PHARMACOLOGIC TREATMENT OF COMMON SUBSTANCE ABUSE DISORDERS LAUREN FISKE, MS4

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1 PHARMACOLOGIC TREATMENT OF COMMON SUBSTANCE ABUSE DISORDERS LAUREN FISKE, MS4

2 ACUTE ALCOHOL INTOXICATION Naloxone for patients in coma and/or with respiratory depression (empiric treatment for opioid poisoning) Rapid glucose blood testing if BAL> 50 mg/dl (may require dextrose administration) (Baum: 2014) Hemodialysis in patients with liver disease or with BAL >450 mg/dl (Osterhoudt KC, et al; 2006)

3 ALCOHOL WITHDRAWAL Shivanand K, et al (2013)

4 TREATMENT OF ALCOHOL WITHDRAWAL Rapid bedside glucose determination Dextrose infusion for hypoglycemia 100mg parenteral thiamine for prevention of Wernicke s encephalopathy Multivitamins supplemented with folate Shivanand K, et al (2013)

5 BENZODIAZEPINES FOR ALCOHOL WITHDRAWAL Benzodiazepines preferred medication for detoxification Stimulate GABA receptors by increasing frequency of GABA chloride channel opening decrease in neuronal activity Route: IV in patients with seizures or DTs Lorazepam 2-4mg IV q min Diazepam 5-10mg IV q 5-10 min Chlordiazepoxide (avoid in cirrhosis) Hoffman, et al (2014)

6 SYMPTOM TRIGGERED THERAPY VS FIXED SCHEDULED THERAPY Saitz, et al (1994): Symptom Triggered Therapy (STT) superior to Fixed Scheduled Therapy (FST) Saitz, et al (1994): Patients in STT group required less medication (median 100 vs 425mg clordiazepoxide) and shorter treatment period (median 9 vs 68 hours)

7 PHENOBARBITAL AND PROPOFOL FOR REFRACTORY DTS Refractory DTs: barbiturates, especially phenobarbital, in addition to benzodiazepines Phenobarbital increases duration of GABA chloride channel opening Phenobarbital mg IV q minutes Propofol: opens chloride channels in the absence of GABA (Hoffman, et al: 2014)

8 PHARMACOTHERAPY FOR ALCOHOL DEPENDENCE Disulfiram: Inhibits aldehyde dehydrogenase accumulation of acetaldehyde flushing, tachycardia, hyperventilation, nausea Induces conditioned avoidance response (Hoffman, et al: 2014)

9 PHARMACOTHERAPY FOR ALCOHOL DEPENDENCE Naltrexone: First line medication for alcohol use disorder Decreases alcohol consumption through Blockade of mu-opioid receptor and modification of HPA axis (Hoffman, et al: 2014) Roberts AJ et al (2000): mice lacking mu-opioid receptor do not self administer alcohol Rosner, et al; (2010): Naltrexone reduces risk of heavy drinking to 83% of risk in placebo group

10 PHARMACOTHERAPY FOR ALCOHOL DEPENDENCE Acamprosate Modulates glutamate neurotransmission at metabotropic glutamate receptors (Hoffman, et al: 2014) Rosner S et al (2010): acamprosate reduced rate of returning to drinking (RR 0.86, 95% CI) Should be used in conjunction with psychotherapy (Hoffman, et al: 2014)

11 TREATMENT OF CANNABIS INTOXICATION Rarely requires medical treatment Supportive treatment for anxiety, paranoia, palpitations Low dose benzodiazepine- lorazepam 0.5-1mg Antipsychotic- quetiapine 50 mg Teitelbaum, et al (2014)

12 TREATMENT OF CANNABIS USE DISORDER Psychosocial interventions preferred over medication Role for N-acetylcysteine? Gray, KM et al (2012): adolescents randomized to N-acetylcysteine group had twice the odds of having negative urine cannabinoid test than those assigned to placebo.

13 COCAINE INTOXICATION Benzodiazepine for cardiovascular symptoms Phentolamine for cocaine induced hypertension Diazepam for agitation (10mg IV followed by 5-10mg IV q 3-5 minutes until agitation is controlled) Teitelbaum, et al (2014)

14 COCAINE WITHDRAWAL No medication has been proven efficacious Lorazepam for sleep disturbance, severe agitation SSRI for depression/suicidal ideation > 2 weeks Teitelbaum et al (2014)

15 TREATMENT OF OPIOID OVERDOSE Naloxone: antagonist at μ, κ, and δ receptors (tenfold higher affinity for μ than κ) Reverses respiratory depression but not analgesia Saxon (2014)

16 TREATMENT OF OPIOID DEPENDENCE Antagonist: Naltrexone: longer duration of action than naloxone. Blocks effects of injected heroin for up to 48 hours. Krupitsky E, et al (2011): Naltrexone found to be more effective than placebo in treating opioid dependence in randomized trials. Hulse GK et al (2009): Long acting naltrexone (implant) preferred agent in patients who have difficulty adhering to daily dosing for opioid dependence.

17 MAINTENANCE THERAPY FOR OPIOID ADDICTION Methadone: long acting opioid agonist. Blocks opioid receptors, reducing euphoric effects of opioid abuse. Once daily dose of mg (Saxon, 2014) Desmond, DP et al (2000): Longitudinal, observational study showing 40% reduction in mortality in patients on methadone maintenance therapy compared to predicted mortality risk without methadone

18 MAINTENANCE THERAPY FOR OPIOID ADDICTION Buprenorphine: partial opioid agonist Available in combination with naloxone as 4mg buprenorphine/1mg naloxone given sublingually (Saxon, 2014) Mattick RP, et al (2008): Low dose methadone resulted in greater treatment retention than low dose buprenorphine Buprenorphine less likely to cause respiratory depression; typical dosing safe for opioidnaïve users. (Saxon, 2014)

19 PHARMACOTHERAPY FOR NICOTINE DEPENDENCE Nicotine replacement therapy (recommended duration 2-3 months) Nicotine gum or lozenge Nicotine inhaler Nicotine nasal spray Nicotine patch Rennard et al (2014)

20 PHARMACOTHERAPY FOR NICOTINE DEPENDENCE Bupropion: increases release of norepinephrine and dopamine by the CNS. Dosing: 150mg x3 days, then 150mg BID, starting 1 week before target quit date. Duration 7-12 weeks. (Rennard, et al 2014) Hughes JR, et al (2014): bupropion increases likelihood of smoking cessation compared with placebo (RR 1.62, 95%CI)

21 PHARMACOTHERAPY FOR NICOTINE DEPENDENCE Varenicline Partial agonist at alpha 4 beta-2 subunit of the nicotinic acetylcholine receptor. Dosing: 1mg daily x 12 weeks (Rennard et al, 2014) Jorenby DE, et al (2006): Varenicline superior to buprorpion in achieving four weeks of continuous abstinence during weeks 9-12 (44% varenicline vs 30% bupropion)

22 REFERENCES Baum, Carl: Ethanol intoxication in Children: Clinical features, evaluation, and management. UptoDate Shivanand K, Balaji B, et al. Clinical Management of Alcohol Withdrawal: A systematic review. In Psychiatry J Jul-Dec; 22(2): Hoffman, Robert and Weinhouse, Gerald: Management of moderate and severe alcohol withdrawal symptoms. Uptodate Osterhoudt KC, et al. Toxicologic emergencies. In: Textbook of Pediatric Emergency Medicine, 6 th, Fleisher GR, Ludwig S, Henretia FM. (Eds), Lippincott Williams & Wilkins, Philadelphia p 965 Saitz R, et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. Jama 1994; 272:519

23 REFERENCES Rosner S, Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2010; CD Rosner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010; CD Teitelbaum, Scott, Dupont, Robert, and Baily, John: Cannabis use disorder: Treatment, prognosis, and long-term medical effects. Uptodate Saxon, Andrew:. Treatment of opioid abuse and dependence. Uptodate Rennard, Stephen, Rigotti, Nancy, and Daughton, David. Pharmacotherapy for Smoking Cessation in Adults. Uptodate, 2014 Gray KM, Carpenter MJ, Baker NL, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry 2012; 169:805

24 REFERENCES Hulse GK, Morris N, Arnold-Reed D, Tait RJ. Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone. Arch Gen Psychiatry 2009; 66: 1108 Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomized trial. Lancet 2011; 377:1506 Desmond, DP, Maddux, JF. Deaths among heroin users in and out of methadone treatment. J Maint Addict 2000; 1:45 Mattick RP, Kimber J, Breen C, Daboli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2008; : CD Hughes JR, Stead LF, Hartmann-Boyce J, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2014; 1: CD Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006; 295:56

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