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.
Contamination of the Opiate Supply with Fentanyl and Xylazine
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.
Much of the unregulated drug supply in the US has become contaminated by additives in recent years, also known as “cut”. Since 2016, contamination with fentanyl and its analogues, such as carfentanyl, has resulted in an increased risk of overdose (58). Fentanyl is a potent synthetic opioid and has similar pregnancy effects to other opioids. It can be injected, smoked, swallowed, or inhaled.
Contamination is not limited to opioids, but has also been reported in cocaine and methamphetamine.
There is no risk of overdose from touching fentanyl or being near it. Fentanyl does not absorb through the skin and does not aerosolize well, meaning that it is impossible to accidentally inhale enough to cause any effect. Reports of first responders overdosing in these ways are not substantiated by evidence and can be attributed to mental health crises. (64, 65)
Xylazine is another contaminant which is being found increasingly in drug supplies in the continental US (58). It is also known as Rompun, Anased, Sedazine, Chanazine, anestesia de caballo, el regalito, and el combito (62, 63). It has been identified as an adulterant in Puerto Rico for about 15 years (61, 63).
Xylazine is a veterinary sedative, and is not approved for human use. It can be injected, snorted, or swallowed (60). Its effects are reported to last about 4 hours (62). It belongs to the class of alpha-adrenergic medications, which cause sedation, low blood pressure, slowed heartbeat and breathing (60).
There are reports of Xylazine being used in cases of rape, homicide, and suicide (62). Xylazine causes physical dependence and withdrawal independently from opioids (60, 63). There is no published evidence about pregnancy and xylazine, but similar medications such as clonidine are used with caution in pregnancy and lactation due to concerns about heart rate and blood pressure changes in the pregnant person, fetus, and breastfed infant.
Xylazine can cause overdose death by itself, but is usually found in combination with other drugs such as heroin, fentanyl, and cocaine (60-63). Since xylazine is not an opioid, when it is present in a multi-substance overdose, naloxone (Narcan) may not be enough to reverse the overdose, but should still be given to reverse the effects of any opioids. Rescue breathing and supplemental oxygen are critical in responding to overdoses associated with xylazine. (58)
Xylazine is associated with increased risk of severe skin ulcers (aka: abscess). These ulcers are thought to be related to decreased blood flow to skin caused by xylazine. They may appear at injection sites or elsewhere on the body. These ulcers are far more severe than typical abscesses associated with injection drug use. There are reports of ulcers reaching the bone and causing bone thinning in healthy young people. (59-61, 63)
Many people who inject drugs can identify xylazine contamination by its appearance, smell, taste, and the way it makes users’ body fluids smell.
Some people report that it crystalizes after mixing and before injection. (60, 63) However, when researchers test used syringes, they find xylazine in many of the syringes of people who don’t think they’re using it and alternatively, they do not find it in all of the syringes of people who report that they are using it (61).
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).
Methadone and buprenorphine should be taken every day. Methadone is commonly available as a liquid or tablets, and buprenorphine is commonly available as tablets or dissolvable strips to be placed under the tongue.
Naltrexone (Vivitrol, Revia) is another medication that can be used for treatment of opioid use disorder (OUD). It is different from methadone and buprenorphine because it is an antagonist, rather than an agonist. Instead of activating the endorphin receptor, it blocks it. This means that opioids will not work until the naltrexone has worn off. Where methadone and buprenorphine can be thought of as a key that opens a lock, naltrexone can be thought of as shoving chewing gum into the lock. It is similar to the overdose reversal medication naloxone (Narcan), but takes longer to wear off.
Naltrexone can be taken as a daily or “as needed” tablet, or as a monthly injection called Vivitrol. With injected Vivitrol, it can take a month or more for the opioid blockade to wear off, and as it wears off, the person’s opioid tolerance gradually becomes lower and lower. Use of unprescribed opioids during this time is very dangerous because of risk of death by overdose (55-57).
There is no withdrawal in adults or infants, and overdose would require such large doses that it is practically impossible (53). There are no reports of any effect on infants exposed to naltrexone during pregnancy or lactation (47, 50-54). Roughly 1% of a parent’s dose is transferred into human milk (47, 56).
Naltrexone is less likely to be effective than agonist medications and comes with side effects including increased vulnerability to death by overdose (55-57). It requires a person to detox completely before the first dose to avoid severe precipitated withdrawal (53, 56). Some people with OUD find naltrexone to be helpful, but many others have a hard time sticking with treatment (56). Long-acting opioid blockers (such as Vivitrol) can be a problem for anesthesia and pain control during unexpected surgeries such as a C-section for premature labor, because many anesthesia medications are opioids (48, 49, 53, 56, 57).
Risk of overdose is increased for people who have been on naltrexone and then stop, or people who try to overcome the receptor blockade by taking massive amounts of opioids.
It is not recommended to start treatment with naltrexone during pregnancy (56). If a patient with OUD becomes pregnant before seeking treatment, agonist treatment should be offered as the gold standard, and naltrexone should only be available after a thorough risk/benefit discussion with a treatment provider familiar with pregnancy and OUD. (53) If someone who is stable on naltrexone becomes pregnant and desires to continue using the medication, it is considered safe to do so (53). Providers should work with pregnant patients to frequently re-assess satisfaction with treatment and evaluate whether a switch to an agonist medication would be beneficial.
The lack of infant withdrawal associated with naltrexone is a powerful influence on medication choice for patients. In addition, there are legal and child custody implications in many states for parents of an infant who experiences Neonatal Opioid Withdrawal (NOW), even if it is a result of taking OAT medication as prescribed. Nobody should ever have to make a healthcare choice under coercion. The care plan for every pregnant patient taking any Medication for Opioid Use Disorder (MOUD) requires inclusion of a thorough discussion of the local legal landscape and referrals to legal aid, if desired. Ethical providers work with patients to minimize the individual harm done by these laws and policies, and work to change such laws and policies where they exist.
These laws and policies are harmful to individual and public health and are opposed by the American Medical Association (AMA), the American College of Obstetricians and Gynecologists (ACOG), the Association of Women’s Health, Obstetric, and Neonatal Nurses (AWHONN), the American Society of Addiction Medicine (ASAM), and more. Full list can be accessed here Medical Groups Oppose prosecution (nationaladvocatesforpregnantwomen.org)
Whatever medication is chosen, the parent’s stable recovery is the most important factor influencing short- and long-term health outcomes for pregnancy and beyond.
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).
A Call for Social Justice That Encourages Breastfeeding
for Women Receiving Medication-Assisted Treatment for
Opioid Use Disorder
"Inequitable access to mother’s milk represents a social injustice with the potential to negatively impact the health and well-being of future generations... Lactation support providers can positively affect the health of societies through education, support, and participation in the development of policies and protocols that challenge current practice."
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 during pregnancy and while parenting (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).
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