current and novel treatment for substance abuse Flashcards
What are the Phases of substance use that are targets for pharmacotherapy
Can target any of these sections:
intoxication/overdose
withdrawal/detoxification
abstinence initiation/use reduction
relapse prevention
sequelae (psychosis, agitation, etc
Substance for which pharmacotherapy is available and not available
Available:
Opioids
Alcohol
Benzodiazepines
Tobacco (nicotine dependence)
Not available:
Cocaine
Methamphetamine
Hallucinogens
Cannabis
Solvents/Inhalants
List some pharmacological treatment strategies for substance abuse disorders
Agonist/partial agonist (replacement/substitution)
antagonist (blockade)
aversive (negative reinforcement)
correction of underlying/associated disorders (such as depression, etc.)
Dependence for treatment of opioid addiction
Lofexidine (non-substitute method of detoxification)
Central ⍺2-agonist, suppresses some components of withdrawal syndrome
Methadone (substitution method of detoxification)
Long-acting drug, no euphoria to morphine
Naltrexone, opioid antagonist, prevents euphoria to opioids
Given daily to addicts to prevent lapses
Buprenorphine (substitution method of detoxification)
Describe opioid dependence maintenance therapy
Methadone (must be administered through a registered narcotic treatment program)
Characteristics
Long acting mu agonist
Duration of action: 24-36 h
Dose: important issue and philosophical issue for many programs
30-40 mg will block withdrawal, but not craving
Illicit opiate use decreases with increasing methadone dose
80-100 mg is more effective at reducing opioid use than lower doses (e.g.: 40-50 mg/d)
Benefits: Lifestyle stabilization Improved health and nutritional status Decrease in criminal behavior Employment Decrease in injection drug use/shared needles
Naltrexone antagonist therapy for opioid addiction
Naltrexone Why antagonist therapy? Block effects of a dose of opiate Prevent impulsive use of drug Relapse rates high (90%) following detoxification with no medication treatment
Dose (oral): 50 mg daily, 100 mg every 2 days, 150 mg every third day
Blocks agonist effects
Side effects: hepatotoxicity, monitor liver function tests every 3 months
Biggest issue is lack of compliance; but those who “test” naltrexone by taking a dose of opioid and experiencing no effect do better with the medication
Injectable naltrexone not currently approved for opioid dependence, but likely to also be effective
How does buprenorphine work for opioid addiction
Partial MOPr/KOP antagonist Advantage/disadvantage over methadone? Lower risk of respiratory depression Lower retention rate Also used with Naloxone (Suboxone). Lower risk of withdrawal symptoms/lower craving for opioids
Treatment for alcohol dependence- general depressants
Treatment of alcohol dependence
Benzodiazepines (e.g. diazepam) effective against seizures
Clonidine, ⍺2-adrenoceptor agonist (inhibits excessive transmitter release)
Propranolol, β-blocker (blocks excessive sympathetic activity)
Acamprosate, weak NMDA antagonist (interferes with synaptic plasticity): reduced craving
Disulfiram, causes accumulation of acetaldehyde making alcohol consumption unpleasant
Naltrexone, opioid antagonist reduces alcohol-induced reward
Describe alcohol dependence pharmcotherapy
Two Phases of Alcohol Dependence:
1. Acute Alcohol Withdrawal
- Relapse Prevention: Maintenance Medications To Prevent Relapse To Alcohol Use (FDA approved)
Disulfiram
Naltrexone (oral and injectable)
Acamprosate
Note: monitor any patient being treated for a SUD for emergence of depression/anxiety/ suicidality as this can occur in the course of treatment
How tolerance and dependence to alcohol is caused
Tolerance and dependence
increased voltage-gated Ca2+ channels
decreased GABAA receptors
Marked abstinence syndrome, changes in Ca2+ channels lead to excessive neurotransmitter release
Tremor, nausea, sweating, fever, hallucinations
Seizures, confusion, agitation, aggression
Alcohol dependence (alcoholism) is common (4-5% of population)
Susceptibility to dependence, genetic factors
Linked to alcohol metabolism (alcohol dehydrogenase)
Benzodiazepines for acute withdrawal
Overdose:
Prolonged sleep without CVS or respiratory depression
Can become life threatening (respiratory depression etc.) with other CNS depressants e.g. alcohol
Reversed with flumazenil (competitive antagonist)
Tolerance & Dependence:
Tolerance – gradual escalation of dose needed to produce required effect (Q Any suggestions what might cause that?)
Dependence – stopping treatment causes marked in anxiety + tremor / dizziness, insomnia
What about benzodiazepines in alcoholics?
If your patient is alcoholic, try to avoid prescribing a BZD.
BZD produce cross-tolerance with alcohol
High risk of abuse of BZD
High risk of relapse to alcohol use
Combined use of alcohol and prescribed BZD can be very impairing and produce significant toxicity
If patient complains of anxiety:
1. consider use of serotonin reuptake inhibitors (this is first line treatment of anxiety disorders (not Benzos)),
2. refer to psychotherapeutic interventions (e.g.: cognitive-behavioral therapy),
3. consider relapse to alcohol
Describe disulfuram- alcohol relapse prevention meds
How it Works: Blocks alcohol metabolism leading to increase in blood acetaldehyde levels; aims to motivate individual not to drink because they know they will become ill if they do (Goodman and Gilman, 2001)
Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension
Contraindications: cardiac disease, esophageal varices, pregnancy, impulsivity, psychotic disorders, severe cardiovascular, respiratory, or renal disease, severe hepatic dysfunction: transaminases
Pharmacology of naltrexone
Similar structure to naloxone (Narcan)
Potent inhibitor of Mu opioid receptor binding
may explain reduction of relapse
because endogenous opioids involved in the reinforcing (pleasure) effects of alcohol
May explain reduced craving for alcohol
because endogenous opioids may be involved in craving alcohol
naltrexone for alcohol addiction:
doesn’t stop but reduces alcohol intake
Cochrane Review of NTX
decreased relapse to heavy drinking [RR = 0.64]
decreased return to any drinking [RR = 0.87 ]
NTX increased the time to first drink
NTX reduced craving
NTX was superior to acamprosate in reducing relapses, drinks and craving.
Describe nicotine dependence treatment
Nicotine dependence treatment
Nicotine replacement therapy
Relieves psychological and physiological withdrawal syndrome
Reduces cigarette consumption but not nicotine abstinence
Bupropion
Developed as antidepressant (blocks monoamine reuptake)
Nicotinic antagonist
May [DA] in nucleus accumbens
Can induce seizures, eating disorders and mania (bipolar disorder)
Varenicline (Champix)
Partial a4b2 nAChR agonist, full agonist for a7 nACHR
More effective than NRT
