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

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Presentation on theme: "Medical Complications of Drug Use Jeanette Tetrault, MD Assistant Professor of Medicine Yale University School of Medicine."— Presentation transcript:

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

6 Diagnoses of patients with occult major illness PatientDiagnosisBacteremia 1Infective EndocarditisGroup G β-hemolytic streptococcus 2Infective EndocarditisStaphylococcus aureus 3Infective EndocarditisStaphylococcus aureus 4Infective EndocarditisStaphylococcus aureus 5Infective EndocarditisStaphylococcus aureus 6Infective EndocarditisStaphylococcus aureus 7Infective EndocarditisStaphylococcus viridans 8PneumoniaNone 9PneumoniaNone 10Disseminated intravascular coagulation None 11Deep venous thrombosisNone

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 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 Heroin: A brief history

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


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

13 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

14 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

15 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

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

17 IDU chronic infectious complications: Viral Hepatitis B Hepatitis C HIV

18 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

19 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



22 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 Epidemiology of Hepatitis C (HCV)

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

24 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 Sexual Transmission of HCV

25 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

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

27 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

28 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

29 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 IDUs and Treatment of HCV

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

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

32 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 HIV/AIDS

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

34 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

35 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

36 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.

37 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.

38 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

39 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

40 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 Routine screening for patients with addiction

41 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

42 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

43 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

44 Thank you!

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