1- Alcohol Flashcards
What is the most psychoactive drug in the US?
Alcohol
How is alcohol abuse defined?
Social life impaired for at least 1 month
How is alcoholism defined?
Prolonged alcohol use leading to tolerance and dependence (also continuous or periodic lack of control over drinking, preoccupation with alcohol, use of alcohol despite adverse consequences, and distortions in thinking (especially denial))
How does genetic predisposition contribute to alcoholism?
Increased release of beta-endorphins in dopamine reward pathway
What are the MOAs of alcohol? (4)
- CNS depressant
- Binds to/ enhances inhibitory GABA transmission
- Increases dopamine in mesolimbic pathway
- Inhibits effects of glutamate on NMDA receptor
Do plasma levels of alcohol change in pharmacokinetics or pharmacodynamics?
Pharmacokinetics (pharmacodynamics = plasma levels NOT changing but body is changing)
What parts of the body is alcohol absorbed from?
Stomach and small intestine
When does BAC peak?
Within 30-90 min after last drink
What 2 things does alcohol cross?
BBB and placenta
Chronic alcohol use can lead to up and down regulation of what?
Down regulation of GABA receptors Up regulation of NMDA receptors
Chronic alcohol use is associated with cross tolerance with what 2 drug classes?
Benzodiazepines and barbiturates (due to both binding to GABA receptors)
What order kinetics does alcohol display?
Zero order (metabolism rate independent of concentration)
What metabolizes alcohol? (2)
ADH > MEOS/CY2E1
What is the metabolism pathway of alcohol? (3 steps)
Alcohol → acetaldehyde (via ADH) → acetate (via ALDH, requires NAD+)
How does an ALDH deficiency affect alcohol metabolism?
Metabolize alcohol more slowly (women have lower ALDH levels)
What is the MOA of Disulfiram?
Inhibits aldehyde dehydrogenase (ALDH)
How are MEOS/ CYP450s and CYP2E1 affected by chronic ethanol consumption?
Induced by chronic ethanol consumption (→ increased ethanol metabolism → need more alcohol to get drunk)
Alcohol + Acetaminophen can lead to what?
Liver damage
How does alcohol interact with phenytoin and oral hypoglycemic agents?
Increases metabolism
How does alcohol interact with benzodiazepines, barbiturates, phenothiazines and tricyclic antidepressants (TCAs)?
Synergistic CNS depression
What are the effects of alcohol at low levels?
Disinhibition
When does alcohol cause impaired motor function and judgement, CNS depression/ sedative effects, anterograde amnesia (blockade of NMDA receptors)?
Higher doses
What can alcohol toxicity result in? (4)
Emesis, coma, respiratory distress, death
Alcohol exhibits effects on what system as a vasodilator resulting in hypothermia and uterus relaxation (can prevent preterm labor)?
Smooth muscle
How does alcohol affect the heart?
↓ contractility (↓ CO/BP)
How does alcohol affect the kidney?
↓ ADH → diuretic effect
How is alcohol toxicity managed? (2)
Manage respiratory depression and prevent emesis
If a pt with alcohol toxicity is having seizures, what is the treatment?
Lorazepam (benzo) and Phenytoin (anticonvulsant)
What is the main cause of a hangover (in addition to dehydration and beginning of withdrawal)?
Buildup of acetaldehyde
What is the general cause of the complications seen with chronic alcohol use/ alcohol tolerance?
Decreased glutathione concentrations = oxidative stress and tissue damage
What are the 3 most common complications associated with chronic alcohol use?
Gastritis, pancreatitis, liver disease
What are the most common liver complications associated with chronic alcohol use? (3)
- Alcoholic hepatitis
- Liver cancer- most likely 10 yrs after stopping alcohol consumption due to liver attempting to heal itself
- Fatty liver → fibrosis → cirrhosis
Chronic alcohol use leads to malnutrition specifically related to what 2 things?
Folate and thiamine
What CNS complication of chronic alcohol use is defined as a thiamine deficiency leading to paralysis of eye muscles, ataxia, confusion, coma/ death?
Wernicke-Korsakoff syndrome
What CNS complication of chronic alcohol use is defined as chronic disabling memory loss?
Korsakoff’s psychosis
Aside from Wernicke-Korsakoff syndrome and Korsakoff’s psychosis, what other CNS complication can be associated with chronic alcohol use?
Peripheral neuropathy
What are the most common CV complications seen with chronic alcohol use? (5)
Cardiomyopathy (toxic effects of acetaldehyde), arrhythmias, HTN, stroke, CHD
How does alcohol affect tobacco use?
Increases carcinogenicity
The following are associated complications of what?
Mild anemia, sexual dysfunction, immune system suppression, skeletal muscle atrophy, hypothermia, teratogenicity
Chronic alcohol use
What is the most effective treatment for alcohol abuse?
Combo of pharm and psychosocial
What is the MOA for Naltrexone? (3)
Opioid receptor antagonist → blocks ability of alcohol to stimulate reward pathway → reduces cravings & relapse
What is the contraindication for Naltrexone?
Liver failure
What is the MOA for Acamprosate? (3)
Structural analogue of GABA → restores normal balance of GABA and glutamate → decreases cravings and relapse
How is Acamprosate excreted?
By kidneys (no liver toxicity)
When should Disulfiram be taken to be effective?
Prior to alcohol consumption
What is the action of Disulfiram? (3)
Inhibits aldehyde dehydrogenase → acetaldehyde builds up → flushing, HA, nausea, confusion (makes drinking alcohol unenjoyable)
Does Disulfiram have a long or short duration of action?
Long
What are the severe effects of Disulfiram? (7)
Vomiting, sweating, chest pain, hypotension, vertigo, blurred vision, shock
(dangerous and not recommended)
What is the MOA for Topiramate?
Anticonvulsant (alcohol role not well understood)
What is the effect of Topiramate?
Decreases craving and increases abstinence in recovering alcoholics
The following are sxs associated with what?
Anxiety, irritability, nausea, tachycardia, insomnia
Mild alcohol withdrawal
The following are sxs associated with what?
Hallucinations, delirium, tremors, seizures, fatal arrhythmias, hypotension
Severe alcohol withdrawal
What is the general treatment for alcohol withdrawal? (non-pharmacologic)
Restore electrolyte imbalances, hydration
What do Diazepam (Valium) and chlordiazepoxide do with respect to treatment of alcohol withdrawal?
Prevent seizures and delirium/ tremors, tapers sxs
What does Lorazepam (Ativan) do with respect to treatment of alcohol withdrawal?
Used to TREAT seizures
What does Phenytoin (Dilantin) do with respect to treatment of alcohol withdrawal?
Secondary drug to TREAT seizures
