MT6314 SUBSTANCE OF ABUSE Flashcards
The primary kind of alcohol which is a substance of abuse is?
ethyl
Occupies an important place in history of mankind
Alcohol
Main alcohol staple of western countries in the 19th century?
Beer and wine
Alcohol is known to be associated with?
acute and chronic
illnesses
Moderate amount of alcohol relieves and provides what?
relieves anxiety and provides feeling of euphoria
The most commonly abused drug in the world
Alcohol
continue consumption despite
suffering consequences
Alcohol abuse
inability to control drinking, devoting much time to getting and using alcohol, or recovering from its effects
Alcohol dependence
use disorders are complex; has genetic and environmental factors
Alcohol
Is ethanol water soluble?
Yes
Where does ethanol absorb rapidly in the body?
gastrointestinal tract
In fasting state, peak blood alcohol concentrations are reached within how long?
30mins
What delays alcohol absorption by slowing gastric emptying?
Food
Alcohol distribution: rapid or slow?
Rapid
Volume of distribution for ethanol approximates?
total body water (0.5–0.7 L/kg)
T or F: Women have a higher peak concentration than men
T
Why do women have a higher peak concentration than men?
Women have a lower total body water content and differences in first-pass metabolism
In CNS, concentration of ethanol rises (slowly/quickly)
Quickly
Why in the CNS, concentration of ethanol rises quickly?
Brain receives a large proportion of total blood flow and ethanol readily crosses biologic membranes
> 90% of alcohol is oxidized in? And the remainder in where?
the liver
remainder excreted through the lungs and in the urine
Excretion by the lungs can be quantified with?
breath alcohol tests
Alcohol Oxidation follows what order of kinetics?
zero-order kinetics
Typical adult can metabolize how many grams of alcohol per hour?
7–10 g (150–220 mmol)
Primary pathway for alcohol metabolism
Alcohol Dehydrogenase Pathway
Where is Alcohol Dehydrogenase Pathway mainly located?
Liver (main), brain, stomach
What about the alcohol dehydrogenase pathway affects the rate of ethanol metabolism and alters vulnerability to alcohol-abuse
disorders?
considerable genetic variation in ADH enzymes
Is metabolism by ADH greater in men or women? and why?
Men bec. of sex-related differences in
blood alcohol concentrations
The Microsomal Ethanol-Oxidizing System (MEOS) uses ____ and consists of _____
uses NADPH, consists
primarily of cytochrome P450 enzyme group
When is MEOS activity induced?
during chronic alcohol
consumption, also when blood levels are >100mg/dL
What happens in chronic alcohol consumption?
significant increases in ethanol metabolism and the clearance of other drugs eliminated by the cytochrome P450s that constitute the MEOS system
Much of the acetaldehyde formed is oxidized in the liver in a reaction is catalyzed by?
Aldehyde dehydrogenase (ALDH)
What is the product of Acetaldehyde Metabolism?
acetate
used to deter drinking by patients with alcohol dependence
Disulfiram
Acetaldehyde accumulates and causes an unpleasant reaction of facial flushing, nausea, vomiting, dizziness, and headache
Disulfiram + Ethanol
Examples of drugs that inhibit ALDH? What od these drugs do?
metronidazole, cefotetan, trimethoprim
Cause a disulfiram-like reaction if combined with ethanol
People of what descent have a genetic deficiency of ALDH?
East Asian descent
What happens to East Asians since they have deficiency in ALDH?
Consuming alcohol, they develop high blood acetaldehyde concentrations and experience a reaction similar to that seen with the combination of disulfiram and ethanol
Asian flush
What effect does alcohol have on the CNS?
sedation, relief of anxiety
At higher concentrations of alcohol, what does it cause to the CNS?
ataxia, impaired judgment, and
disinhibited behavior
Additive CNS depression occurs with concomitant ingestion of?
Ethanol and a variety of CNS depressants such as sedative-hypnotics, opioid agonists, and drugs that block muscarinic and H1 histamine receptors.
Ethanol appears to modulate the function of?
Signaling molecules such as the action of GABA at GABAA receptors, inhibits the ability of glutamate to activate NMDA receptors and modifying the activities of adenylyl cyclase, phospholipase C, and ion channels
What BAC levels leads to sedation and depression of myocardial contractility?
50-100: sedation
>100: depression of myocardial contractility
What BAC levels leads to emesis and stupor?
200-300
What BAC levels leads to coma?
300-400
What BAC levels leads to respiratory depression and death?
> 400
What BAC levels leads to impaired motor function, slurred speech, ataxia?
100-200
Ethanol, in relation to smooth muscles, is also a?
vasodilator
In severe alcohol overdose, what happens to the Smooth muscles?
hypothermia Bec. of vasodilation
What augments the hypotensive effects of ethanol,
may cause severe orthostatic hypotension and syncope?
Flibanserin
T or F: Ethanol also vasodilator the uterus
F, it relaxes it
How does alcohol cause tissue damage?
Oxidative stress with depletion of glutathione, damage to mitochondria, growth factor
deregulation, potentiation of cytokine-induced injury
What kind of tolerance facilitates GABA activity?
Cross-tolerance to sedative-hypnotic drugs
What kind of dependence is seen in chronic alcohol consumption?
Psychological and physical
Most common medical complication that comes with chronic alcohol consumption?
Liver disease
Reduced gluconeogenesis leads to?
Hypoglycemia
Progressive loss of liver function, with reversible fatty liver leads to?
irreversible hepatitis, cirrhosis, and liver failure
In both sexes infected with hepatitis B or C, is hepatic dysfunction more severe in men or women?
Women
Consequences of chronic alcohol consumption on the GI tract?
Irritation, inflammation, bleeding, and scarring of the gut wall
absorption defects and exacerbation of nutritional
deficiencies
increases the risk of pancreatitis
Consequences of chronic alcohol consumption on the CNS?
Peripheral neuropathy
Wernicke- Korsakoff
syndrome
What causes Wernicke- Korsakoff syndrome? and what is it characterized by?
Thiamine deficiency, along with alcohol abuse
characterized by ataxia, confusion, and paralysis of the
extraocular muscles
How to treat Wernicke- Korsakoff syndrome? This treatment is essential to prevent?
Treatment with parenteral thiamine is essential to prevent Korsakoff’s psychosis: a permanent memory disorder
Alcohol withdrawal symptoms with forced quitting/reduction causes?
hyperexcitability in mild cases; seizures, toxic psychosis, and delirium tremens in severe ones
Effects of chronic alcohol consumption to the endocrine system and electrolyte balance?
Gynecomastia and testicular atrophy
Ascites, edema, and effusions
Alterations of whole body potassium
Severe secondary aldosteronism
Hypoglycemia
Effects of chronic alcohol consumption to the cardiovascular system?
Hypertension, anemia, and dilated
cardiomyopathy
Binge drinking = arrhythmia
Modest quantities = HDL goes up
Effects of chronic alcohol consumption to the immune system?
Some immune functions inhibited, some triggered
Lungs: suppressed alveolar macrophage function, inhibition of chemotaxis of
granulocytes, reduced T cells, increases mortality & morbidity of pneumonia
Liver: enhanced function of cells in immune system, increased cytokine production
Chronic alcohol use also leads to increased risk of what cancers?
Cancer of the mouth, pharynx, larynx, esophagus, and liver and small increase of breast cancer in women
What species produced by increased cytochrome P450
activity can damage DNA?
Acetaldehyde and reactive oxygen
What consequence of chronic alcohol consumption has teratogenic effects?
Fetal alcohol syndrome
Most commonly stem from alcohol-induced increases of drug-metabolizing enzymes
Prolonged intake without liver damage can enhance the biotransformation of other drugs
ALCOHOL-DRUG INTERACTIONS
Ethanol-mediated induction of hepatic cytochrome P450 enzymes is particularly important with regard to?
acetaminophen
(Paracetamol)
Chronic or acute alcohol consumption can inhibit metabolism of other drugs - decreased enzyme activity or decreased liver blood flow?
Acute
Examples of drugs whose metabolisms are inhibited with acute alcohol use?
Phenothiazines, tricyclic antidepressants, and sedative- hypnotic
drugs
Occurs when alcohol is combined with other CNS depressants, particularly sedative-hypnotics
Additive CNS depression
What kind of drugs can be used in the management of alcohol withdrawal syndrome?
Long-acting sedative-hypnotic drug replaced for alcohol (Benzodiazepines preferred- chlordiazepoxide, diazepam)
Shorter-acting benzodiazepines- lorazepam and oxazepam
Useful in alcoholic patients with liver disease
lorazepam and oxazepam
Built in tapering effect where active metabolites may accumulate
Long-acting sedative-hypnotic drug replaced for alcohol
Main DRUG TREATMENTS OF ALCOHOLISM
Naltrexone
Acamprosate
Disulfiram
Nicotine & Caffeine effects (common)
cardiovascular, respiratory, and neoplastic disease with smoking
addiction and dependence
Causes respiratory paralysis
Nicotine
Seen in small children who ingest nicotine gum, nicotine patches or vaping solutions
Severe nicotine toxicity
Characterized by excessive CNS stimulation with tremor, insomnia, and nervousness; cardiac stimulation and arrhythmias
Acute toxicity for both nicotine and caffeine
Nicotine is the selective agonist of?
nicotinic acetylcholine receptor
Nicotine is slowly or quickly absorbed?
Slowly
Partial agonist action at α4β2 nicotinic receptors
Varenicline
Effects of varenicline?
may impair the capacity to drive, associated with suicidal ideation
antidepressant is approved for nicotine cessation therapy
Bupropion
When is Bupropion most effective?
when combined with behavioral therapies
agonist at cannabinoid receptors, used off-label in smoking cessation
Rimonabant
Caffeine is a member of what family?
methylxanthine
Effects of caffeine on the heart?
Has positive chronotropic and inotropic effects on the heart
Antidote to caffeine withdrawal?
Esmolol a short-acting β blocker
Inhibits caffeine metabolism
Quinolone
What treatment of alcoholism: long acting opioid antagonist, blocks u-opioid receptors
Naltrexone
What treatment of alcoholism: Can cause dose-dependent hepatotoxicity, used with caution if with abnormal serum aminotransferase activity
Naltrexone
T or F: Naltrexone is usually taken with disulfiram
F, if taken together, will result in hepatotoxicity
What treatment for alcoholism: Has actions on GABA, glutamate, serotonergic, noradrenergic, and dopaminergic receptors
Acamprosate
What treatment for alcoholism: A weak NMDA-receptor antagonist and a GABAA-receptor activator.
Acamprosate
What treatment for alcoholism: Should not be given to patients with severe renal impairment
Acamprosate
What treatment for alcoholism: Inhibits aldehyde dehydrogenase, acetaldehyde accumulates
Disulfiram
Disulfiram inhibits the metabolism of?
Phenytoin
Oral anticoagulants
Isoniazid
What type of alcohol: Used in industrial production of synthetic organic compounds and as a constituent of many commercial solvents, also in windshield-washing products
Methanol/methyl alcohol/wood alcohol
Methanol/methyl alcohol/wood alcohol is oxidized to?
formaldehyde, formic acid, and CO2
Methanol can also cause poisoning from?
Accidental ingestion
Methanol is absorbed well in the?
Skin
Respiratory
GI
Treatment for methanol poisoning?
Respiration support
Modalities of treatment for severe methanol poisoning?
Suppression of metabolism by alcohol dehydrogenase to toxic products
Hemodialysis
Alkalinization
alcohol dehydrogenase inhibitor
Fomepizole
higher affinity than methanol for alcohol dehydrogenase saturation reduces formate production
Intravenous ethanol
Used as heat exchangers, in antifreeze formulations, and as industrial solvents
Ethylene glycol
Stages of overdose of ethylene glycol?
transient excitation followed by CNS depression (first few hours after ingestion)
severe metabolic acidosis (after 4-12 hours)
delayed renal insufficiency
Treatment to ethylene glycol overdose?
fomepizole, ethanol, and hemodialysis
Alcohol has an additive sedative effect with?
Sedative-hypnotics
Alcohol additive vasodilator effect with?
Hypoglycemic agents
Alcohol additive anti-platelet action with?
Aspirin
Ethylene glycol toxicity is retarded by?
Fomepizole or IV ethanol
Alcohol-drug interactions have the induction of?
SER
What treatment for alcohol: NMDA antagonist
Acamprosate
What treatment for alcohol: Opioid antagonist
Naltrexone
What treatment for alcohol: 5-HT3 antagonist
Ondansetron
What treatment for alcohol: Aldehyde dehydrogenase antagonist
Disulfiram
What treatment for alcohol: Mainly targets CNS NTA system
Naltrexone