A. Addiction Management

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Questions and Answers

What is the primary distinction between dependence and addiction?

Dependence occurs with chronic exposure while addiction develops in a small subset of individuals. (correct)

Dependence is characterized by compulsive drug use.

Addiction leads to tolerance while dependence does not.

Addiction involves physical withdrawal symptoms.

Which mechanism is primarily associated with the effects of addictive drugs?

Activation of serotonin pathways.

Inhibition of the GABA receptors.

Increased acetylcholine levels.

Dopamine mechanism activation. (correct)

What is considered a hallmark of addiction?

Physical withdrawal symptoms.

Chronic exposure to substances.

Acute intoxicating effects.

Compulsive drug seeking behavior. (correct)

What does the withdrawal syndrome refer to?

Combination of symptoms occurring after drug cessation. Signup and view all the answers

What is the legally allowed blood ethanol concentration for operating a motor vehicle in the United States?

80 mg% Signup and view all the answers

What is the role of the ERK pathway in drug dependence?

It is activated during chronic drug exposure. Signup and view all the answers

How does tolerance develop with drug use?

As a result of down-regulation or up-regulation by the brain. Signup and view all the answers

What approximate blood ethanol concentration does the consumption of one standard drink produce in a 70-kg person?

30 mg% Signup and view all the answers

Which of the following enzymes is NOT primarily involved in ethanol metabolism?

LDH Signup and view all the answers

What substance is derived from the leaves of Erythroxylum coca?

Cocaine. Signup and view all the answers

What aspect of drug use indicates psychological dependence?

Using the drug to alleviate stress or emotional pain. Signup and view all the answers

How does ethanol primarily exert its sedative effects on the brain?

Through binding to GABA receptors Signup and view all the answers

What is the role of ethanol as an anti-infective agent?

Disrupts osmotic balance Signup and view all the answers

What is the primary mechanism by which cocaine affects neurotransmitter levels?

Inactivates sodium channels and prevents re-uptake of neurotransmitters Signup and view all the answers

Which of the following effects can occur during acute cocaine intoxication?

Euphoria and hyperactive behavior Signup and view all the answers

What is the role of benzodiazepines in managing acute cocaine intoxication?

To reduce anxiety and agitation Signup and view all the answers

Which type of transporter does cocaine primarily target to affect dopamine levels?

Sodium-dependent dopamine transporter Signup and view all the answers

Cocaine's sympathomimetic properties can lead to which of the following outcomes?

Increased cardiac output and vasoconstriction Signup and view all the answers

What precaution should be taken regarding the use of non-selective beta-blockers in cocaine intoxication?

They can worsen cardiovascular complications if myocardial infarction is present. Signup and view all the answers

What is a common sign of cocaine toxicity that relates to kidney function?

Rhabdomyolysis Signup and view all the answers

Which of the following receptor types does cocaine act as an antagonist for?

Muscarinic acetylcholine receptors M1 & M2 Signup and view all the answers

Which system is NOT directly affected by ethanol consumption?

Reproductive system Signup and view all the answers

What is a potential hematologic effect of ethanol?

Anemia Signup and view all the answers

Which of the following is a known teratogenic effect of ethanol?

Cognitive impairment Signup and view all the answers

Ethanol acts as a diuretic. What physiological change does this primarily affect?

Kidney function Signup and view all the answers

What cardiovascular issue is often linked to chronic ethanol use?

Arrhythmia Signup and view all the answers

What was a primary reason for the overproduction of amphetamines during World War II?

To promote wakefulness in soldiers Signup and view all the answers

Which neurotransmitter transporter does amphetamine primarily affect as a modulator?

Sodium-dependent dopamine transporter Signup and view all the answers

Which receptor type does amphetamine NOT act as an agonist for?

Serotonin receptors Signup and view all the answers

What is a common neurologic effect of acute amphetamine toxicity?

Agitation Signup and view all the answers

What mechanism does amphetamine use to displace monoamines?

Retro-transport via VMAT2 Signup and view all the answers

Which of the following is NOT a potential acute effect of amphetamine overdose?

Increased sedation Signup and view all the answers

How does amphetamine typically influence the levels of catecholamines?

Elevates their levels Signup and view all the answers

What is a potential consequence of amphetamine use on the psychotic spectrum?

Triggering of psychotic episodes Signup and view all the answers

Which receptor does nicotine primarily target in its mechanism of action?

Nicotinic-cholinergic receptor Signup and view all the answers

What is the primary effect of nicotine on synaptic transmission?

It blocks synaptic transmission. Signup and view all the answers

What type of molecule is nicotine classified as?

Neuroactive alkaloid Signup and view all the answers

Which neurotransmitter is NOT released by nicotine?

Glutamate Signup and view all the answers

What health risk is associated with nicotine addiction?

Increased risk of severe adverse health effects from tobacco Signup and view all the answers

What is a common use for ethanol aside from being an ingredient in alcoholic beverages?

As a topical disinfectant Signup and view all the answers

Which property of ethanol contributes to its addictive nature?

It has rewarding properties. Signup and view all the answers

Which receptor subunits are primarily associated with nicotine's action?

Alpha-3, beta-2, beta-4 Signup and view all the answers

Study Notes

Drugs of Abuse Management

Objectives: Identify clinical presentation of intoxication and withdrawal syndromes for commonly abused substances in the US. Understand the pathophysiology of these substances. Provide accurate treatment based on the identified substance of abuse.

Dependence vs. Addiction

Tolerance: Adaptive changes in response to repeated drug exposure, requiring higher doses to maintain the same effect.
Addiction: Compulsive, relapsing drug use despite negative consequences, often triggered by cravings.
Dependence: Withdrawal symptoms appear when the abused drug is no longer available; a combination of such signs is called withdrawal syndrome.

Dependence vs. Addiction (Continued)

Physical Dependence is a sign of dependence.
Psychological Dependence is a sign of addiction.
Compulsive drug seeking and relapse are hallmarks of addiction.

Drug Mechanisms

Common Mechanisms: Dopamine (DA) pathways, extracellular signal-regulated kinase (ERK) pathways, decreased calmodulin-related genes, and increased transcription of lipid/cholesterol and Golgi/endoplasmic reticulum (ER) function genes, along with glutamate and GABA receptor activity. These responses are seen across many abused drugs.

Tolerance & Withdrawal

Tolerance: Downregulation/up-regulation of brain adaptation. Repeated exposure to addictive drugs leads to brain adaptation.
Withdrawal: Adaptive changes become apparent once drug exposure ends.

Drugs That Activate G Protein-Coupled Receptors

Opioids Act on μ-OR (Gio) with disinhibition response.
Cannabinoids Act on CB₁R (Gio) with disinhibition response.
GHB Act on GABA_BR (Gio) with weak agonist and disinhibition response.
Other drugs listed in the table.

Drugs That Bind to Ionotropic Receptors and Ion Channels

Nicotine Act on nAChR (α4β2) with excitation response.
Alcohol Act on GABAAR, 5-HT₃R, nAChR, NMDAR, Kir3 channels with excitation and disinhibition.
Other drugs listed in the table.

Cocaine

Source: Alkaloid ester from Erythroxylum coca leaves.
Clinical Use: Local anesthetic and vasoconstrictor.
Mechanism of Action:
- Reversibly binds and inactivates sodium channels.
- Binds differentially to dopamine, serotonin, and norepinephrine transport proteins, preventing their reuptake.
Targets: Sodium-dependent dopamine transporter, noradrenaline transporter, serotonin transporter, sodium channel protein type 5, 10, and 11, and muscarinic acetylcholine receptors M1 & M2.
Effects: Euphoria, hyperactivity, appetite suppression, local anesthesia, and possible sudden death due to cardiac arrest.

Cocaine Continued

Toxicity: Intense agitation, convulsions, hypertension, rhythm disturbance, coronary insufficiency, hyperthermia, rhabdomyolysis, and renal impairment.
Acute Intoxication Management: Benzodiazepines (diazepam), phentolamine. Hyperthermia management: cold water immersion. Consider nitroglycerin for refractory hypertension. Use B-blockers with caution.

Amphetamine Type

Structure: Similar to catecholamines (aromatic ring and nitrogen).
History: Used for wakefulness during World War II, then became restricted.
Common Types: Amphetamine (AMPH), methamphetamine (METH), methylphenidate (MPH), and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)
Mechanism of Action: Taken into presynaptic nerve terminals (with sodium ions and chloride). Actively transported by monoamine reuptake transporters. Displaces other monoamines leading to storage within vesicles and retro-transport.
Targets: Synaptic vesicular amine transporter antagonist, Vesicular monoamine transporter 2 (VMAT2) antagonist, Sodium-dependent dopamine transporter modulator, and Sodium-dependent noradrenaline/serotonin transporter modulators and MAO antagonist, Alpha and Beta adrenergic receptor agonist.
Effects: Elevated catecholamine levels, arousal, reduced sleep, euphoria, abnormal movements, psychotic episodes, effects on serotonin transmission (hallucinogenic), and effects on anorexia and hyperthermia.
Toxicity: Acute amphetamine overdose causes hyperthermia, respiratory depression, seizures, metabolic acidosis, renal failure, hepatic injury, coma, neurologic effects (agitation, hallucinations), cardiovascular effects (arrhythmias, myocardial infarctions), GI tract effects (pain, vomiting), and adrenal medulla/neurotransmission effects.

Amphetamine Type Continued

Factors Leading to Toxicity: Mitochondrial dysfunction, oxidative stress, excitotoxicity, and hyperthermia.
Elimination: Urine (40%–90% within 72 hours), and pH dependent.

Lysergic Acid Diethylamide (LSD)

Mechanism of Action: Activates serotonin 5-HT2A receptors, enhances glutamatergic transmission. Repeated doses result in rapid downregulation.
Target: 5-hydroxytryptamine receptor 1A, 2B, 6 agonist.
Effects: Mood alteration, anxiety, tachycardia, increased blood pressure and body temperature, dizziness, decreased appetite, sweating, loss of judgment.

Marijuana

Components: Cannabis sativa and Cannabis indica; over 400 chemical compounds, including 61 cannabinoids (THC and CBD).
Mechanism of Action: THC acts as a weak partial agonist at cannabinoid-1 (CB1R) and cannabinoid-2 (CB2R) receptors. CBD acts as a negative allosteric modulator of CB1 receptors.
Effects: Increased appetite, reduced pain, and changes in emotional & cognitive processes.

Marijuana Continued

Targets: Cannabinoid receptor 1 & 2 modulator, glycine receptor subunit alpha-1, -3, alpha-1/beta, N-arachidonyl glycine receptor agonist.

Nicotine

Source: Principal neuroactive alkaloid in tobacco.
Mechanism of Action: Binds stereo-selectively to nicotinic cholinergic receptors, stimulating autonomic ganglia and the adrenal medulla, and having effects on the locus ceruleus and limbic system. Results in reward and increased stimulation.
Effects: Stimulation effects, potentially leading to addiction and withdrawal symptoms.
Targets: Neuronal acetylcholine receptor subunit alpha-3, -4, -5, -6, -7, -9, -10; beta-2, -3, -4 agonist. Cytochrome P450 19A1 antagonist, Choline O-acetyltransferase antagonist.

Nicotine Continued

Toxicity: Addiction, adverse health effects.
Mechanisms of Nicotine-Induced Plasticity: Upregulation and downregulation of nAChRs, interactions in catecholaminergic, GABAergic and glutamatergic neurotransmission, and structural changes in specific neural structures.

Ethanol

Characteristics: Clear, colorless liquid readily absorbed from the GI tract, distributed throughout the body and having antibacterial activity (used as topical disinfectant; widely used as solvent and preservative in pharmacy, and as base of alcoholic beverages.)
Mechanism of Action: Affects membranes, ion channels, and various receptor sites (GABA, Glycine, NMDA, Ach, serotonin.) Alters osmolyte balance.
Effects: Reduced inhibition, increased excitation, mesolimbic depression, reduced DA release, dysphoria, anxiety, seizures, confusion, and increased sensitivity to stress.
Absorption: Rapidly absorbed, reaching peak blood levels within 30 minutes.
Metabolism: Primarily metabolized by alcohol dehydrogenase (ADH) in the stomach and liver, followed by other enzymes.
Elimination: 40% eliminated in urine (pH dependent) 72h after oral administration.
Targets: GABA receptor-operated channels, Glycine receptor-operated channels, NMDA receptor-operated channels, Nicotinic ACh receptor-operated channels, Serotonin receptor-operated channels, G-protein couples inwardly rectifying K channels and voltage-gated calcium channels/Large-conductance Ca2+/voltage-activated K channels. (Slo1 containing subunits).
Treatment Medications: Disulfiram (inhibits ALDH), Naltrexone (µ-opioid receptor antagonist), Acamprosate (unknown mechanism, inhibits glutamate state, reduces sensations for alcohol).

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Description

Test your understanding of the clinical presentations of drug intoxication and withdrawal syndromes. This quiz covers the differences between dependence and addiction, as well as the mechanisms of commonly abused substances. Assess your knowledge on effective treatments and intervention strategies.