Medical Consequences of Opiate Abuse

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Medical Consequences of Opiate Abuse
Jag Khalsa, Ph.D. Chief Medical Consequences
Branch, DPMC U.S. National Institute on Drug
Abuse NIH, USA Presented at II Latin American
Congress of Addictive Disorders Medellin,
Colombia July 25-28, 2007
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The National Institutes of Health
Center for Scientific Review
National Institute on Drug Abuse
National Cancer Institute
National Institute of Allergy and Infectious
Diseases
National Institute of Environmental Health
Sciences
National Eye Institute
National Institute of Arthritis and
Musculoskeletal Diseases
National Human Genome Research Institute
Center for Information Technology
National Institute of General Medical Sciences
National Institute of Mental Health
National Heart Lung and Blood Institute
National Center for Research Resources
National Institute of Child Health and Human
Development
National Library of Medicine
National Center for Complementary
and Alternative Medicine
Warren Grant Magnuson Clinical Center
National Institute on Aging
National Institute of Dental and
Craniofacial Research
National Institute of Neurological Disorders
and Stroke
National Institute on Alcohol Abuse and Alcoholism
National Institute of Diabetes and Digestive and
Kidney Diseases
John E. Fogarty Research Center
National Center on Minority Health and Health
Disparities
National Institute of Nursing Research
National Institute of Biomedical Imaging and
Bioengineering
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NIDA BUDGET
(Thousands)
2007Operating
2008P.B.
2005Actual
2006Actual
700,459 300,162 1,000,621
699,908 300,457 1,000,365
NonAIDS
693,282
698,976
AIDS
313,137
299,882
1,006,419
998,858
TOTAL
Increase Over Prior Year
1.2
-0.8
0.2
0.0
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NIDA
National Institute on Drug Abuse
Office of the Director
Nora D. Volkow, MD
Director
Director, AIDS Research
Special Populations Office
Timothy P. Condon, Ph.D.
Deputy Director
Laura S. Rosenthal
EEO
Associate Director for Management
Office of Extramural Affairs
Office of Planning Resource Management
Office of Science Policy Communications
Center for the Clinical Trials Network
Teresa Levitin, PhD
Laura Rosenthal
Timothy Condon, PhD
Betty Tai, PhD
Division of Clinical Neuroscience, Development
Behavioral Treatment
Division of Epidemiology, Services Prevention
Research
Division of Pharmacotherapies Medical
Consequences of Drug Abuse
Division of Basic Neurosciences Behavior
Research
Intramural Research Program
David Shurtleff, PhD
Frank Vocci, PhD
Wilson Compton, MD, MPE
Barry Hoffer, MD, PhD
Joseph Frascella, PhD
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Div Pharmacotherapies and Medical Consequences of
Drug Abuse

• Mission
• Develop medications to treat drug addiction
• Support national and international research on
  medical consequences of drug abuse and
  co-occurring infections including HIV, HCV, STDs,
  TB and others

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Medical Consequences Branch

• Substance Abuse 200-500 million
• 110 million life-time users, 19 million current
• Cost to the US society 534 billion/yr
• (Diabetes 132 b/yr Cancer 210 b/yr)
• Infections 500 million to 1 billion worldwide
• 300 Hepatitis B
• 170 Hepatitis C
• 40 million HIV
• Other bacterial infections

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Drugs

• Hallucinogens
• Inhalants
• Marijuana
• Nicotine
• Opiates
• Steroids
• Stimulants
• Amphetamines
• Cocaine

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Poppy
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Opiate Action in the Brain/CNS
Opiates can depress breathing by changing
neurochemical activity in the brain stem, where
automatic body functions are controlled.
Opiates can change the limbic system, which
controls emotions, to increase feelings of
pleasure. Opiates can block pain
messages transmitted through the spinal cord from
the body.
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Med Consequences contd.

• Opiates
• Heroin Use
• Route Inhalation, Injection, Smoking
• NSDUH (National Survey on Drug Use and Health)
• In 2005, 379,000 Americans 12 years of age or
  older used heroin in the past month
• 108,000 used it for the first time first use at
  age 22.5 year
• Other Rx Drugs (opiates, tranquilizers, sedatives
  for pain)
• In 2005, 25 million Americans 12 yr or older used
  these drugs
• 2.2 million were new drug users

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Med Consequences contd.

• Opiates
• Heroin Use
• MTF (Monitoring the Future)
• Annual prevalence of heroin in 8th, 10th and 12th
  grade students was less than 1
• Prevalence of other opiates in 2006
• Oxycontin 2.6, 3.8, and 4.3 in 8th, 10th, and
  12th grades, respectively.
• Vicodine 3.0, 7.0, and 9.7 in 8th, 10th, and
  12th grades, respectively.

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• Heroin/Oxycontin Use by Americans 12 year or
  older Numbers in thousands
• 2003 2004 2005
• Heroin-Life 3,744 (1.6) 3,145 (1.3) 3,534
  (1.5)
• Heroin-Yr 314 (0.1) 398 (0.2) 379(0.2)
• Heroin-Mo 119(0.1) 166 (0.1) 136(0.1)
• Oxycontin-Life2,832 (1.2) 3,072 (1.3) 3,481
  (1.4)
• Oxycontin-Yr---- 1,213 (0.5) 1,226 (0.8)
• Oxycontin-Mo---- 325 (0.1) 334 (0.1)
• NSDUH, SAMHSA, 2006

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Med Consequences contd.

• Opiates
• CNS
• Cardiovascular
• Respiratory/Pulmonary
• Renal
• Hormonal
• Musculoskeletal
• Immunological

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Opiate Action in the Brain/CNS
Opiates can depress breathing by changing
neurochemical activity in the brain stem, where
automatic body functions are controlled.
Opiates can change the limbic system, which
controls emotions, to increase feelings of
pleasure. Opiates can block pain
messages transmitted through the spinal cord from
the body.
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Med Consequences contd.

• Acute (Short-term) Effects
• Pleasurable sensation-Rush
• --Warm flushing of the skin
• --Dry mouthheavy feeling in extremities
• --Clouded mental functioning
• --Nausea, vomiting, severe itching,--
• --Slow cardiac function,
• --Depressed respiration to the point of death
  (overdose)
• --Spontaneous abortion

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Med Consequences contd.

• Chronic (long-term) Effects
• Most detrimentalAddiction (compulsive drug
  seeking,
• tolerance, physical dependence etc.)
• --withdrawal (restlessness, muscle and bone pain,
• Insomnia, diarrhea, vomiting, cold flashes with
  goose bumps cold turkey, leg movements
• Infectious diseases (HIV/AIDS, HCV, HBV)
• Bacterial Infections
• Abscesses and soft tissue infections
• Collapsed veins
• Infection of the heart lining and valves
• Arthritis and other rheumatologic complications

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Med Consequences contd.

• Cardiovascular
• Arrhythmias
• Cardiomyopathy
• Torsa de Pointes (polymorphic ventricular
  tachycardia)-Fatal
• QTc prolongation
• Cardiac arrest-heroin overdose
• Circulatory shock
• Vascular effects (collapsed veins)

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Med Consequences contd.

• Respiratory/Pulmonary Complications
• Pneumonia
• Tuberculosis
• Renal complications
• Acute renal failure,
• Nephropathy
• Glomerulopathy
• End-stage Renal Disease
• Musculoskeletal
• Rhabdomyolysis (very high levels of creatine
  kinase)

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Med Consequences contd.

• Immunological Consequences
• Effects on CD4 T cell lymphocytes
• Macrophages, Microglia
• Up-regulation of CCR5 and other receptors,
  inflammatory chemokines, leading to infectious
  disease progression
• Hormonal consequences
• HPGA- reduced testosterone and FSH levels
• Increased ACTH and Cortisol levels

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Med Consequences contd.

• Case report
• A 29-yr-old man, known to be a heroin addict,
  was found at home totally unrousable, bent on his
  hips in the lotus position. On admission, he
  required frequent ventricular defibrillation,
  external pacing and infusion of calcium. A
  diagnosis of rhabdomyolysis caused by heroin and
  cocaine overdose was made. He developed
  paraplegia below T12, acute renal failure, acute
  compartment syndrome in one leg and a coagulation
  defect. Despite a fasciotomy, a through-knee
  amputation of the leg was required. Haemodialysis
  was required for 26 days, and this period was
  complicated by increased serum calcium
  concentrations, which was treated with disodium
  pamindrate. Calcium deposits were palpable in the
  muscles and could be seen in vessels on limb
  x-rays. After 34 days, he was eventually
  discharged to a general surgical ward and
  subsequently into the community.

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Med Consequences contd.

• Case report
• A 29-year-old woman, addicted to heroin since
  the age of 15 years, presented with a 4-day
  history of acute inspiratory chest pain, dyspnoea
  and vomiting associated with hypoventilation. She
  died 3 h after admission to the intensive care
  unit inspite of active resuscitative measures.
  The main autopsy findings were limited to the
  heart, which showed widespread cardiac vein
  thrombosis, and both ventricles and the atria
  were associated with multiple areas of
  haemorrhagic myocardial necrosis.

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Med Consequences contd.

• Treatment of Opiate Addiction
• Detoxification
• Behavioral/pharmacotherapeutic
• Methadone
• Buprenorphine/Naloxone (Suboxone)
• Clonidine
• Lofexidine (alpha-agonist)
• Naloxone
• Naltrexone

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Med Consequences contd.

• Medical Consequences (Summary)
• CNS (addiction, physical dependence etc.)
• Cardiovascular Vascular effects (collapsed
  veins)
• Infections Bacterial infections of blood
  vessels, heart valves etc., abscesses and soft
  tissue infections
• Infections (HIV, HCV)
• Hepato-Renal Kidney and Liver diseases
• Respiratory/pulmonary Pneumonia and tuberculosis
• Musculoskeletal Arthritis and other
  rheumatologic problems

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Medical Consequences Branch

• Medical Consequences
• New PA/PAS/
• PA-07-007 Drug Abuse Aspects of HIV/AIDS
• Date January 2007  
• PAS-07-115 Non-injection Drug Abuse and HIV/AIDS
  (R01)
• Expiration Date January 3, 2009
• 3 million/yr
•  
• PAS-07-116 Health Disparities in HIV/AIDS Focus
  on African Americans (R01)
• Expiration Date January 2009
• 3 million/yr
•  
• PA-07-275 International Research Collaboration
  on Drug Addiction (R01)
• Expiration Date January 2009 (www.nida.nih.gov)

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CONTACT
Jag Khalsa, Ph.D. Chief Medical Consequences
Branch, DPMC National Institute on Drug
Abuse 6001 Executive Blvd., Room 4137, MSC
9551 Bethesda, MD 20892-9551 Telephone
301-443-2159 E-mail jk98p_at_nih.gov