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

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
• HIV
– Prevention
– Mortality and drug overdose
Case: 31 yo man presents to ED feeling “sick”
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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
Should the patient be hospitalized?
• What clinical diagnoses are likely based on this
presentation?
• Which of these diagnoses merit hospitalization?
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
89% (92) with
minor illness
Abscess 6%
Cellulitis
37%
Endocarditis 6%
Pneumonia
34%
Samet JH, Shevitz A, Fowle J, Singer DE. Am J Med. 1990;89:53-57
11% (11) with
major illness
Diagnoses of patients with occult major illness
Patient
Diagnosis
Bacteremia
1
Infective Endocarditis
Group G β-hemolytic
streptococcus
2
Infective Endocarditis
Staphylococcus aureus
3
Infective Endocarditis
Staphylococcus aureus
4
Infective Endocarditis
Staphylococcus aureus
5
Infective Endocarditis
Staphylococcus aureus
6
Infective Endocarditis
Staphylococcus aureus
7
Infective Endocarditis
Staphylococcus viridans
8
Pneumonia
None
9
Pneumonia
None
10
Disseminated intravascular
coagulation
None
11
Deep venous thrombosis
None
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
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
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
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
Acute complications: Opioid withdrawal
• Severe flu-like symptoms
• Anxiety
• Hyperactivity
• Drooling
• Lacrimation/Tearing
• Rhinorrhea/Runny nose
• Anorexia
• Nausea
• Vomiting
• Diarrhea
• Myalgias
• Muscle spasms
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
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
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
Harm reduction for IDUs
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Use clean needles
Use sterile water as solvent
Rotate injection sites
Alcohol wipes on skin
Do not lick needles
IDU chronic infectious complications: Viral
• Hepatitis B
• Hepatitis C
• HIV
Epidemiology of Hepatitis B
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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
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
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
Natural history of HCV
Acute HCV
HCV Antibody +
10-20 years
Resolved
15% to 20%
Chronic HCV
80% to 85%
Stable
85% to 90%
Cirrhosis
10% to 15%
Slowly
progressive
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.
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
Factors influencing progression of HCV
• Virus
• Behaviors and Environment
– Viral Load
– Alcohol use
– Genotype
– Drug use (licit and illicit)
• Host
– HBV co-infection
– Sex
– HIV co-infection
– Age
– Fatty liver infiltration
– Race
– Iron overload
– Duration of infection
– Genetics
– Immune response
Patients* With HCV infection (%)
Liver Function Tests in HCV
100
80
60
42
43
40
15
20
0
Persistently
Normal ALT
Intermittently
Elevated 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.
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
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
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
Patients (%)
Methadone treatment and HCV
100
90
80
70
60
50
40
30
20
10
0
P = .01
76
P = .16
50
56
42
n=
50
50
50
ETR
SVR
Response Outcomes
Mauss S, et al. Hepatology. 2004;40:120-124.
50
Controls (no
IDU for ≥ 5
years)
Patients on
methadone
maintenance
Emerging therapies for HCV: Direct acting
antivirals (DAA)
Receptor binding
and endocytosis
Transport
and release
Fusion
and
uncoating
ER lumen
(+) RNA
LD
LD
Translation
NS3/4 and
protease
polyprotein
inhibitors
processing
Boceprevir
Telaprevir
Virion
assembly
LD
Membranous
web
ER lumen
NS5A* inhibitors
*Role in HCV life cycle not well defined
Adapted from Manns MP, et al. Nat Rev Drug Discov. 2007;6:991-1000.
NS5B polymerase
RNA
replication
inhibitors
Nucleoside/nucleotide
Nonnucleoside
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
HIV/AIDS treatment
• 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 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
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
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.
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.
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
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
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 xray
• Syphilis: Annual VDRL or RPR
• Cervical cancer: Yearly screening PAP smear, more
frequent (q6month) in those with prior abnormalities
• Immunizations: pneumovax, flu, Tdap, twinrix
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
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
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
Thank you!