8.2 Substance of Abuse Flashcards by Margaux Amaro

Q

Generalities:

● Water soluble
● Rapidly absorbed (GI Tract)
● Primary form of Alcohol
● Rapid distribution (tissue)
● Volume of Distribution: 0.5-0.7 L/kg

A

Ethanol

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Q

What is the peak blood alcohol concentration in fasting state?

A

30 minutes

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Q

What is the peak blood alcohol concentration with food?

A

Delayed
(slow gastric emptying)

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Q

Metabolism of Alcohol:

What is the pathway of alcohol dehydrogenase pathway (primary)?

A

ADH
Located in liver, brain, stomach
Rate of metabolism
Vulnerability to alcohol-abuse disease
Occurs in more in the stomach in men

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Q

Metabolism of Alcohol:

What is the pathway of Microsomal Ethanol-Oxidizing System (MEOS)?

A

NADPH (cytochrome P450 enzyme)
ABL: >100 mg/dL
Chronic alcohol consumption (increases ethanol metabolism and clearance)
More toxic byproducts

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Q

True or False:

In acetaldehyde metabolism, much of the acetaldehyde formed is catalyzed by aldehyde dehydrogenase (ALDH).

A

True

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Q

What is the product of the reaction of acetaldehyde dehydrogenase?

A

Acetate

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Q

Acetaldehyde Metabolism:

This is used to deter drinking by patients with alcohol dependence.

A

Disulfiram

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Q

Acetaldehyde metabolism:

Ethanol + Disulfiram = ?

A

increases acetaldehyde = unpleasant reaction
facial flushing, nausea, vomiting, dizziness, headache

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Q

Acetaldehyde metabolism:

What are the other drugs that inhibit ALDH?

A

Metronidazole
Cefotetan
Trimethoprim

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Q

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.

A

Asian flush

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Q

What are the acute alcohol consumption in CNS?

A

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

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Q

What are the acute aclohol consumption in the heart?

A

Decreased myocardial contractility
> 100 mgdL

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Q

What are the acute alcohol consumption in the smooth muscle?

A

Vasodilator
Hypothermia (marked in cold environments)
Fibanserin: hypotensive effects, orthostatic hypotension, syncope
Uterus relaxation

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Q

Clinical effects of blood alcohol concentration (BAC):

50-100 mg/dL

A

Sedation, subjective “high”, slower reaction times

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Q

Clinical effects of blood alcohol concentration (BAC):

100-200 mg/dL

A

Impaired motor function, slurred speech, ataxia

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Q

Clinical effects of blood alcohol concentration (BAC):

200-300 mg/dL

A

Emesis, stupor

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Q

Clinical effects of blood alcohol concentration (BAC):

300-400 mg/dL

A

Coma

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Q

Clinical effects of blood alcohol concentration (BAC):

500 mg/dL

>400 mg/dL

A

Respiratory depression, death

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Q

What is the tolerance, dependence in the chronic alcohol consumption?

A

CNS adaptation and increase rate of ethanol metabolism
Cross tolerance to sedative-hyptonic drugs (GABA)
Psychological and physical dependence

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Q

What are the chronic alcohol consumption in the liver?

A

Liver disease
Reduced gluconeogenesis -> hypoglycemia
Reversible fatty liver -> hepatitis, cirrhosis, liver failure
Hepatic dysfunction (sever in women)
Loss of function

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Q

What are the chronic alcohol consumption in the gastrointestinal system?

A

Irritation, inflammation, bleeding, and scarring absorption defects
Nutritional deficiencies
Increased risk of pancreatitis

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Q

What are the chronic alcohol consumption in the CNS?

A

Peripheral neuropathy
Wernicke-Korsakoff syndrome: thiamine deficiency
Withdrawal symptoms (delirium tremens)

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Q

What are the acute alcohol consumption in the endocrine system and electrolyte balance?

A

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

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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