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Questions and Answers
The ______ divides substance-related disorders into: (1) substance use disorders (e.g., addiction) and (2) substance-induced disorders (e.g., intoxication, withdrawal, and substance-induced mental disorders).
The ______ divides substance-related disorders into: (1) substance use disorders (e.g., addiction) and (2) substance-induced disorders (e.g., intoxication, withdrawal, and substance-induced mental disorders).
Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
Which of the following terms are characterized by one or more of the five Cs: chronicity, impaired control over drug use, compulsive use, continued use despite harm, and craving?
Which of the following terms are characterized by one or more of the five Cs: chronicity, impaired control over drug use, compulsive use, continued use despite harm, and craving?
Which of the following is NOT a central nervous system depressant?
Which of the following is NOT a central nervous system depressant?
What is the mechanism of action for alcohol?
What is the mechanism of action for alcohol?
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Clinical effects and toxicity management of amphetamines are similar to cocaine.
Clinical effects and toxicity management of amphetamines are similar to cocaine.
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Which of the following treatment strategies is typically used to treat intoxication?
Which of the following treatment strategies is typically used to treat intoxication?
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What is the aim of treating drug dependence?
What is the aim of treating drug dependence?
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Which of the following medications is typically used for alcohol detoxification?
Which of the following medications is typically used for alcohol detoxification?
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What is the mechanism of action for disulfiram?
What is the mechanism of action for disulfiram?
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Which of the following medications is considered a partial agonist that binds selectively to nicotinic acetylcholine receptors, producing a lesser response than nicotine?
Which of the following medications is considered a partial agonist that binds selectively to nicotinic acetylcholine receptors, producing a lesser response than nicotine?
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Which of the following medications is used for smoking cessation but is contraindicated in patients with a current history of seizure disorders?
Which of the following medications is used for smoking cessation but is contraindicated in patients with a current history of seizure disorders?
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Which of the following is not commonly used for smoking cessation?
Which of the following is not commonly used for smoking cessation?
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Treatment for drug dependence is primarily behavioral and a lifelong process.
Treatment for drug dependence is primarily behavioral and a lifelong process.
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What are the primary goals of treating alcohol dependence?
What are the primary goals of treating alcohol dependence?
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Study Notes
Pharmacological Treatments of Addiction
- Lecture 12, Psychopharmacology (CPY 490)
- Objectives: Describe drug use disorders, commonly abused drugs, their mechanism of action and effects, and describe treatments of drug-related disorders (intoxication, withdrawal, and dependence)
Substance-Related Disorders
- DSM-5 classifies substance-related disorders into:
- Substance use disorders (e.g., addiction)
- Substance-induced disorders (e.g., intoxication, withdrawal, substance-induced mental disorders)
Substance-Related Disorders (continued)
- Addiction: Characterized by chronicity, impaired control of drug use, compulsive use, continued use despite harm, and craving.
- Intoxication: A substance-specific syndrome caused by recent substance ingestion and presence in the body.
- Physical dependence: A state of adaptation manifested by a drug class-specific withdrawal syndrome, produced by abrupt cessation.
- Tolerance: A reduction in drug's effects over time due to adaptation from drug exposure
Commonly Abused Substances
- Central nervous system depressants: Alcohol, Benzodiazepines, Opiates (Heroin, Hydrocodone)
- Central nervous system stimulants: Cocaine, Amphetamines (Methamphetamine)
- Hallucinogens: Marijuana/Hashish, Cannabinoids
- Other substances: Nicotine
Neurological Model of Drug Addiction
- Activation of reward mesolimbic dopaminergic pathway (acute mechanism).
- Most significant pathway: Ventral tegmental area (VTA) to nucleus accumbens (NAC) via dopamine.
- Other pathways: Include emotional and memory processing in the frontal cortex.
- Addictive drugs increase dopamine release in the brain's reward regions promoting repeated intake, leading to addiction.
- Adaptation occurs following prolonged exposure.
Mechanisms of Drug Abuse
- Direct effects: Drugs increase dopamine transmission by inhibiting reuptake or causing direct dopamine release.
- Indirect effects: Drugs inhibit GABA, which indirectly increases dopamine release.
- Other neurotransmitters : Serotonin has hallucinogenic effects.
Mechanisms of Drug Abuse (Opiates)
- Opiates bind to opiate receptors on presynaptic neurons, inhibiting GABA (inhibitory of dopamine), leading to massive dopamine efflux into the synaptic cleft.
Mechanisms of Drug Abuse (Benzodiazepines and Barbiturates)
- Benzodiazepines and barbiturates activate GABA-A receptors, reducing GABA release. This disinhibits dopamine, increasing dopamine levels.
Alcohol
- Also known as ethanol, the most commonly abused substance.
- Mechanism of action: Enhances the effects of the inhibitory neurotransmitter GABA, acting as a CNS depressant.
- High doses can cause coma and respiratory depression.
- Withdrawal symptoms exist.
- Chronic alcohol abuse linked to severe health effects: cardiomyopathy, fatty liver, alcoholic hepatitis, cirrhosis, myopathy, pancreatitis, testicular atrophy (males), fetal alcohol syndrome, and spontaneous abortion (females).
Cocaine
- CNS stimulant with low oral bioavailability.
- Often snorted, solubilized, or injected (crack cocaine can be smoked).
- Effects include euphoria, agitation, tachycardia, hypertension, respiratory failure, hyperthermia, chest pain, convulsion.
Amphetamines
- CNS stimulants with clinical effects and toxicity management similar to cocaine.
Treatments of Drug-Related Disorders
- Treat intoxication (e.g., overdose): Use antagonists (antidotes) to reverse substance effects; only if necessary, symptomatic.
- Treat withdrawal symptoms: Use agonists for longer duration, and milder withdrawal; gradual discontinuation.
- Treat dependence: Aim to prevent relapse through anti-craving medications.
Treatments of Intoxication
- Avoid drug therapy if possible.
- Drug therapy might be needed if patients are agitated, combative, or psychotic, usually through IV/IM medications for short-term use (few doses)
- Immediate toxicology screening (blood or urine).
Treatments of Intoxication (Benzodiazepines and Opiates Overdose)
- Benzodiazepine overdose :Flumazenil, Caution: not for all cases, risks of seizures, precipitates withdrawal.
- Opiate intoxication: Naloxone, Use to revive patients with respiratory depression, precipitates withdrawal.
Treatments of Intoxication (Cocaine and Hallucinogens)
- Cocaine intoxication: Pharmacologic treatment only if patient is agitated or psychotic, use lorazepam, antipsychotics, treat seizures supportively.
- Hallucinogen intoxication: reassurance, antianxiety and/or antipsychotic medications.
Treatment of Withdrawal from Drugs of Abuse
- Alcohol: Maintain fluids and electrolyte balance, vitamin deficiencies; benzodiazepines (lorazepam preferred) during detoxification.
- Alcohol withdrawal seizures: Supportive care unless they progress to status epilepticus.
- Benzodiazepine withdrawal: Use the same drugs and dosages as used for alcohol withdrawal (lorazepam).
- Opiates: Methadone, synthetic opiate, taper dosing. Clinicians use schedules of 30–180 days.
Treatments of Substance Use Disorders
- Primarily behavioral-based.
- Lifelong process aiming to prevent relapses, commonly done using anti-craving treatment methods.
Treatment of Alcohol Dependence
- Medications: Disulfiram (Antabuse), Naltrexone, Acamprosate, antidepressants, mood stabilizers.
- Disulfiram: Deterrent, averse reaction upon alcohol consumption.
- Naltrexone/Others: Anti-craving medication, usually for long-term maintenance.
Disulfiram
- Inhibits aldehyde dehydrogenase, prolonging alcohol metabolism.
- Requires close monitoring of liver function especially in patients with hepatic disorders.
Naltrexone
- Opioid antagonist, reducing craving and drinking days.
- Contraindicated for currently opioid-dependent patients as it can induce withdrawal.
- Monthly intramuscular (depot) formulation for long-term use. Liver failure and hepatitis patients need close observation.
Treatment of Nicotine
- First line treatments- Bupropion sustained release, Nicotine Replacement Therapy (nicotine gum, inhaler, lozenge, nasal spray, patch), Varenicline.
- Second line treatments- Nortriptyline if first line treatments fail.
Bupropion
- Antidepressant. Contraindicated in patients with seizure disorder, anorexia nervosa, or recent use of monoamine oxidase inhibitors (within 14 days).
- Caution concerning concurrent use with other medications that lower seizure threshold.
Varenicline
- Partial nicotinic acetylcholine receptor agonist.
- Prescribed for 12 weeks; a second 12-week treatment may be needed for failure.
- Can result in higher cessation rates than bupropion.
- Behavioural adverse effects and cardiovascular events are potential side effects.
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