Download
opioid dependence in pregnancy n.
Skip this Video
Loading SlideShow in 5 Seconds..
Opioid Dependence in Pregnancy PowerPoint Presentation
Download Presentation
Opioid Dependence in Pregnancy

Opioid Dependence in Pregnancy

295 Vues Download Presentation
Télécharger la présentation

Opioid Dependence in Pregnancy

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Opioid Dependence in Pregnancy James J. Nocon, M.D., J.D. Indiana University School of Medicine Chairman, Indiana Prenatal Substance Abuse Commission Director, Prenatal Recovery Clinic Wishard Memorial Hospital 1001 West 10th Street, F5102 Indianapolis, Indiana 46202 jnocon@iupui.edu October 7, 2011

  2. Objectives • Review Opioid Pharmacology • Types of Opioid Dependence • Managing Opioid Dependence • Prenatal • Intrapartum • Breast Feeding • Effects on the fetus and newborn • Withdrawal • Breast Feeding

  3. Pregnancy Enhances Recovery Pregnancy makes a difference in long-term recovery. After one year of treatment: 65.7% of women who entered treatment while pregnant used no drugs, while Only 27.7% of non-pregnant women remained drug free. (p<0.0005) Peles E, Adelson M. Gender Differences and Pregnant Women in a Methadone Maintenance Treatment (MMT) Clinic. J Addictive Diseases 2006; 25: 39-45. 3

  4. America Has Never Been Drug-freeMost commonly used drugs in order of frequency: • Cocaine –the 7% solution • Cannabis (THC) (2737 B.C China) • Laudanum– tincture of opium; • Morphine– from the Civil War • Methadone– developed in Nazi Germany prior to WWII • Alcohol –how the West was won • Amphetamine -1887; used extensively in WWII to keep soldiers alert; the US military uses with airmen today in Iraq • Methamphetamine -1893 • Methylenedioxy-methamphetamine (MDMA) Developed by Merck in 1912 as an appetite suppressant; today it’s called ecstasy 1800 to 2000 21st Century: 2002-2007 Cocaine 52 Cocaine and THC 59 THC 49 Methadone 42 Other Opiates27 Alcohol 10 Other Combinations 48 (opiates/amphetamines) Based on 287 pregnant patients treated from 2002 to 2007.

  5. What’s the Difference Between Opioids and Opiates? • Opiates • Alkaloids derived from the opium poppy • Morphine, Codeine, Thebaine • Opioids • All Opiates, plus: • Semi Synthetics – derived from the alkaloids (thebaine): hydrocodone; oxycodone; heroin • Synthetics: methadone; fentanyl; nubain; buprenorphine

  6. Changes In Opioid Use • Percent of pregnant patients dependent on opioids referred to an Indiana Substance Use Program: • 2002-2007: 69/287 patients: 24% • 2008: 69.3% • 2009: 79.1% • 2010: 75.5% • Includes heroin, opioid dependent chronic pain patients, opioid poly-substance users, methadone and buprenorphine maintenance.

  7. Opioid Abuse Skyrockets • Opioid prescription abuse is the fastest rising addiction and public health problem in the United States. • Over 2,000 deaths per week have been attributed to opioid abuse. • Most of the fatalities are due to Oxycontin • http://www.foodconsumer.org/newsite/Politics/32/opioid_abuse_skyrockets_061820100141.html

  8. What’s Oxycontin? • Oxycodone • Made by Perdue Pharma • Special coating allows for extended release • Marketed as safe – low addictive risk • Perdue Pharm sued for misbranding, among other issues. • East to remove the coating – rapid onset • Most abused Rx drug: • Especially in Kentucky and Tennessee: “Hillbilly Heroin” • OxyContin's warning label said to not crush the controlled-release tablets because of the potential for rapid release of oxycodone, which led many people to crushing the tablets and injecting or snorting the drug.

  9. Typical Doses of “Oxy” • 10 mg - white • 15 mg - grey • 20 mg - pink • 30 mg – brown – most often prescribed • 40 mg – yellow • 60 mg - red • 80 mg – greenish blue • Addicts typically use 250 mg/day to feel normal. • And 500-550 mg to get high. • It sells for about $1 per milligram

  10. PMP Restricts “Oxy” Abuse • 47 states have a Prescription Monitoring Program (PMP) • Inspect: http://www.in.gov/pla/inspect.htm • Florida’s program in jeopardy due to lack of state funding. • Lack of effective PMP allows “pill mills” to flourish as “Pain Clinics.” • 41 million prescriptions for Oxy in Florida (July to Dec 2010) • Only 4 million Rx for entire US.

  11. Political Ideology Enables “OXY” Abuse; Intent vs. Impact • Intent of Florida Governor • To reduce federal government and spending. • Rejects 15 million in Federal funds for the PMP. • Rejects the PMP because of opposition to supporting a “government database.” • Attempts to repeal Florida Law creating PMP • Impact: • Allows pill mills to flourish. • More “pain clinics” in Florida than McDonalds. • Kills 10 people per day in Florida • #1 drug of abuse among 12-17 year olds

  12. Others Enable “Oxy” Abuse • Organized Crime • Pharmacies • Doctors • Over $5,000 a day to write prescriptions in “pill mills” in Florida. • Can easily make over a million dollars/year • No nights, no call, just writer’s cramp. • And, America has never been drug free!

  13. What is Addiction? • Great question. Like obscenity, hard to define but, I know it when I see it. • Dependence • Psychological: withdrawal • Physical; tolerance and withdrawal • Addiction: continuing the behavior in spite of the adverse and illegal consequences of the behavior.

  14. Relationship View of Addiction • If the behavior keeps me from being physically and emotionally present for those I love and those who love me. • Then I have a problem with the behavior. • May be alcohol, tobacco or other drugs (ATOD) • May be eating, sex, gambling, etc. • Hoarding?

  15. Addiction in Women Late 19th Century: Women accounted for 2/3 of America’s opiate addicts and a large percentage of marijuana, sedative, cocaine and amphetamine addiction. Only 1 in 5 illegal drug addicts during 1914-1954 were women Approximate 15% of all pregnant women today are using alcohol, illegal and illicit drugs during pregnancy. Note: Americans constitute 4% of the world’s population and consume 2/3 of the entire drug supply.

  16. Psychiatric Gender Issues in Maternal Addiction • If sexually abused as a child: • 6 times more likely to become drug addict (opiates) • 4 times more likely to become an alcoholic • Kendler KS, et al. Childhood sexual abuse and adult psychiatric and substance use disorders; an epidemiological and co-twin control analysis. Arch Gen Psychiatry. 2000;57:953-959. • Major depression more frequent in women substance users. • Prescott et al. Sex specific genetic influences on the co-morbidity of alcoholism and major depression in a population-based sample of U.S. twins. Arch Gen Psychiatry. 2000;57:803-811.

  17. Other Women’s Issues in Addiction Alcoholic women usually have alcoholic spouses and less spousal support. (Holds true for opiates, as well) Redgrave, et al, Alcohol misuse by women. Int. Rev. Psychiatry 2003;15:256-268 Women more likely to abuse prescription drugs “My mother gave me her Xanax.” Vicodin, Lortab, Xanax and Klonopin. Bardel, et al. Reported current use of prescription drugs and some of its determinants among 35-65 year old women in mid-Sweden; a population based study. J Clin Epidemiol. 200 53;637-643

  18. The Pathophysiology of Addiction Just as alcohol, tobacco, and drugs activate the pleasure circuit in the brain, so do many behaviors such as sexual activity, winning a contest, gambling, and being praised. What drugs and behaviors have in common is the release of various neurotransmitters in nucleus accumbens in the brain: Dopamine – creates the “buzz.” Serotonin – sense of well being. Endorphins – euphoria. GABA (gamma amino butyric acid) – satiety and somnolence (sleepy after a big meal or sex) As repeated use of the drug or behavior depletes the dopamine, more activity is required to get the same effect. “Tolerance.” There comes a point when the affected person becomes an addict, as if a switch in the brain is flipped, and the person no longer has the ability to make free choices about the continued use of the drug. Leshner AI. Addiction is a brain disease, and it matters. Science 1997;278:45-47 18

  19. Pleasure in the Brainhttp://thebrain.mcgill.ca/flash/index_i.html • Ventral Tegmental Area • Nucleus Accumbens – dopamine rich center in the limbic area • Prefrontal Cortex – short term memory • Amygdala – moderates emotional influences on memory – fear response • MFB: medial forebrain bundle • These are the primary centers involved in pleasurable sensations. • Often referred to as “the Pleasure Circuit”

  20. Continuous Use of Drugs Changes Brain Cells • Dopamine System • Cocaine inhibits transporters • Amphetamine affects receptor and neurotransmitter release • Serotonin • Hallucinogens inhibit receptors • GABA/NMDA • Etoh inhibits and facilitates receptor function • Opiates have negative effect (Morphine; Heroin)

  21. Pathophysiology:Addiction Changes Brain Cells Addiction is a “double whammy.” • Tolerance - The brain needs more and more of the drug in order to get the same effect. And in this process, the brain cells are actually altered. • Drugs reduce fear response in Amygdala and Prefrontal cortex – person uses more drug with less fear of consequences. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA. Positron emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on brain serotonin neurons in human beings. Lancet 1998 Oct 31;352(9138):1433-7.

  22. You Know You Are Addicted • When you will do anything including breaking the law to obtain the drug, • Just to feel normal.

  23. An Important Digression: Alcohol and tobacco cause more fetal damage than all the other drugs combined including all the known teratogens.

  24. Strong Link Between Alcohol/Nicotine Use and Use of Illicit Drugs Among Women using BOTH Alcohol and Nicotine in the pregnancy • 20.4% used Marijuana • 9.5% used Cocaine Women NOT using Alcohol or Nicotine • 0.2% used Marijuana • 0.1% used Cocaine Alcohol and Nicotine use is also a marker for other drug use.

  25. Opiate Use In Pregnancy Derived from Poppy, PapaverSomniferum, 4000 BC • Morphine 1806 • Codeine 1832 • Heroin 1898 (Bayer) – was the drug of choice for obstetrical analgesia immediately post WWII • Methadone 1930 (Bayer) – synthetic opioid Other Commonly Used drugs • Marijuana noted in China 2737 BC – Major Cash crop in Jamestown 1611 • Cocaine - Spanish taxed it use 1569 • Amphetamine marketed by Smith Kline in 1887.

  26. Most Common Opiates Usedby Pregnant Patients • Hydrocodone: Vicodin; Lortab • Oxycodone: Oxycontin: Percocet • Methadone • Heroin • Opiates were mostly Category B Drugs • Animal studies appear to pose no risk, but • Definite risk established in humans • Visual defects confirmed in human studies with methadone.

  27. Maternal Treatment with Opioid Analgesics and Risk of Birth Defects • National Birth Defects Prevention Study, case-control study for infants born October 1, 1997, through December 31, 2005, in 10 states • Therapeutic opioid use was reported by 2.6% of 17,449 case mothers and 2.0% of 6701 control mothers. • Treatment was statistically significantly associated with: • conoventricular septal defects (OR, 2.7; 95% CI, 1.1–6.3 • atrioventricular septal defects (OR, 2.0; 95% CI, 1.2–3.6), • hypoplastic left heart syndrome (OR, 2.4; 95% CI, 1.4–4.1), • spina bifida (OR, 2.0; 95% CI, 1.3–3.2), or • gastroschisis (OR, 1.8; 95% CI, 1.1–2.9) in infants http://www.ajog.org/article/S0002-9378(10)02524-X/abstract

  28. Methadone: Visual Problems • Reduced acuity (95%), • Nystagmus (70%), • Delayed visual maturation (50%), • Strabismus (30%), • Refractive errors (30%), and • Cerebral visual impairment (25%). • Hamilton; Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy. Br J Ophthalmol doi:10.1136/bjo.2009.169284

  29. Opiate Pharmacology • Bind to receptors • Mu: analgesia; euphoria, respiratory depression, constipation, sedation, miosis • Kappa: dysphoria, sedation, psychotomimetic • Delta: unknown • Rate of Excretion faster than withdrawal • Morphine excreted within 72 hours • Methadone takes 4-5 days. • Clinical relevance is patient in withdrawal may have negative UDS. • Withdrawal in Adult: 6-24 hours from last dose • Morphine: 3-7 days duration • Methadone: 10-20 days or more

  30. Opiate Agonists • Morphine/Codeine/Dilaudid and Derivatives • Specificity for Mu receptor • Metabolized by liver • ½ life 2-4 hours • 90% excreted in urine/24 hrs • Methadone • 90% bound to protein • ½ life 20-40 hours • Slow release into blood

  31. Opiate Antagonists • Naloxone - Narcan • Very strong affinity for Mu receptor • Rapid competitive antagonist – 2-4 minutes • Lasts about 45 minutes • “Jump starts” withdrawal • Naltrexone - Vivitrol • Binds more slowly • ½ life 4 hours • Used in alcohol and opiate treatment.

  32. Opiate Agonist/Antagonists • Nalbuphine (Nubain) • 10 mg. IV or IM q. 3 hours ; onset 2-3 min IV • Neonatal half life: 4.1 hours • A favorite of OB nurses – less nausea • Butorphanol (Stadol) • 1-2 mg. IV or IM every 4 h; onset 1-2 min IV • Neonatal half life unknown • Buprenorphine (Subutex/Suboxone) • Long acting; long half life • Used for maintenance like methadone

  33. Pregnancy Increases Metabolism of Specific Opiates • Certain enzyme systems increases the metabolism of specific opiates, especially: • Methadone • Hydrocodone • Oxycodone • This is especially true of Methadone • Jarvis, M. A., S. Wu-Pong, et al. (1999). "Alterations in methadone metabolism during late pregnancy." J Addict Dis 18(4): 51-61.

  34. Increased Opioid Metabolism • Increases with each trimester, especially third • 30-40 percent of patients • Doses may increase by 50%. • May require more drug to treat pain • Methadone patient may be in chronic withdrawal by third trimester. • Higher does methadone actually has better outcome. • McCarthy, J. J., M. H. Leamon, et al. (2005). "High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes." Am J Obstet Gynecol 193(3 Pt 1): 606-610.

  35. Clinical Management of Opioid Dependence in Pregnancy • What is the Evidence? • Standard of Care • Opiate Overdose • Opiate Withdrawal • Opiate Maintenance • Chronic pain patients • Methadone maintenance • Buprenorphine maintenance • Opiate analgesia: labor; delivery; Cesarean • Neonatal Abstinence Syndrome (NAS) • Breastfeeding

  36. Opioid Use in PregnancyThis is the Evidence • 2002-2010 • Four Groups: 213 Patients • Pain patients using only opioids – 31 • Opiate dependent poly-substance patients – 45 • Methadone Maintenance - 90 • Buprenorphine Maintenance – 46 • Subutex – 12 • Suboxone - 34

  37. Opioid Dependent Chronic Pain Patients Using Opioids Only • Includes opioid/acetamenophen preparations. • N = 31 • Preterm Labor: 4 (12.9%) • Positive Meconium (other than opiates): none • Mean newborn weight: 3085.9 grams • LOS (newborn): 3.3 days; range 2-21 days • NAS treated: 1 • Intrapartum complications: 7 • No overdoses. • Nicotine use (> 0.5ppd): 21 (67.7%)

  38. Opioid Dependent Poly-substance Patients • Opioids plus cocaine, or THC or benzodiazepines or all three or more • N = 45 • Preterm Delivery: 8 (17.7%) • Positive Meconium (other than opiates): 12 (26.6%) • Mean newborn weight: 2879 grams • LOS (newborn): 7.8 days; range 2-89 days • NAS treated: 5 • Intrapartum complications: 7 • One antenatal overdose – mother and fetus survived • One fatal postpartum overdose • Nicotine Use (> 0.5ppd): 30 (66.6%)

  39. Opioid Only PatientsPostpartum Visit • Routinely at 4 weeks postpartum • N=31 • Did not return: 3 • Returned with positive UDS for drugs other than prescribed opioids: 5 • Returned “negative:” 23 (74.2%)

  40. Opioid Poly-substance PatientsPost Partum Visit • Routinely at 4 weeks postpartum • N=45 • Did not return: 13 (28.8%) • Returned with positive UDS for drugs other than prescribed opioids: 7 • Returned “negative:” 25 (55.5%)

  41. Comparison of Opioid and Opioid Plus Use in Pregnancy Opioid (31) Opioid + (45) p Preterm Delivery 4 (12.9 %) 8 (17.7%) NS Low Birth Weight (<2500g) 3 8 NS Mean Birth Weight 3085 g 2879g NS Positive Meconium 0 12 (26.6%) 0.001 NAS Treated 1 5 NS Mean Length of Stay 3.3 7.8 0.01 Failed to return PP 3 13 0.01 Returned PP “negative” 23 (74.2%) 25 (55.5%) NS

  42. Methadone Maintenance Patients • N = 90 (92 babies) • Preterm Delivery: 28 (30%) • Mean newborn weight: 2718g • LBW (< 2500g): 31/92 (33.7%) • Positive meconium: 9 (10.8%) • Mean LOS 30.3 days • NAS treated: 80 (86.9%) • Intrapartum Complications: 15 • Nicotine: 51/90 (56.6%)

  43. Methadone Maintenance Post Partum • Routinely at 4 weeks postpartum • N=90 (92 babies) • Did not return: 28 (31.1.%) • Returned with positive UDS for drugs other than prescribed opioids: 3 • Returned “negative:” 59 (65.5%)

  44. Buprenorphine Patients • Subutex N = 12; Suboxone N = 34; Total N= 46 • Preterm Delivery: 5 (10.9%) • Mean newborn weight: 3079.5 g • LBW (< 2500g): 5 (10.8%) • Positive meconium: 3 (6.9%) • Mean LOS: 6.78 days; range 2-49 days • NAS: 8 • NAS treated: 6 • Intrapartum Complications 8 • Nicotine: 29 (63%)

  45. Buprenorphine Postpartum • Routinely at 4 weeks postpartum • N=46 • Did not return: 13 (28.2%) • Returned with positive UDS for drugs other than prescribed opioids: 4 (8.6%) • Returned “negative:” 29 (63%)

  46. Methadone vs. Buprenorphine Major Pregnancy Outcomes Bup. (46) Meth (90) p Preterm Delivery 5 (10.9 %) 27 (30%) 0.001 Low Birth Weight (<2500g) 4 26 0.01 Mean Birth Weight 3079 g 2718g 0.005 Neonatal Abstinence (NAS) 8 89 0.001 NAS Treated 6 80 0.001 Mean Length of Stay 6.78 30.3 0.001 Failed to return PP 13 (28.8%) 28 (31.1%) NS Returned PP “negative” 29 (65.1%) 59 (65.5%) NS See also, Kakko J, Heilig M, Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug Alcohol Depend 2008 Jul 1;96(1-2):69-78.

  47. The Evidence Suggests NewTreatment Strategies • Prevention of Withdrawal • Opioid Overdose • Withdrawal • Detoxification • Maintenance • Methadone • Buprenorphine • Opioid dependent chronic pain patient • Polysubstance Use in Chronic Pain Patient

  48. Standard of Care:Prevention of Withdrawal • Evidence based literature clearly indicates that it is imperative to prevent opiate withdrawal in pregnancy: • Increased rate of preterm labor – 41% • Increased incidence of abruption 12% • Efforts to wean off or “detox” opiates in pregnancy carry an increased risk of harm to the fetus. • This represents a shift in the standard of care from “lowest possible dose” to “appropriate” doses to prevent withdrawal.

  49. Opiate Overdose • Characterized by pinpoint pupils, respiratory depression, coma, and pulmonary edema. • Establish airway. • Inject Naloxone – repeat if long acting opiate present, e.g., methadone. • Naloxone will not harm fetus. • Treatment will precipitate a severe withdrawal. • Will need to restart and modify an opioid dose • For maintenance, use methadone or buprenorphine • Methadone: start at 20 mg BID and increase 5-10 mg per day until stable. • Buprenorphine/naloxone: start at 2 – 4 mg BID; increase by 2-4 mg every 6 hours until withdrawal is abated

  50. Opiate Overdose Recovery • Will need to restart and modify opiate dose to prevent withdrawal. • Methadone maintenance – only by a federally certified clinic. • But a licensed physician may legally prescribe methadone to treat withdrawal in pregnancy for an inpatient. • Buprenorphine – only by a federally certified clinician.