1 Alcohol Flashcards
What is the most widely used psychoactive drug in the US?
Alcohol!
75% of the adult population uses it
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
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
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
Where does absorption of alcohol occur?
The stomach and small intestine
Peak blood alcohol content (BAC) occurs within _________ after the last drink and will vary between individuals
30-90 min
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)
Alcohol may acutely completely for metabolism and inhibit the breakdown of what drugs?
Benzos
Barbiturates
TCAs
Alcohol metabolism follows ______ kinetics
Zero order
Rate is INDEPENDENT of concentration
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
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
What leads to increased acetaminophen toxicity in chronic alcoholics?
Induction of the CYP2E1 metabolic pathway
What genetic things can affect how your body metabolizes alcohol?
Aldehyde dehydrogenase deficiency (—> Asian flush)
Women have lower levels of ADH than men
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
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
Cross tolerance develops between alcohol and…
Benzos
Barbiturates
Alcohol is a CNS _________
Depressant
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
Long-term chronic use of alcohol will ______ GABA receptors
Down-regulate
Long-term chronic use of alcohol causes ______ of NMDA receptors but also inhibits the effect of _______ on them
Up-regulates
Glutamate
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
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
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
