Alcohol used disorder Flashcards
Which receptor is activated by EtOH?
GABA receptors.
How does alcohol acutely affect NMDA and GABA receptors?
Alcohol is a GABA-A agonist (causing sedation) and an NMDA receptor antagonist (reducing excitatory transmission). This leads to CNS depression.
What are the acute features of intoxication?
- Stupor
- Overall central nervous system depression
- Slurred speech
- Ataxia
- Emotional lability
- Slowed respirations
- Coma
What is alcohol use disorder (AUD)?
A maladaptive pattern of alcohol use causing functional impairment and distress, classified by DSM-5 criteria.
What are the risk factors for alcohol use disorder?
- Family history (multifactorial genetic basis)
- Psychiatric disorders
- Early exposure to alcohol
- Social factors
How is alcohol use disorder diagnosed according to DSM-5?
At least 2 of 11 criteria within 12 months, including failed obligations, hazardous use, tolerance, withdrawal, cravings, and inability to cut back.
Why do chronic alcohol users develop tolerance?
With chronic use, NMDA receptors are upregulated (to compensate for inhibition), and GABA-A receptors are downregulated, requiring more alcohol for the same effect.
How does chronic alcohol use affect NMDA and GABA receptors?
Chronic alcohol use upregulates NMDA receptors and downregulates GABA-A receptors. This leads to withdrawal symptoms when alcohol is stopped due to excessive NMDA excitation and decreased GABA inhibition.
What happens when chronic alcohol use is suddenly stopped?
The brain is left with excess NMDA activity (excitotoxicity) and low GABA function, causing symptoms like agitation, tremors, seizures, and hallucinations.
What are the gastrointestinal complications of chronic alcohol use?
Gastritis, hepatitis, cirrhosis, pancreatitis, increased risk of esophageal and oropharyngeal cancers.
What are the cardiovascular complications of chronic alcohol use?
Dilated cardiomyopathy, hypertension, and arrhythmias like atrial fibrillation.
What are the neurological complications of chronic alcohol use?
Peripheral neuropathy, cerebellar degeneration, Wernicke-Korsakoff syndrome.
What causes Wernicke’s encephalopathy?
Thiamine deficiency, often precipitated by glucose administration without prior thiamine replacement.
What are the classic triad symptoms of Wernicke’s encephalopathy?
Nystagmus, ophthalmoplegia, ataxia, plus confusion.
What is Korsakoff syndrome?
An irreversible amnestic disorder with confabulation and apathy due to untreated Wernicke’s encephalopathy.
What is the treatment for Wernicke-Korsakoff syndrome?
IV thiamine before glucose administration.
What is the primary cause of autonomic instability in alcohol withdrawal?
Unopposed increased NMDA receptor activity leads to increased sympathetic output, causing hypertension, tachycardia, and diaphoresis.
What is the timeline of alcohol withdrawal symptoms?
6-24 hours: diaphoresis, palpitations, insomnia, tremors, anxiety, GI upset.
12-48 hours: seizures, hallucinations (visual or tactile), stable vitals.
48-96 hours: delirium tremens (DTs) indicated by agitation, hallucinations, hypertension, fever, death.
What is the mechanism of alcohol withdrawal?
Increased NMDA receptor activity and decreased GABAergic inhibition due to chronic alcohol use and sudden cessation.
Why does alcohol withdrawal cause seizures?
Chronic alcohol use suppresses NMDA receptor activity and enhances GABA-A function. When alcohol is abruptly stopped, NMDA receptors become overactive, leading to excitotoxicity and seizures.
What is the first-line treatment for alcohol withdrawal?
Benzodiazepines (e.g., lorazepam, diazepam, chlordiazepoxide) to enhance GABA-A receptor activity.
How does benzodiazepine treatment help in alcohol withdrawal?
Benzodiazepines enhance GABA-A receptor activity, counteracting the excitatory NMDA overactivity and preventing seizures and delirium tremens (DTs).
Which benzodiazepines are preferred in alcohol withdrawal?
Long-acting: diazepam, chlordiazepoxide
Short-acting for liver disease: lorazepam, oxazepam, temazepam (LOT drugs).
Which benzodiazepines is used for patients with liver failure?
lorazepam
What are the FDA-approved medications for alcohol use disorder?
Naltrexone, acamprosate, and disulfiram.
What are the key differences between acamprosate, naltrexone, and disulfiram?
Acamprosate modulates NMDA and GABA to reduce cravings and withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol’s rewarding effects. Disulfiram inhibits aldehyde dehydrogenase, causing an aversive reaction to alcohol ingestion.
Which medication can be used while the patient is still drinking?
Naltrexone can be initiated even if the patient is still drinking, as it reduces cravings and the pleasurable effects of alcohol.
How does naltrexone work in alcohol use disorder?
Opioid receptor antagonist that reduces alcohol cravings and reward effects.
When is naltrexone contraindicated?
In patients taking opioids or with acute hepatitis/liver failure.
Which medications require abstinence before starting?
Acamprosate and disulfiram should only be started after detoxification when the patient is abstinent.
How does acamprosate work in alcohol use disorder?
Acamprosate modulates glutamate neurotransmission by acting as an NMDA receptor antagonist and a positive allosteric modulator of GABA receptors, reducing withdrawal symptoms and preventing relapse. By being a glutamate (NMDA) modulator, acamprosate helps maintain abstinence by reducing withdrawal-related cravings.
When should acamprosate be initiated?
Acamprosate should be started after detoxification to help maintain long-term abstinence by stabilizing the excitatory-inhibitory balance in the brain.
What is the best medication for alcohol use disorder in a patient with liver disease?
Acamprosate, because it is renally excreted and does not affect liver function.
When should acamprosate be used over naltrexone?
In patients with liver disease or opioid use disorder (since naltrexone is contraindicated in these patients). Acamprosate is preferred in patients with liver disease because it is excreted by the kidneys and does not affect hepatic function.
What is the mechanism of disulfiram?
Inhibits aldehyde dehydrogenase, leading to acetaldehyde accumulation and severe adverse reactions if alcohol is consumed.
When is acamprosate contraindicated?
In patients with severe renal impairment (CrCl < 30 mL/min), as it is excreted unchanged by the kidneys.
What is the purpose of disulfiram in alcohol use disorder?
Used as a deterrent for alcohol use in highly motivated patients under supervision.
What are the side effects of disulfiram?
Flushing, headache, vomiting, palpitations, dyspnea if alcohol is consumed (disulfiram reaction).
Which other medications are used in alcohol use disorder?
Baclofen, topiramate, gabapentin, SSRIs, ondansetron (less commonly used).
What are validated screening tools for alcohol use disorder?
CAGE questionnaire (Cut down, Annoyed, Guilty, Eye-opener), AUDIT, MAST.
Which medication used for alcohol use disorder has potential for misuse?
Gabapentin and baclofen have potential for misuse, particularly for self-medication.
How is naltrexone sometimes misused?
Some individuals may attempt to combine naltrexone with naloxone to counteract opioid blockade, though this is uncommon.
Why is crushing and inhaling some alcohol use disorder medications a concern?
Certain formulations of baclofen or gabapentin can be abused via inhalation or IV injection, increasing overdose risk.
What is the preferred treatment for alcohol withdrawal seizures?
Benzodiazepines (first-line); phenytoin is not effective for alcohol withdrawal seizures.
What is the risk of untreated delirium tremens?
High mortality rate due to autonomic instability, seizures, and cardiac arrhythmias.
Why should thiamine be given before glucose in alcohol withdrawal patients?
To prevent Wernicke’s encephalopathy, which can be precipitated by glucose administration in thiamine-deficient patients.
How does chronic alcohol use affect NMDA and GABA receptors?
Chronic alcohol use increases NMDA receptor activity and downregulates GABA receptors, leading to withdrawal symptoms when alcohol is stopped.
