Lecture 12: Pharmacological Treatments of Addiction PDF

Pharmacological treatemnts of addiction Lecture 12 1446 H Psychopharmacology (CPY 490) Lecture objectives By the end of this session, you will be able to: Describe drug use disorders, commonly abused drugs, their mechansim of action and effects. Describe...

Pharmacological treatemnts of addiction Lecture 12 1446 H Psychopharmacology (CPY 490) Lecture objectives By the end of this session, you will be able to: Describe drug use disorders, commonly abused drugs, their mechansim of action and effects. Describe treatments of drug-related disorders including intoxication, withdrawal and dependence. 2 Substance-Related Disorders The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) divides substance-related disorders into: (1) substance use disorders (e.g., addiction). (2) substance-induced disorders (eg, intoxication, withdrawal, and substance-induced mental disorders). 3 Substance-Related Disorders Addiction: Characterized by one or more of the following five Cs: chronicity, impaired control over drug use, compulsive use, continued use despite harm, and craving. Intoxication: Development of a substance-specific syndrome after recent ingestion and presence in the body of a substance. Physical dependence: A state of adaptation manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation. Tolerance: a reduction in drug’s effects over time as a result of adaptation due to exposure to a drug. 5 Commonly abused substances Central nervous system depressants: Alcohol Benzodiazepines and other sedative-hypnotics Opiates (most commonly heroin, hydrocodone) Central nervous system stimulants: Cocaine Amphetamines (e.g, methamphetamine) Hallucinogens: Marijuana/hashish Cannabinoid Other substances: Nicotine 6 Neurological model of drug addiction Activation of reward mesolimbic dopaminergic pathway in the brain (acute mechanism). Most important pathway: VTA>dopamine>Nac (nucleus accumbens). Other pathways: frontal cortex (emotions and memories). All known addictive drugs activate reward regions in the brain by causing a sharp increase in the release of dopamine. This promotes repeated drug intake and leads eventually to addiction. Adaptation after chronic exposure. 8 Mechanisms of drug abuse Drugs of abuse can: Directly increase dopamine transmission (by inhibiting the reuptake, or cause release of dopamine). Indirectly through inhibiting GABA > increase dopamine release. Other neurotransmitter: serotonin (hallucinogenic effects). 9 Mechanisms of drug abuse Opiates Bind to an opiate-receptor on the presynaptic neuron >> inhibit GABA (GABA is inhibitory of dopamine) >> massive efflux of dopamine into the synaptic cleft. Mechanisms of drug abuse Benzodiazepines and barbiturates activate GABA-A receptors. However, they reduce GABA release that consequently disinhibit dopamine >> increase dopamine release. 11 Alcohol Also known as ethanol. Alcohol is the most commonly abused substance in modern society. Mechanism of action: enhancing the effects of the inhibitory neurotransmitter GABA. CNS depressant. Effects:…. At high doses > can result in coma and respiratory depression. Withdrawal symptoms: …… 12 13 Cocaine CNS stimulant Mechanism of action:… Cocaine has low oral bioavailability. Instead, the cocaine hydrochloride powder is snorted, or solubilized and injected. Crack cocaine can be smoked. Effects: euphoria, agitation, tachycardia, hypertension, respiratory failure, hyperthermia, chest pain, convulsion. 14 Amphetamines CNS stimulants Clinical effects and toxicity management are similar to cocaine. 15 Treatments of drug-related disorders 16 Treatments of drug-related disorders Treatment for substance use disorder includes: Treat intoxication: only if necessary (e.g., over-dose, symptomatic) usually by using antagonists (antidotes), this reverses the action of substances and can lead to precipitate of withdrawal symptoms. Treat withdrawal symptoms: usually by giving agonists (longer duration, milder withdrawal) with gradual discontinuation. Treat dependence: with aim of relapse prevention (by using anti craving). 17 Treatments of intoxication General principles in treating acute intoxications: Drug therapy should be avoided when possible (why?). Drug therapy may be indicated if patients are agitated, combative, or psychotic. Usually by parenteral (IV, IM) medications and for short-term (one or few doses). When toxicology screens are desired, blood or urine should be collected immediately upon arrival for treatment. 18 Treatments of intoxication Benzodiazepine overdose: Flumazenil Not indicated in all cases Risk of seizures Precipitate withdrawal Opiate intoxication: Naloxone Use to revive unconscious patients with respiratory depression Precipitate withdrawal 19 Treatments of intoxication Cocaine intoxication: Treat pharmacologically only if the patient is agitated or psychotic. Lorazepam can be used for agitation. Antipsychotics can be used for psychosis. Treat seizures supportively, but lorazepam or diazepam can be used for status epilepticus. Hallucinogen (e.g., marijuana): Reassurance. Antianxiety and/or antipsychotic 20 21 Treatment of withdrawal from drugs of abuse Alcohol: Standard of care for alcohol detoxification > symptom-triggered treatment with benzodiazepines (lorazepam is preferred). Drug can be administered parentally or orally. Address fluid, electrolyte, and vitamin deficiencies. Alcohol withdrawal seizures do not require anticonvulsant drug treatment unless they progress to status epilepticus. Patients with seizures should be treated supportively. 22 Treatment of withdrawal from drugs of abuse For benzodiazepine withdrawal, use the same drugs and dosages that are used for alcohol withdrawal (i.e. lorazepam) 23 Treatment of withdrawal from drugs of abuse Opiates: Conventional drug therapy for opiate withdrawal has bee methadone, a synthetic opiate. Usual starting doses have been 20 to 40 mg/day. The dosage can be tapered in decrements of 5 to 10 mg/day until discontinued. Some clinicians use discontinuation schedules over 30 days or over 180 days. 24 25 Treatments of substance use disorders The treatment of drug dependence or addiction is primarily behavioral. Treatment is a lifelong process. Aim to prevent relapses, usually by using anti-craving. Treatment of alcohol dependence and nicotine dependence. 26 Treatment of alcohol dependence Disulfiram, naltrexone, acamprosate, antidepressants, mood stabilizers. Disulfiram > deterrence, deters a patient from drinking by producing an aversive reaction if the patient drinks. Naltrexone, acamprosate, antidepressants, mood stabilizers> anti- craving. 27 Disulfiram It inhibits aldehyde dehydrogenase in the pathway for alcohol metabolism,… Inhibition of the enzyme continues for as long as 2 weeks after stopping disulfiram. Monitor liver function, used with extreme caution in patients with hepatic disorders. 28 Naltrexone Opioid antagonist. Reduces craving and the number of drinking days. It should not be given to patients currently dependent on opiates, as it can precipitate severe withdrawal syndrome. A depot formulation (intramuscularly) allows monthly administration. Hepatotoxic and contraindicated in patients with hepatitis or liver failure, require liver monitoring. 29 30 Treatment of nicotine First-line pharmacotherapies for smoking cessation are: Bupropion sustained release Nicotine Replacement Therapy (nicotine gum, nicotine inhaler, nicotine lozenge, nicotine nasal spray, nicotine patch) Varenicline Combinations of these should be considered if a single agent has failed. Second-line pharmacotherapies include nortriptyline and should be considered if first-line therapy fails. 31 Bupropion Antidepressant Bupropion sustained release (SR) is contraindicated in patients with a current or past seizure disorder, a current or prior diagnosis of anorexia nervosa, and use of a monoamine oxidase inhibitor within the last 14 days. Concurrent use of medications that lower the seizure threshold is a concern. 32 Varenicline Varenicline is a partial agonist that binds selectively to nicotinic acetylcholine receptors with a greater affinity than nicotine, producing a lesser response than nicotine. Prescribe for 12 weeks, and a second 12-week treatment can be given if the patient is not quit. It may result in a higher rate of cessation than bupropion. Side effects: behavioural adverse effects and cardiovascular events. 33 Questions 34 Thank you 35