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Medical Complications of Drug Use

Medical Complications of Drug Use. Jeanette Tetrault, MD Assistant Professor of Medicine Yale University School of Medicine. Focus of today’s discussion. Complications of Injection Drug Use (IDU) Acute Withdrawal Bacterial infections: Skin, endovascular Chronic Hepatitis B Hepatitis C

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Medical Complications of Drug Use

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  1. Medical Complications of Drug Use Jeanette Tetrault, MD Assistant Professor of Medicine Yale University School of Medicine

  2. Focus of today’s discussion • Complications of Injection Drug Use (IDU) • Acute • Withdrawal • Bacterial infections: Skin, endovascular • Chronic • Hepatitis B • Hepatitis C • HIV • Prevention • Mortality and drug overdose

  3. Case: 31 yo man presents to ED feeling “sick” • 10 year history of injection heroin use • 6 month history of increasing cocaine use • Symptoms - myalgias, weakness, cough • No history of TB or HIV • PE – T 101.2, fresh and old track marks • No cardiac murmur, non-tender abdomen • Labs - WBC 12,000 with normal differential • Urine-trace protein

  4. Should the patient be hospitalized? • What clinical diagnoses are likely based on this presentation? • Which of these diagnoses merit hospitalization?

  5. Presentation of febrile IDUs Therefore, 36% (103) without apparent illiness • Of 296 febrile IDUs presenting to urban teaching hospital, 64% (180) had apparent major illness: 89% (92) with minor illness Cellulitis 37% Abscess 6% 11% (11) with major illness Endocarditis 6% Pneumonia 34% Samet JH, Shevitz A, Fowle J, Singer DE. Am J Med. 1990;89:53-57

  6. Diagnoses of patients with occult major illness

  7. Management of febrile IDUs • Significant univariate predictors of major illness • Fever (RR 4.76, 95% CI1.52-14.92) • Last IDU < 5 days PTA (RR 6.30, 85% CI 1.05-37.79) • Proteinuria (RR 4.44, 95% CI 1.27-15.5) • Recommendations for febrile IDUs • Decision to hospitalize rests on need for follow-up after blood cultures returned • If follow-up is not possible, patients should be hospitalized

  8. Case follow-up • Tests • Chest x-ray-normal • Blood cultures negative after 24 hours • Assessment/Plan • Diagnosis-Viral Syndrome • Patient discharged home • Referred for substance abuse counseling

  9. Heroin: A brief history • 1874-first synthesized by an English chemist • Diacetyl-morphine • 1897-resynthsized by Felix Hoffman working for Bayer trying to produce codeine • 1898-1910-marketed as a cough suppressant and non-addictive morphine substitute • Then discovered it was metabolized to morphine • 1914 Harrison Narcotics Act banned sale and distribution • 1924 became a Schedule 1 drug

  10. Injection drug use • Lifetime prevalence 1.33%(NSDUH, 2008) • 425,000 current IDUs • Medical complications of IDU result from: • Taking compound of uncertain composition • Solubilizing compound with a solvent (usually water) that has been sterilized to a widely-varying degree • Sterilizing the resulting mixture to a widely-varying degree • Violating the body’s most effective barrier vs. infection through use of needle • Injecting mixture directly into vasculature

  11. Acute complications: Opioid withdrawal • Severe flu-like symptoms • Anxiety • Hyperactivity • Drooling • Lacrimation/Tearing • Rhinorrhea/Runny nose • Anorexia • Nausea • Vomiting • Diarrhea • Myalgias • Muscle spasms

  12. IDU acute infectious complications: Soft tissue • Cellulitis, abscess, fasciitis: most likely reason for IDU hospital admission • Sites: any site of injection • Organisms: predominantly staph. and strep. • Antibiotics may fail due to local necrosis of vessels (especially in those who inject cocaine) • Drainage, often multiple times, may be required

  13. IDU acute infectious complications: Endocarditis • High risk of “right-sided” endocarditis • “left-sided” still more common • Usually skin flora • may be mouth flora from needle-licking • High degree of suspicion in febrile IDU (+/- heart murmur) • Blood cultures • Infection may be relatively benign or highly virulent • Treatment • Long term antibiotics • Surgery if valvular destruction, abcess or cerebral emboli Samet, Am J Med, 1996

  14. IDU acute infectious complications: Endovascular • Septic emboli • Small colonies of bacteria flick off vasculature (valves, vessels) into soft tissue/organ parenchyma • Metastatic seeding • Transient bacteremia from injection can settle in bone, muscle, joint space etc

  15. Harm reduction for IDUs • Use clean needles • Use sterile water as solvent • Rotate injection sites • Alcohol wipes on skin • Do not lick needles

  16. IDU chronic infectious complications: Viral • Hepatitis B • Hepatitis C • HIV

  17. Epidemiology of Hepatitis B • Estimated 1.25 million chronically infected in U.S. • Approximately 300,000 new cases per year • Transmission is blood borne, sexual, or perinatal • Approximately 50% of active injection drug users have serological evidence of prior exposure to HBV

  18. Natural history of Hepatitis B • Early disease manifests with symptoms of hepatic inflammation with elevated LFTs (> 10-20x normal) • Chronic viral hepatitis manifests as chronic liver disease with portal hypertension and poor hepatic synthetic function • Likelihood of developing chronic infection is related to age: • 80 to 90% of infants infected develop chronic disease • only 2 -10% of infected adults progress to chronic disease

  19. Epidemiology of Hepatitis C (HCV) • Most common blood-borne infection in the U.S. • Incidence: 35,000 new cases per year in U.S. • Seroprevalence studies reveal that approximately 1.8% of the U.S. population have been infected with HCV • IDU is the major risk factor for HCV • 65% of new cases • 20-50% of chronic infections • 40-90% of injection drug users (IDUs) have HCV antibodies National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002--June 10-12, 2002 Hepatology. 2002 Nov;36(5 Suppl 1):S3-20

  20. Natural history of HCV Acute HCV HCV Antibody + 10-20 years Chronic HCV 80% to 85% Resolved 15% to 20% Cirrhosis 10% to 15% Stable 85% to 90% Slowlyprogressive 75% HCC,liver failure 25% (2% to 4%) NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html.

  21. Sexual Transmission of HCV • Efficiency low • Rare, but not absent—estimated 0.03-0.6% per year between long-term monogamous discordant partners—no change in sexual practices recommended • Risk amongst those with multiple sexual partners is 1% per year—barrier methods or abstinence recommended • Presence of other sexually transmitted diseases increases risk of transmission

  22. Factors influencing progression of HCV • Virus • Viral Load • Genotype • Host • Sex • Age • Race • Duration of infection • Genetics • Immune response • Behaviors and Environment • Alcohol use • Drug use (licit and illicit) • HBV co-infection • HIV co-infection • Fatty liver infiltration • Iron overload

  23. Liver Function Tests in HCV 100 80 60 Patients* With HCV infection (%) 43 42 40 15 20 0 PersistentlyNormal ALT IntermittentlyElevated ALT Persistently Elevated ALT *Patients with ≥ 4 serum ALT level measurements during 25 months of follow-up (n = 1042). Inglesby TV, et al. Hepatology. 1999;29:590-596.

  24. Treatment milestones in HCV • RVR= rapid virologic response; week 4 • Absence of detectable HCV quantitative viral load • EVR= early virologic response; week 12 • cEVR=absence of detectable HCV quantitative viral load • pEVR=greater than 2 log (10) reduction in HCV viral load • EOTR=end of treatment response • Week 48 for genotype 1 and 4 infection or HIV-coinfection • Week 24 for genotype 2 and 3 infection • SVR=Sustained virologic response • Absence of detectable viral load 24 weeks after end of treatment

  25. Treatment of HCV: Pegylated IFN + Ribavirin • Goal of treatment=SVR • 42% for genotype 1 • 82% for genotypes 2 and 3 • Side effects • Pegylated interferon • Flu-like symptoms, depression, • 5-10% require discontinuation of therapy • Ribavirin • Pancytopenia, hemolytic anemia

  26. IDUs and Treatment of HCV • 2002 NIH guidelines on treatment of HCV • Management of HCV-infected IDUs is enhanced by linkage to drug treatment programs • Promotes collaboration between HCV experts and addiction medicine experts • HCV treatment of active IDU should be considered on a case-by-case basis • Active IDU should not exclude patients from HCV treatment

  27. Methadone treatment and HCV 100 P = .01 90 Controls (no IDU for ≥ 5 years) 76 80 P = .16 70 56 60 50 Patients on methadone maintenance Patients (%) 50 42 40 30 20 10 n = 50 50 50 50 0 ETR SVR Response Outcomes Mauss S, et al. Hepatology. 2004;40:120-124.

  28. Emerging therapies for HCV: Direct acting antivirals (DAA) Receptor bindingand endocytosis Transportand release Fusion and uncoating ER lumen Virionassembly (+) RNA LD LD LD Translation andpolyprotein processing Membranousweb RNA replication NS3/4 protease inhibitors NS5B polymerase inhibitors Nucleoside/nucleotide Nonnucleoside ER lumen Boceprevir Telaprevir NS5A* inhibitors *Role in HCV life cycle not well defined Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.

  29. HIV/AIDS • A blood-borne retroviral infection caused by the human immunodeficiency virus (HIV) • Transmission is through sexual contact, parenteral exposure, and perinatal or postpartum contact • 25% of the approximately 40,000 new HIV infections per year are through IDU • IDUs with HIV are less likely to receive antiretroviral treatment • IDUs less adherent to antiretroviral therapy, but addiction treatment found to increase medication adherence

  30. HIV/AIDS treatment • Standard is at least a three-drug regimen frequently called highly active antiretroviral therapy (HAART) • Medication classes: • Nucleoside reverse transcriptase inhibitors (e.g., Zidovudine or AZT) • Nucleotide reverse transcriptase inhibitors (e.g., Tenofovir or Viread) • Non-nucleoside reverse transcriptase inhibitors (e.g., Efavirenz or Sustiva) • Protease inhibitors (e.g., Indinavir or Crixivan) • Membrane fusion inhibitor (e.g., enfuvirtide or Fuzeon or T-20) • Newer Classes of medications (e.g., integrase inhibitors, CCR5 inhibitors)

  31. HIV seroconversion • Reduced by opioid agonist treatment among IDUs • Metzger, 1993: 2 cohorts of patients • 103 out-of-treatment intravenous opiate users • 152 subjects receiving methadone treatment HIV antibody conversion, 18-months • 22% of those out-of-treatment • 3.5% of those receiving methadone treatment Metzger DS, et al. Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18 month prospective follow up. JAIDS. 1993

  32. Methadone and HIV Prevention • Methadone patients report less needle and syringe sharing • Methadone patients are 3-6 times less likely to become HIV positive when compared to out-of-treatment heroin users, including the population who continues to use drugs De Castro S, Sabate E. Adherence to heroin dependence therapies and human immunodeficiency virus/acquired immunodeficiency syndrome infection rates among drug abusers.Clin Infect Dis. 2003 Dec 15;37 Suppl 5:S464-7

  33. Buprenorphine and HIV prevention • Buprenorphine is a partial opioid at the µ-opioid receptor, treatment option for opioid dependence • Longitudinal analysis of primary care patients on buprenorphine† • N=166 patients • Decreased risk behaviors between baseline and 24 weeks • IDU: 37% to 7%, p<0.001 • Sex while high: 64% to 15%, p<0.001 † Sullivan LE et al. Buprenorphine/naloxone treatment in primary care is associated with decreased HIV behaviors. JSAT. 35: 87-92. 2008.

  34. Buprenorphine and HIV treatment • MANIF cohort* • N=164 pts on HAART; 32 on bup, 113 prior IDU, 19 active IDU • Those on buprenorphine were more likely to be adherent to HAART than those with active IDU (OR 5.1 95%CI 1.3-20.1) • 6 mo follow-up no difference in CD4 and VRL between patients on bup and prior IDU • HIV+, opioid dependent patients treated with bup† • N=16 patients • + Utox 100% to 16% at 3 mos • No difference in HIV parameters *Moatti JP, et al. Adherence to HAART in French HIV-infected injecting drug users: the contribution of buprenorphine drug maintenance treatment. AIDS. 14(2) :151-5, 2000. † Sullivan, LE et al. A trial of integrated buprenorphine/naloxone and HIV clinical care. Clinical infectious diseases. 43 suppl:184-190, 2006.

  35. Methadone interactions with antiretrovirals • Nucleoside reverse transcriptase inhibitors • Methadone increases AZT through inhibition of glucoronidation • May increase side effects of AZT • Non-nucleoside reverse transcriptase inhibitors • Efavirenz decreases methadone levels • May cause withdrawal • Protease Inhibitors • No clinically significant interactions

  36. Buprenorphine interactions with antiretrovirals • Nucleoside reverse transcriptase inhibitors • No clinically significant interactions • Non-nucleoside reverse transcriptase inhibitors • Efavirenz decreases buprenorphine levels • Not clinically significant • Protease inhibitors (P450 3A4) • Atazanivir increases buprenorphine levels • May cause sedation

  37. Routine screening for patients with addiction • Viral Hepatitis A, B, C: Screening antibody tests and liver enzymes • HIV screening yearly • Tuberculosis: Annual screening with PPD and/or chest x-ray • Syphilis: Annual VDRL or RPR • Cervical cancer: Yearly screening PAP smear, more frequent (q6month) in those with prior abnormalities • Immunizations: pneumovax, flu, Tdap, twinrix

  38. Mortality as a result of drug overdose • Death from overdose is rare but may have spikes of increased incidence due to increased purity of illicit drugs • Particularly vulnerable times • Release from prison • Discharge from drug treatment • Respiratory depression is a factor BUT CNS depression is often the cause • Mixture of CNS depressants have additive effect; mixture of opioids/stimulants has complex interaction

  39. Other factors affecting mortality • Harder to quantify and usually ignored • Poor preventative care, uninsurance/underinsurance, fragmented healthcare • Poor health literacy • Poverty, malnutrition • Co-occuring and often poorly recognized/treated mental illness

  40. Summary • Patients with addiction frequently have co-morbid medical conditions, especially infectious diseases • Important to screen for these disorders, and to provide treatment and prevention interventions • Monitor patients for interactions between medications used to treat addiction and medications used to treat chronic diseases • Linkage of addiction treatment with medical treatments and prevention for co-morbid disorders can enhance medical treatment outcomes

  41. Thank you!

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