endorphin release

What does naltrexone do?