Opioids are central nervous system (CNS) depressants and the most commonly prescribed pain medications in the United States.
All opioids are chemically similar and typically have similar effects. They act on opioid receptors in both the spinal cord and brain to reduce the intensity of pain-signals.
Because opioids affect the parts of brain that regulate emotion, opioids are also very effective in reducing anxiety. And because they activate "reward" regions in the brain, they can create euphoria and get you "high."
Prescription opioid medications include - but are not limited to - hydrocodone (Vicodin®), oxycodone (OxyContin®, Percocet®), morphine, codeine, and fentanyl.
Some opioids, such as methadone and buprenorphine (Subutex®, Suboxone®) are used in the treatment of opioid use disorder (OUD) and are safe to use while pregnant or lactating. You may also see them called OAT, which stands for "Opioid Agonist Treatment."
Pharmacology is a branch of science that deals with the study of drugs and their actions on living systems - that is, the study of how drugs work in the body.
Opiates act by binding to the mu, kappa, and delta endorphin receptors.
The effects are pain relief, euphoria, respiratory depression, and cough suppression.
Acute side effects are itching, nausea, vomiting, dizziness, disorientation, somnolence, and pupil constriction.
Long term side effects are tolerance, dependence, and constipation (1).
Duration of action depends on individual factors and is specific to each medication.
Opiates are primarily metabolized in the liver, then excreted via urine, with a small percentage excreted via feces.
Opioid Agonist Treatment (OAT) is indicated as best practice for people with opioid dependence. Methadone or buprenorphine may be used (2), and higher doses are associated with decreased risk of relapse (3, 4).
Opiates, other than diamorphine (heroin), are placed by the FDA in pregnancy category C.
However, the World Health Organization (WHO) considers intravenous diamorphine (heroin) to be appropriate pain relief during labor (5).
There is some evidence of increased metabolic clearance of methadone and buprenorphine during pregnancy. This could mean that there is increased metabolic clearance of other opiates. The variation between individuals is considerable, with some pregnant people desirous of reducing their doses of methadone, but most people requiring increased doses as pregnancy progresses in order to avoid cravings and withdrawal, which can lead to relapse and overdose (2, 6-12).
Withdrawal during pregnancy is poorly understood, but is associated with adverse fetal and maternal outcomes.
Emerging evidence suggests that it may be possible to conduct gradual supervised detoxification in a hospital setting with reasonable obstetrical safety (13, 14).
Long term opioid agonist treatment (OAT) remains the gold standard of care, because it reduces negative effects on the pregnant person and fetus/newborn and alternatively, detoxification increases the risk of relapse and overdose death (13, 14).
Higher doses of methadone are not associated with increased length of stay for NOW treatment (15).
Opioid administration for opiate use in pregnancy has not been associated with congenital anomalies (2, 16, 17), except possibly for codeine, for which data is inconclusive (2).
Slightly increased rates of maternal and fetal mortality have been associated with opioid use, but no causal link has been established (18, 19).
Some studies find lower birthweights that are still within the normal range for gestational age (20-22), and some do not (15, 23).
Preterm labor and delivery less than 37 weeks gestation is sometimes found to be associated with prescribed and unprescribed chronic opiate use (19, 20, 22), but not always (15, 23).
Lack of adequate control for confounding variables in studies of this population causes difficulty in drawing conclusions, but it is probable that “maternal drug use is not the most important factor in how opiate-exposed infants and children develop.” (24).
Long term outcomes are similar to peer group, and services provided to pregnant people who use opioids should be similar to standard services (2, 24).
Opioids are transferred into human milk, with rates estimated at 1-3% of maternal dose for most opiates.
Because infant bioavailability in the gastrointestinal tract is poor, it is likely that infants actually absorb less than that. However, there are reports of mild infant sedation.
Long- or short-term prescription opiate use is not a contraindication to breastfeeding (25, 26). Because of individual differences in metabolism, codeine is not recommended while breastfeeding, due to risk of infant overdose (26).
Opioid overdose causes respiratory arrest (27).
Most overdose deaths involve more than one substance (28).
Risk of overdose increases after any period of abstinence, such as incarceration, hospitalization, leaving detox treatment programs or outpatient treatment, or trying to stop using (28).
If a person has experienced previous nonfatal overdose, their risk of nonfatal or fatal overdose increases (25, 29).
Opiate overdose is an emergency. Treatment includes rescue breathing and immediate administration of naloxone, repeating dose every 2 minutes until resuscitation or death. Chest compressions are not usually indicated because respiratory arrest, not cardiac arrest, is the problem (27).
Every patient at risk for opioid overdose should be offered take-home doses of injectable or intranasal naloxone with written instructions for storage and administration.
Avoid Dangerous Combinations
If you use these substances together you are at danger of overdosing or drug poisoning.
We care about your health and wellbeing. Please don't combine these substances.
NOTE: If you are using more than one of these medications at the same time you can work closely with your prescriber to maximize the positive therapeutic benefits of these drug combinations while being careful to minimize the risks of taking them together.
Signs and symptoms of opiate withdrawal can occur as soon as a few hours after the last dose.
Withdrawal can be induced immediately by administering naloxone or a partial agonist such as nalbuphine or buprenorphine.
Newborn infants should not be given naloxone if their mothers are known to have taken opioids regularly during pregnancy due to the risk precipitated withdrawal.
Withdrawal in the adult causes joint pain, sweating, nausea, vomiting, diarrhea, insomnia, anxiety, pupil dilation, tachycardia, runny nose, tremors, yawning, goose bumps (27), and has been implicated in death due to dehydration and electrolyte imbalance if left untreated (30-46).
1. Wolters Kluwer. (2010). Nursing 2010 drug handbook. Ambler, PA: Lippincott, Williams, and Wilkins.
2. Committee on Obstetric Practice (2017). Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstetrics and gynecology, 130(2), e81–e94. https://doi.org/10.1097/AOG.0000000000002235
3. Fareed, A., Vayalapalli, S., Casarella, J., & Drexler, K. (2012). Effect of buprenorphine dose on treatment outcome. Journal of addictive diseases, 31(1), 8–18. https://doi.org/10.1080/10550887.2011.642758
4. McCarthy, J. J., Leamon, M. H., Parr, M. S., & Anania, B. (2005). High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes. American journal of obstetrics and gynecology, 193(3 Pt 1), 606–610. https://doi.org/10.1016/j.ajog.2005.03.072
5. WHO recommendations: Intrapartum care for a positive childbirth experience. (2018). World Health Organization.
6. Shiu, J. R., & Ensom, M. H. (2012). Dosing and monitoring of methadone in pregnancy: literature review. The Canadian journal of hospital pharmacy, 65(5), 380–386. https://doi.org/10.4212/cjhp.v65i5.1176
7. Dickmann, L. J., & Isoherranen, N. (2013). Quantitative prediction of CYP2B6 induction by estradiol during pregnancy: potential explanation for increased methadone clearance during pregnancy. Drug metabolism and disposition: the biological fate of chemicals, 41(2), 270–274. https://doi.org/10.1124/dmd.112.047118
8. Wolff, K., Boys, A., Rostami-Hodjegan, A., Hay, A., & Raistrick, D. (2005). Changes to methadone clearance during pregnancy. European journal of clinical pharmacology, 61(10), 763–768. https://doi.org/10.1007/s00228-005-0035-5
9. Pace, C. A., Kaminetzky, L. B., Winter, M., Cheng, D. M., Saia, K., Samet, J. H., & Walley, A. Y. (2014). Postpartum changes in methadone maintenance dose. Journal of substance abuse treatment, 47(3), 229–232. https://doi.org/10.1016/j.jsat.2014.04.004
10. Wong, S., Ordean, A., Kahan, M., MATERNAL FETAL MEDICINE COMMITTEE, FAMILY PHYSICIANS ADVISORY COMMITTEE, MEDICO-LEGAL COMMITTEE, AD HOC REVIEWERS, & SPECIAL CONTRIBUTORS (2011). Substance use in pregnancy. Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 33(4), 367–384. https://doi.org/10.1016/S1701-2163(16)34855-1
11. Kashiwagi, M., Arlettaz, R., Lauper, U., Zimmermann, R., & Hebisch, G. (2005). Methadone maintenance program in a Swiss perinatal center: (I): Management and outcome of 89 pregnancies. Acta obstetricia et gynecologica Scandinavica, 84(2), 140–144. https://doi.org/10.1111/j.0001-6349.2005.00497.x
12. Hepburn, Mary. (2004). Substance abuse in pregnancy. Current Opinion in Obstetrics and Gynecology. 14. 10.1016/j.curobgyn.2004.07.006.
13. Bell, J., Towers, C. V., Hennessy, M. D., Heitzman, C., Smith, B., & Chattin, K. (2016). Detoxification from opiate drugs during pregnancy. American journal of obstetrics and gynecology, 215(3), 374.e1–374.e3746. https://doi.org/10.1016/j.ajog.2016.03.015
14. Dashe, J. S., Jackson, G. L., Olscher, D. A., Zane, E. H., & Wendel, G. D., Jr (1998). Opioid detoxification in pregnancy. Obstetrics and gynecology, 92(5), 854–858. https://doi.org/10.1016/s0029-7844(98)00312-3
15. Cleary, B. J., Eogan, M., O'Connell, M. P., Fahey, T., Gallagher, P. J., Clarke, T., White, M. J., McDermott, C., O'Sullivan, A., Carmody, D., Gleeson, J., & Murphy, D. J. (2012). Methadone and perinatal outcomes: a prospective cohort study. Addiction (Abingdon, England), 107(8), 1482–1492. https://doi.org/10.1111/j.1360-0443.2012.03844.x
16. Behnke, M., Smith, V. C., Committee on Substance Abuse, & Committee on Fetus and Newborn (2013). Prenatal substance abuse: short- and long-term effects on the exposed fetus. Pediatrics, 131(3), e1009–e1024. https://doi.org/10.1542/peds.2012-3931
17. Lind, J. N., Interrante, J. D., Ailes, E. C., Gilboa, S. M., Khan, S., Frey, M. T., Dawson, A. L., Honein, M. A., Dowling, N. F., Razzaghi, H., Creanga, A. A., & Broussard, C. S. (2017). Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review. Pediatrics, 139(6), e20164131. https://doi.org/10.1542/peds.2016-4131
18. Burns, L., Conroy, E., & Mattick, R. P. (2010). Infant mortality among women on a methadone program during pregnancy. Drug and alcohol review, 29(5), 551–556. https://doi.org/10.1111/j.1465-3362.2010.00176.x
19. Whiteman, V. E., Salemi, J. L., Mogos, M. F., Cain, M. A., Aliyu, M. H., & Salihu, H. M. (2014). Maternal opioid drug use during pregnancy and its impact on perinatal morbidity, mortality, and the costs of medical care in the United States. Journal of pregnancy, 2014, 906723. https://doi.org/10.1155/2014/906723
20. Bada, H. S., Das, A., Bauer, C. R., Shankaran, S., Lester, B. M., Gard, C. C., Wright, L. L., Lagasse, L., & Higgins, R. (2005). Low birth weight and preterm births: etiologic fraction attributable to prenatal drug exposure. Journal of perinatology : official journal of the California Perinatal Association, 25(10), 631–637. https://doi.org/10.1038/sj.jp.7211378
21. Hulse, G. K., Milne, E., English, D. R., & Holman, C. D. (1997). The relationship between maternal use of heroin and methadone and infant birth weight. Addiction (Abingdon, England), 92(11), 1571–1579.
22. Cleary, B. J., Donnelly, J. M., Strawbridge, J. D., Gallagher, P. J., Fahey, T., White, M. J., & Murphy, D. J. (2011). Methadone and perinatal outcomes: a retrospective cohort study. American journal of obstetrics and gynecology, 204(2), 139.e1–139.e1399. https://doi.org/10.1016/j.ajog.2010.10.004
23. Wurst, K. E., Zedler, B. K., Joyce, A. R., Sasinowski, M., & Murrelle, E. L. (2016). A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings. Substance abuse : research and treatment, 10, 89–97. https://doi.org/10.4137/SART.S38887
24. Center for Substance Abuse Treatment. (2005). Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Substance Abuse and Mental Health Services Administration (US).
25. Darke, S., Williamson, A., Ross, J., Mills, K. L., Havard, A., & Teesson, M. (2007). Patterns of nonfatal heroin overdose over a 3-year period: findings from the Australian treatment outcome study. Journal of urban health : bulletin of the New York Academy of Medicine, 84(2), 283–291. https://doi.org/10.1007/s11524-006-9156-0
26. National Institute of Health US National Library of Medicine TOXNET (2018). LactMed Database. Retrieved from: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~ViU0iT:1
27. Fareed, A., Stout, S., Casarella, J., Vayalapalli, S., Cox, J., & Drexler, K. (2011). Illicit opioid intoxication: diagnosis and treatment. Substance abuse : research and treatment, 5, 17–25. https://doi.org/10.4137/SART.S7090
28. Martins, S. S., Sampson, L., Cerdá, M., & Galea, S. (2015). Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature. American journal of public health, 105(11), e29–e49. https://doi.org/10.2105/AJPH.2015.302843
29. Gjersing, L. et al. (2017). Emergency service use is common in the year before death among drug users who die from an overdose. Journal of substance use. 22(3). 331-336.
30. Darke, S., Larney, S., & Farrell, M. (2017). Yes, people can die from opiate withdrawal. Addiction (Abingdon, England), 112(2), 199–200. https://doi.org/10.1111/add.13512
31. Fiscella, K., Pless, N., Meldrum, S., & Fiscella, P. (2004). Alcohol and opiate withdrawal in US jails. American journal of public health, 94(9), 1522–1524. https://doi.org/10.2105/ajph.94.9.1522
32. Miller, Michael E. A heroin addict begged his jailers for an IV. They Refused. Six hours later, he dies of dehydration. Washington Post. October 15, 2015.
33. Patrick, Robert. St. Louis settles lawsuit over inmate's heroin withdrawal death. St. Louis Post-Dispatch. February 28, 2014.
34. Woolington, Rebecca. Dying alone: A jail inmate's health spiraled for 7 days and no one stopped it. The Oregonian. April 10, 2016.
35. Hollander, Zaz. She died in the Anchorage jail detoxing from heroin. Her family wants answers. Anchorage Daily News. April 9, 2016.
36. Stewart, Les. Tori Herr's mother sues county over death. Lebanon Daily News. July 11, 2016.
37. Lopez, German. David Stojcevski's horrifying death in jail, explained. Vox. September 29, 2015.
38. Bay City News. Woman in custody at Santa Cruz county jail dies of 'natural causes,' opiate withdrawal, heroin abuse: coroner. NBC Bay Area January 2, 2016.
39. Nevada jail death: guards disobeyed department policies, documents show. CBS This Morning. September 5, 2018.
40. Sofield, Tom. Lower Bucks County man died in prison of drug withdrawal. Newton PA Now March 17, 2018.
41. Ray, Karla. Inmates' deaths prompts Lake County to demand action plan from jail's medical facility. WFTV9. August 10, 2018.
42. Vielmetti, Bruce. Family sues over woman's death in Milwaukee County jail. Journal Sentinel. June 1, 2018.
43. Anderson, Taylor W. 'I'll bet it feels like you're going to die, doesn't it?' Salt Lake County jailers thought inmate was withdrawing from heroin before her 2016 death, family says. The Salt Lake Tribune. March 22, 2018.
44. Rickert, Aprille. Tentative settlement reached in lawsuit over Floyd County jail inmate death. News and Tribune. July 19, 2018.
45. Anderson, Taylor W. Records indicate inmate begged for help before dying in Duchesne County jail. The Salt Lake Tribune. April 28, 2017.
46. Burns, Gus. Lawsuit says jailers to blame in woman's death behind bars. MLive. July 17, 2018.