Neuro (pt 2/4) Alcohol Flashcards
-A sedative-hypnotic with low potency– relieves anxiety and fosters a state of well-being or possibly euphoria at low to moderate amounts
-Most commonly abused drug in the world
-8% of the general population of the USA has an alcohol-use disorder
Alcohol
What is Alcohol abuse?
Utilization of alcohol in dangerous situations (drinking & driving) or continuing to drink alcohol in spite of adverse consequences directly related to their alcohol consumption
What is Alcohol Dependence?
Definition of abuse plus tolerance to alcohol and signs and symptoms of withdrawal; inability to control consumption, obtaining and consuming alcohol is a primary purpose
A small water-soluble molecule that is absorbed rapidly from the GI tract.
Ethanol
Describe peak concentrations of Ethanol for men vs women.
Peak concentrations are reached within 30 minutes.
-Peak within the CNS happens quickly b/c the brain receives a large proportion of total blood flow
-Women peak concentrations faster than men for equivalent consumption due to having a lower total body water content, and differences in 1st pass metabolism.
Where is Ethanol oxidized/excreted?
-90% oxidized in the Liver.
Remainder is excreted through the lungs and in the urine
A family of cytosolic enzymes that catalyze alcohol to acetaldehyde.
-Genetic variation in ADH enzymes that affect the rate of ethanol metabolism and alter vulnerability to alcohol disorders
Alcohol dehydrogenase
How does Alcohol Dehydrogenase metabolize Ethanol?
Alcohol dehydrogenase uses NAD as a cofactor.
-Hydrogen ion is transferred to cofactor, get NADH.
-Ethanol is metabolized to acetaldehyde.
How does the Microsomal Ethanol-Oxidizing system (MEOS) metabolize Ethanol?
-Uses NADPH as a cofactor in metabolism of ethanol.
-Consists of CYP enzymes.
-During chronic alcoholism, MEOS activity is induced, and increased metabolism of any substance that is reliant on CYP 450.
What is the end product of Ethanol metabolism by Alcohol Dehydrogenase or MEOS?
Acetaldehyde (not final step though)
Where is Acetaldehyde metabolized?
End product of Ethanol metabolism is acetaldehyde, which is oxidized in the liver to acetate.
-Acetate is further metabolized to CO2 and water, or used to form Acetyl-CoA.
What drug inhibits alcohol dehydrogenase?
Fomepizole
What enzyme converts Acetaldehyde to Acetate?
Aldehyde dehydrogenase
What drug inhibits aldehyde dehydrogenase?
Disulfiram
How does Disulfiram deter drinking in chronic drinking or dependence?
Buildup of acetaldehyde leads to facial flushing, nausea, sick, etc. Negative feedback deters activity.
A drug that inhibits aldehyde dehydrogenase, so alcohol is metabolized as usual, but acetaldehyde accumulates.
-Rapidly absorbed, elimination is slow (several days)
-Small increases in LFTs
-Teratogenicity unknown
-Causes extreme discomfort in patients who drink alcoholic beverages
Disulfiram
Disulfiram inhibits the metabolism of what other drugs?
-Phenytoin, oral anti-coags, isoniazid
-Should not be given with other meds that contain alcohol
What are S/sx of a Disulfiram reaction?
-Flushing, throbbing headaches, N/V, sweating, hypotension, and confusion
-Lasts 30 min in mild cases and several hours in severe cases
A Long acting opioid receptor antagonist
-Blocks the effects at the mu opioid receptors (blocks happy effects from alcohol)
-Inhibits self administration of alcohol
-PO or IM
-Dose-dependent hepatotoxicity
-Do not administer with Disulfiram
-Adherence is favorable for relapse prevention and tx of alcohol depdendence.
Naltrexone
T/F: You can administer Naltrexone to patients with opioid dependence.
FALSE; do not admin to pts with opioid dependence
A drug utilized in Europe for the treatment of alcoholism. Did not show statistically significant effects alone or in combo with Naltrexone
Acomprosate
What other meds are used Off Label to reduce cravings in chronic alcoholism?
-Ondansetron (Zofran)
-Topiramate (Topamax)
-Baclofen
How do you treat Alcohol Withdrawal?
Motor agitation, insomnia, and reduction of seizure threshold
What are the S/sx associated with Alcohol Withdrawal at 6-8 hours?
Increased BP, tremor, anxiety, and insomnia
-Usually lessens after 1-2 days
What are you at risk for from 1-5 days of Alcohol Withdrawal?
Risk of seizures and hallucinations
Anxiety and sleep disturbances associated with Alcohol Withdrawal can persist for ______.
Several months
When do DT’s begin?
48-72 hours after alcohol cessation
Can last 5-10 days
What are the symptoms of Delirium Tremons (DT’s)?
Delirium, agitation, ANS instability, low-grade fever, diaphoresis
What is the drug therapy for Alcohol Withdrawal?
-Correct electrolyte imbalances (K, Mg, Phos)
-A long acting sedative-hypnotic (Benzos) - such as Chlordiazepoxide (Librium) or Diazepam (Valium)
A patient with decreased Liver Function and is experiencing acute alcohol withdrawal requires the use of____?
-Due to the active metabolites of benzos in the presence of compromised liver function, you should use a short-acting Benzo in a patient with Liver Dz.
-Lorazepam (Ativan)
-Oxazepam (Serax)
What are the CNS effects of Acute Alcohol Consumption?
Sedation
Relief of anxiety
Slurred Speech
Ataxia
Impaired judgment
Disinhibited behavior
Tolerance develops after a couple of hours
Alcohol is a CNS depressant that affects a large number of membrane proteins.
What are the CNS effects of Chronic Alcohol Consumption?
-Dementia
-Withdrawal is associated with seizures, toxic psychosis DT’s
-Wernicke-Korsakoff Syndrome
-Bilat symmetric impaired visual acuity with painless blurring – leading to optic nerve degeneration
What is the effect of acute alcohol intoxication of neurotransmitters (GABA and Glutamate)?
-Enhances action of GABA at GABA Alpha Receptors (GABA Alpha antagonists can attenuate some of alcohols effects)
-Blocks glutamate action on the NMDA receptor (reason for why people black out)
What is the effect of Chronic Alcohol consumption on tolerance and physical/psychological dependence?
-A limit to tolerance so that only a small increase in lethal dose occurs with increased use
-Tolerance may result from up-regulation of neural pathway and Dependence may result from over activity of that same pathway after ethanol dissipates
What is Wernicke-Korsakoff Syndrome?
-Paralysis of the external eye muscles, ataxia, and confusion that can progress to coma and death
-Rare
-Caused by Thiamine deficiency
-A complication of chronic alcohol consumption
What is the effect of Chronic Alcohol Consumption on the Peripheral Nervous System?
-Generalized symmetric peripheral nerve injury
-Distal paresthesias of hands and feet
-Degenerative changes resulting in gait disturbances and ataxia
What is the effect of Acute Alcohol Consumption on the CV system?
-Significant depression of myocardial contractility at BAC > 100mg/dl
-Vasodilation 2/2 CNS effects (depression of the vasomotor center) and direct smooth muscle relaxation of its metabolite (acetaldehyde)
-Vasodilation can be marked in cold environments
What is the effect of Chronic Alcohol Consumption on the CV system?
-Dilated cardiomyopathy
-Ventricular hypertrophy
-Fibrosis
-Ethanol interferes with the therapeutic effects of beta blockers
-Atrial and ventricular arrhythmias
-HTN
-Prevents CAD 2/2 ethanol’s ability to raise HDL
What is the effect of Acute Alcohol Consumption on the Reproductive system?
Relaxes the uterus and was once used IV to suppress premature labor
What is the effect of Chronic Alcohol Consumption on the Reproductive system?
-Gynecomastia
-Testicular atrophy
-Leading cause of mental retardation and congenital malformation (fetus cannot metabolize ethanol)
-Fetal Alcohol Syndrome – ethanol crosses the placenta and the fetus must rely on mom’s enzymes for elimination
What is the effect of Chronic Alcohol Consumption on the GI system?
-Liver disease is the most common complication
-Women are more susceptible to hepatotoxicity than men
-Tumor necrosis factor-α (proinflammatory cytokine) plays a significant role in alcohol associated liver disease
-Common cause of chronic pancreatitis (Alcoholism promotes the formation of protein plugs and calcium carbonate stones)
-Gastritis
-Small intestine damage (D, wt loss & MVI deficiencies)
What is the effect of Chronic Alcohol Consumption on the Blood?
-Mild anemia related to folic acid deficiency
-Iron deficiency anemia may result from GI bleed
-Implicated as a cause of several hemolytic syndromes
What is the effect of Chronic Alcohol Consumption on the Endocrine System & Electrolytes?
-Disruption in steroid hormone balance
-Ascites, edema, and effusions
-Hypoglycemia
-Ketosis
Other misc. effects of Chronic Alcohol Consumption on the body
-Organ & tissue damage r/t the direct effects of ethanol and acetaldehyde and the metabolic consequences of a marked amount of metabolic byproducts
-Increased oxidative stress
-Depletion of glutathione (Avoid Tylenol!!!)
-Damage to mitochondria
-Growth factor dysregulation
-Potentiation of cytokine induced injury
-Associated with increase infections, especially of the lungs and increase the M&M of pts with pneumonia
-Increases the risk of cancer of the mouth, pharynx, larynx, esophagus and liver r/t metabolites
Alcohol can potentiate the effects of many nonsedative drugs including _____ & ______.
vasodilators and oral hypoglycemics
T/F: Alcohol has an additive effect with sedatives/hypnotics
True
Acute alcohol consumption requires ____ anesthesia, while chronic consumption requires _____.
Less; more
Expect _____ on induction for both acute and chronic alcohol consumption due to vasodilation.
Hypotension
Acute consumption of alcohol inhibits the metabolism of what other drugs due to decreased enzyme activity or decreased liver blood flow?
-Phenothiazine
-Tricyclic antidepressants
-Sedative-hypnotics
Prolonged (chronic) alcohol intake without liver damage can _____ the metabolism of other drugs.
enhance
T/F: Acetaminophen metabolism is greatly affected by ethanol mediated increases in CYP activity
True
Why does the risk of hepatotoxicity increase from acetaminophen use with alcohol use?
Consumption of 3 or more alcoholic drinks/day increases the risk of hepatotoxicity from therapeutic high or toxic levels of acetaminophen, due to acetaminophen’s hepatotoxic metabolites (glutathione depletion)
Describe the different Blood Alcohol Concentrations and their Clinical Effects.
50-100: Sedation, subjective “high”, slower rxn time
100-200: impaired motor function, slurred speech, ataxia
200-300: emesis, stupor
300-400: coma
>400: respiratory depression, death
T/F: You would want to induce alcohol intoxication patient with RSI and Cricoid Pressure
True
