1 Alcohol Flashcards by Hannah Frank

What is the most widely used psychoactive drug in the US?

Alcohol!

75% of the adult population uses it

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What is the DSM-V definition of alcohol abuse?

Social life of an individual is impaired for at least 1 month as a result of alcohol

14 million Americans meet criteria for alcoholism/abuse

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What is the DSM-V definition of alcoholism?

The occurence of tolerance and dependence as a result of prolonged alcohol abuse

Continuous or periodic lack of control over drinking, preoccupation with alcohol, use of alcohol despite adverse consequences, and distortions in thinking, esp denial

7 million Americans are considered active alcoholics

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What is the connection between genetics and alcoholism

Incidence of alcoholism is 4x higher in offspring of alcoholics

Twice as high in identical twins compared to fraternal twins

Marked increase in release of ß-endorphins in the dopamine reward pathway —> predisposition to addiction

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Where does absorption of alcohol occur?

The stomach and small intestine

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Peak blood alcohol content (BAC) occurs within _________ after the last drink and will vary between individuals

30-90 min

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Alcohol is evenly distributed throughout the body and easily crosses both the _______ and _______

Blood-brain barrier

Placenta (fetal BAC reaches same levels as the mother’s)

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Alcohol may acutely completely for metabolism and inhibit the breakdown of what drugs?

Benzos

Barbiturates

TCAs

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Alcohol metabolism follows ______ kinetics

Zero order

Rate is INDEPENDENT of concentration

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How is alcohol metabolized?

By alcohol dehydrogenase (ADH) to acetaldehyde

Acetaldehyde is oxidized by aldehyde dehydrogenase to acetate (requires NAD+)

When NAD+ becomes less available, Lactate and acetyl-CoA accumulate

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In chronic alcoholics, what metabolic pathway is used to metabolize alcohol?

Microsomal-ethanol oxidizing system (MEOS) and CYP2E1

Chronic consumption induces both of these pathways rather than the primary ADH pathway

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What leads to increased acetaminophen toxicity in chronic alcoholics?

Induction of the CYP2E1 metabolic pathway

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What genetic things can affect how your body metabolizes alcohol?

Aldehyde dehydrogenase deficiency (—> Asian flush)

Women have lower levels of ADH than men

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How does the mechanism of action differ between Disulfiram (Antabuse) and Fomepizole (Antizol)?

Disulfiram inhibits aldehyde dehydrogenase (leads to build up of acetaldehyde and a wicked hangover)

Fomepizole (used in methanol poisoning) inhibits alcohol dehydrogenase

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What is the difference between pharmacokinetic and pharmacodynamic alcohol tolerance?

Pharmacokinetic - what your body does to the drug
• Ethanol induces CYP2E1 —> chronic uses tend to have increased ethanol metabolism

Pharmacodynamic - what the drugs do to your body
• Down-regulation of GABA receptors
• Up-regulation of NMDA receptors
• Withdrawal

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Cross tolerance develops between alcohol and…

Benzos

Barbiturates

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Alcohol is a CNS _________

Depressant

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What are the two main mechanisms of action for alcohol

Binds to GABA-a receptor to increase Cl- influx —> enhanced inhibitory GABA transmission

Increases DA in mesolimbic pathway

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Long-term chronic use of alcohol will ______ GABA receptors

Down-regulate

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Long-term chronic use of alcohol causes ______ of NMDA receptors but also inhibits the effect of _______ on them

Up-regulates

Glutamate

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Why is it so dangerous to take benzos and barbiturates together with alcohol?

They bind non-competitively to different sites on the GABA receptor —> synergistic inhibition

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What are the effects of alcohol on the CNS?

Low concentrations —> disinhibition, decreased anxiety, mild euphoria, confidence increases, memory/concentration affected, mood swings

Increased dose —> motor function and judgement are impaired, speech slurs, and ataxia may occur

CNS depressant and sedative properties become apparent

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Anterograde amnesia occurs as a result of…

Blockade of NMDA receptors

What are the effects of alcohol on smooth muscle?

Vasodilator due to acetaldehyde metabolite —> hypothermia

Can also relax the uterus (used in the past to prevent premature labor)

Effects of alcohol on the heart

Depression of myocardial contractility

Effects of alcohol on the kidney

Decreases ADH —> diuresis

SSx of acute alcohol toxicity

Emesis, stupor, coma, respiratory depression, and death Metabolic and electrolyte disturbances Hypothermia (from cutaneous vasodilation) BP and CO decreased

How do you treat acute alcohol toxicity?

Management of respiratory depression**** Prevent emesis Rehydrate

Why do we get hangovers after too much alcohol?

Buildup of acetaldehyde Dehydration Beginning of withdrawal

If seizures occur with acute alcohol toxicity, how do you treat?

Lorazepam (Ativan) - benzo Phenytoin (Dilantin) - anticonvulsant

Effects of alcohol on liver and GI tract

Gastritis and pancreatitis Liver disease is the most common medical complication**** Metabolism of alcohol lowers glutathione —> oxidative stress and tissue damage Fatty liver —> fibrosis —> cirrhosis Alcoholic hepatitis Liver cancer

When is liver cancer most likely to occur for alcoholics?

About 10 years after you stop consuming alcohol - because the liver is attempting to heal itself

Most common deficiencies for alcoholics

Folate and THIAMINE

CNS effects of chronic alcohol abuse

Wernicke-Korsakoff syndrome due to thiamine deficiency Korsakoff’s psychosis (chronic disabling memory loss) Peripheral neuropathy

What is Wernicke-Korsakoff syndrome?

Paralysis of eye muscles Ataxia Confusion Coma Death Due to thiamine deficiency

CV effects of chronic alcohol abuse

Cardiomyopathy due to direct toxic effects of acetaldehyde Arrhythmias - binges can lead to atrial and ventricular Hypertension Increased risk of stroke, CHD

Chronic alcohol abuse increases the carcinogenicity of ...

Tobacco

Effect of chronic alcohol abuse on sexual function

Testicular atrophy Impotence Gynecomastia

Effects of chronic alcohol abuse on immune system

Increased respiratory infections

Effects of chronic alcohol abuse on skeletal muscle

Atrophy

What is fetal alcohol syndrome?

Alcohol crosses the placenta —> teratogenic Microcephaly, mental retardation, poor coordination, flattened face, joint abnormalities, heart defects, and impaired immune system

Chronic alcohol use may ______ metabolism of phenytoin and oral hypoglycemics

Increase

Acute use of alcohol may inhibit the breakdown of what drugs?

Benzos Barbiturates Phenothiazines TCAs

What is the most effective way to treat alcoholism?

A combination of pharmacological and psychosocial treatments Drugs + AA

What are the four drugs used to treat alcohol addiction?

Naltrexone (ReVia) Acamprosate (Campari EC) Disulfiram (Antabuse) Topiramate (Topamax)

MOA for Naltrexone (ReVia)

Opioid receptor antagonist - blocks the ability of alcohol to stimulate the reward pathway Reduces cravings and decreases the rate of relapse by 50%

What is the most important caution to keep in mind with Natrexone?

Large doses may cause liver damage - do not use in patients with liver failure

MOA for Acamprosate (Campral EC)

Structural analogue of GABA Restores the normal balance of GABA and glutamate —> decreases craving and likelihood of relapse Excreted by the kidneys so NO liver toxicity

MOA for Disulfiram (Antabuse)

Inhibits aldehyde dehydrogenase —> acetaldehyde build up (so really really bad hangover) Long duration of action Effects can be severe - vomiting, sweating, CP, hypotension, vertigo, blurred vision, shock Dangerous and NOT recommended

What is the MOA for Topiramate (Topamax)?

Anticonvulsant drug that decreases cravings and increases abstinence in recovering alcoholics We don’t really understand the MOA though 🤷‍♀️🤷‍♀️🤷‍♀️

Alcohol withdrawal can begin within ______ and last ______

6-8 hours 7-10 days

What are the SSx of alcohol withdrawal?

Mild —> anxiety, irritability, insomnia, nausea, tachycardia Severe —> hallucinations, delirium and tremors (DTs), seizures, arrhythmias, hypotension

How to treat alcohol withdrawal

Restore electrolyte imbalances (hydration) Maybe thiamine To prevent seizures —> Diazepam (Valium) or Chlordiazepoxide (Librium) To treat seizures that are already occurring —> Lorazepam (Ativan)

SSx of methanol poisoning

Symptoms include visual disturbances “like being in a snowstorm” Formaldehyde may be smelled on the breathe (b/c it’s metabolized by ADH to toxic aldehydes and oxalates) Transient CNS excitation followed by depression, then severe metabolic acidosis Bradycardia, coma, seizures, followed by cessation of respiration

Treatment for methanol poisoning

Support respiration, lavage, alkalization for acidosis, dialysis FOMEPIZOLE (Antizol) - an alcohol dehydrogenase inhibitor to prevent production of toxic metabolites May also use ethanol if no Fomepizole