8.2 Substance of Abuse Flashcards
Generalities:
● Water soluble
● Rapidly absorbed (GI Tract)
● Primary form of Alcohol
● Rapid distribution (tissue)
● Volume of Distribution: 0.5-0.7 L/kg
Ethanol
What is the peak blood alcohol concentration in fasting state?
30 minutes
What is the peak blood alcohol concentration with food?
Delayed
(slow gastric emptying)
Metabolism of Alcohol:
What is the pathway of alcohol dehydrogenase pathway (primary)?
- ADH
- Located in liver, brain, stomach
- Rate of metabolism
- Vulnerability to alcohol-abuse disease
- Occurs in more in the stomach in men
Metabolism of Alcohol:
What is the pathway of Microsomal Ethanol-Oxidizing System (MEOS)?
- NADPH (cytochrome P450 enzyme)
- ABL: >100 mg/dL
- Chronic alcohol consumption (increases ethanol metabolism and clearance)
- More toxic byproducts
True or False:
In acetaldehyde metabolism, much of the acetaldehyde formed is catalyzed by aldehyde dehydrogenase (ALDH).
True
What is the product of the reaction of acetaldehyde dehydrogenase?
Acetate
Acetaldehyde Metabolism:
This is used to deter drinking by patients with alcohol dependence.
Disulfiram
Acetaldehyde metabolism:
Ethanol + Disulfiram = ?
- increases acetaldehyde = unpleasant reaction
- facial flushing, nausea, vomiting, dizziness, headache
Acetaldehyde metabolism:
What are the other drugs that inhibit ALDH?
- Metronidazole
- Cefotetan
- Trimethoprim
Acetaldehyde metabolism:
Some people of East Asian descent, have genetic deficiency of ALDH where they develop high blood acetaldehyde concentration and strongly protective against alcohol-use disorders.
Asian flush
What are the acute alcohol consumption in CNS?
- Sedation, anxiety relief
- High concentration: intoxidation or drunkenness
- High blood conc: coma, respiratory depression, death
- Signaling molecules effects: inc. GABA, decreased NMDA, adenylyl cyclase, PLc, ion channels
What are the acute aclohol consumption in the heart?
- Decreased myocardial contractility
- > 100 mgdL
What are the acute alcohol consumption in the smooth muscle?
- Vasodilator
- Hypothermia (marked in cold environments)
- Fibanserin: hypotensive effects, orthostatic hypotension, syncope
- Uterus relaxation
Clinical effects of blood alcohol concentration (BAC):
50-100 mg/dL
Sedation, subjective “high”, slower reaction times
Clinical effects of blood alcohol concentration (BAC):
100-200 mg/dL
Impaired motor function, slurred speech, ataxia
Clinical effects of blood alcohol concentration (BAC):
200-300 mg/dL
Emesis, stupor
Clinical effects of blood alcohol concentration (BAC):
300-400 mg/dL
Coma
Clinical effects of blood alcohol concentration (BAC):
500 mg/dL
>400 mg/dL
Respiratory depression, death
What is the tolerance, dependence in the chronic alcohol consumption?
- CNS adaptation and increase rate of ethanol metabolism
- Cross tolerance to sedative-hyptonic drugs (GABA)
- Psychological and physical dependence
What are the chronic alcohol consumption in the liver?
- Liver disease
- Reduced gluconeogenesis -> hypoglycemia
- Reversible fatty liver -> hepatitis, cirrhosis, liver failure
- Hepatic dysfunction (sever in women)
- Loss of function
What are the chronic alcohol consumption in the gastrointestinal system?
- Irritation, inflammation, bleeding, and scarring absorption defects
- Nutritional deficiencies
- Increased risk of pancreatitis
What are the chronic alcohol consumption in the CNS?
- Peripheral neuropathy
- Wernicke-Korsakoff syndrome: thiamine deficiency
- Withdrawal symptoms (delirium tremens)
What are the acute alcohol consumption in the endocrine system and electrolyte balance?
- Gynecomastia
- Testicular atrophy
- Disorders of fluid and electrolyte balance
- Alteration of whole body potassium
- Severe secondary aldosteronism
- Hypoglycemia: hepatic gluconeogenesis
- Cortisol, GH: fluid and electrolyte imb
What are the chronic alcohol consumption in the cardiovascular system?
- Hypertension
- Anemia
- Dilated cardiomyopathy
- Arrhythmia (binge)
- Increase HDL (moderate)
What are the acute alcohol consumption in the immune system in the lungs?
- Macrophage
- Chemotaxis of granulocytes
- Reduced number of T cells
What are the acute alcohol consumption in the immune system in the liver?
- Innate immune system (Kupffer cells, hepatic stellate)
- Increase cytokine prod
What are the increased risks of cancer in acute alcohol consumption?
- Increased P450 activity = damaged DNA
- Cancer mouth, pharynx, larynx, esophagus, liver
- Small risk of breast cancer
- Changes in folate metabolism and growth-promoting effects of chronic inflammation
What are the fetal alcohol syndrome in chronic alcohol consumption?
- Mental retardation
- Growth deficiency
- Microencephaly
- Underdevelopment of midface region
- Congenital heart defect
Alcohol drug interaction:
- Ethanol induction of Hepatic P450 enzyme
- Increase hepatoxicity risk
- Increase P450 mediated conversion: reactive hepatotoxic metabolites
Acetaminophen
Alcohol drug interaction:
- Inhibit metabolism of drugs
- Decreased enzyme activity
- Decreased liver blood flow
Phenothiazines, TCA, Sedative-hypnotics
+Acute alcohol use
Alcohol drug interactions:
Addictive CNS depression
Sedative-hypnotics
Alcohol drug interaction:
Potentiates effects of many non-sedative drugs
Vasodilators/Oral Hypoglycemic agents
True or False:
In managing acute alcohol intoxication, it should prevent respiratory depression and asipiration of vomitus.
True
In managing acute alcohol intoxication, what is considered fatal in blood alcohol concentration?
> 400 mg/dL
What is needed to manage hypoglycemia and ketoacidosis in acute alcohol intoxication?
Glucose
What is needed as prophylaxis against Wernicke-Korsakoff syndrome?
Thiamine and Vit B1
True or False:
In managing alcohol withdrawal, the discontinuance would lead to insomnia, tremor, anxiety, delirium and delirium tremens.
True
What are the long-acting (tapering effect) sedative-hypnotic drug replaced for alcohol?
- Chlordiazepoxide
- Diazepam
Both are benzodiazepines.
What is are the short-acting (convert to water soluble) sedative-hypnotic drug replaced for alcohol?
Lorazepam and Oxazepam
Both are benzodiazepines.
Determine what drug in treating alcoholism:
- Long-acting opioid antagonist, blocks μ-opioid receptors
- Reduces the rate of relapse to either drinking or alcohol dependence
- Reduces craving for alcohol, especially with high adherence
- Dose-dependent hepatotoxicity, used with caution if with abnormal serum aminotransferase activity
- Not given with disulfiram to avoid hepatotoxicity
Naltrexone
Determine what drug in treating alcoholism:
- Molecular effects including actions on GABA, glutamate, serotonergic noradrenergic, and dopaminergic receptors
- Weak NMDA-receptor antagonist and a GABAA-receptor activator
- Widely distributed and is eliminated renally
- Does not appear to participate in drug-drug interactions
- Most common adverse effects are gastrointestinal
- Should not be given to patients with severe renal impairment
Acamprosate
Determine what drug in treating alcoholism:
- Inhibits ALDH, acetaldehyde accumulate
- Flushing, throbbing headache, nausea, vomiting, sweating, hypotension, and confusion occur effects may last 30 minutes to several hours
- Rapidly and completely absorbed from the gastrointestinal tract
- Slow elimination, and action may persist for several days
- Inhibits the metabolism of many other therapeutic agents
- Inhibits the metabolism of: Phenytoin, oral anticoagulants, and isoniazid
- Should not be administered with medications that contain alcohol
- Can cause small increases in hepatic transaminases
Disulfiram
Determine what drug in treating alcoholism:
- Used in industrial production of synthetic organic compounds and as a constituent of many commercial solvents, also in windshield-washing products
- Poisonings from accidental ingestion
- Visual dysfunction, GI distress, shortness of breath, loss of consciousness, and coma
- Absorbed through the skin, respiratory or GI tract and distributed in body water
- Oxidized to formaldehyde, formic acid, and CO2
- Susceptibility of humans to methanol toxicity is due to metabolism to formate and formaldehyde
Methanol/methyl alcohol/wood alcohol
Determine what drug in treating alcoholism:
Alcohol dehydrogenase inhibitor
Fomepizole
Determine what drug in treating alcoholism:
higher affinity than methanol for alcohol dehydrogenase saturation reduces formate production
Intravenous ethanol
Determine what drug in treating alcoholism:
- Used as heat exchangers, in antifreeze formulations, and as industrial solvents
- Young children and animals are attracted by the sweet taste
- Ingested intentionally as an ethanol substitute or in attempted suicide
- Relatively harmless, eliminated by the kidney, metabolized to toxic aldehydes and oxalate
- Fomepizole, ethanol, hemodialysis
Ethylene glycol
What are the effects of nicotine & caffeine?
- High incidence of cardiovascular, respiratory, and neoplastic disease with tobacco smoking
- May cause addiction and dependence
What are the acute toxicity of nicotine & caffeine?
- excessive CNS stimulation with tremor
- insomnia
- nervousness; cardiac stimulation and arrhythmias
What are the toxicity in nicotine?
Respiratory paralysis
True or False:
Ingestion of nicotine gum, nicotine patches or vaping solutions has severe nicotine toxicity in small children.
True
Identify if Nicotine or Caffeine:
Selective agonist of the acetylcholine receptor.
Nicotine
Identify if Nicotine or Caffeine:
The withdrawal is mild, involved irritability, anxiety and sleep problems.
Nicotine
Identify if Nicotine or Caffeine:
Among the most addictive drugs, relapse after attempted cessation is common.
Nicotine
Identify if Nicotine or Caffeine:
Member of the methylxanthine family, and has as the most marked central nervous system effects.
Caffeine
Identify if Nicotine or Caffeine:
Cause mild cortical arousal with increased alertness and deferral of fatigue, and has positive chronotropic and inotropic effects on the heart.
Caffeine
Identify if Nicotine and Caffeine:
The withdrawal causes lethargy, irritability, and headache.
Caffeine
Identify if Nicotine or Caffeine:
Antidote: Esmolol (short-acting β blocker).
Caffeine
Identify if Nicotine or Caffeine:
Intake during nursing is moderately safe.
Caffeine
Identify if Nicotine or Caffeine:
Quinolone antibiotics inhibit its metabolism.
Caffeine
Identify drugs when treating nicotine:
A partial agonist action at α4β2 nicotinic receptors and may impair the capacity to drive, associated with suicidal ideation.
Varenicline
Identify drugs when treating nicotine:
An antidepressant is approved for nicotine cessation therapy. Most effective when combined with behavioral therapies.
Bupropion
Identify drugs when treating nicotine:
Agonist at cannabinoid receptors, used off-label in smoking cessation.
Rimonabant
