Abortifacient Complications

Educational Objectives

The goal of this program is to improve management of toxicities associated with abortifacient substances. After hearing and assimilating this program, the clinician will be better able to:

1. Identify pharmaceutical agents and herbal supplements that may be used by patients seeking abortion.
2. Manage medication and supplement overdoses in pregnant patients.
3. Consider differences in bioavailability among administration routes when determining likelihood of fetal and maternal toxicity.

Summary

Pharmaceutical Agents

Mifepristone: the only Food and Drug Administration (FDA)-approved regimen in the United States (US) for induction of medical abortion; it is a progesterone antagonist that causes fetal detachment from the uterus; mifepristone is followed up with misoprostol after 24 to 48 hr to induce uterine contractions that induce separation of the embryo and preplacental tissue; use is regulated by a Risk Evaluation and Mitigation Strategy (REMS) program, in which the FDA provides several steps that must be followed by care providers and patients; providers must be credentialed and undergo training, and mifepristone can only be dispensed from specific pharmacies; recent change in the REMS program allows acquisition of mifepristone and misoprostol by mail, which has led to controversy in some states; toxicity of the FDA approved regimen is minimal, but it can interact with medications metabolized by cytochrome P450 3A4 (eg, aspirin, warfarin, calcium channel blockers); infection is a commonly reported adverse event, although it is unclear whether it is directly related to the medication regimen or to the abortion process itself; bleeding can occur, particularly with high doses of misoprostol

Antiandrogen medications: tamoxifen — an estrogen antagonist; its efficacy is questionable and may lead to excessive bleeding; using tamoxifen may be less effective because the effect of progesterone on pregnancy is greater compared with estrogen; aromatase inhibitors — prevent estrogen formation and have low toxicity; pregnancies have been reported while taking these medications; therefore, they are unlikely to be extremely effective at inducing abortion

Misoprostol: can be used alone to induce abortion with a low rate of adverse events during the first trimester; most adverse events are reported when used in the third trimester, especially in patients with a history of low transverse or classic caesarean section; there have been case reports of uterine tears with use during the second trimester (although the doses of misoprostol used in these cases are unknown), and occurrence in the second trimester is weakly associated with history of low transverse or classic caesarean section

Acetaminophen: the most common drug used by women attempting to induce abortion at home, likely because of easy availability; high doses can lead to liver toxicity, which requires administration of oral or intravenous (IV) N-acetylcysteine (NAC) for treatment; oral NAC is effective for treating acetaminophen toxicity and has hepatic first-pass metabolism; however, pregnant women are typically given IV NAC to avoid this hepatic first-pass metabolism because NAC can cross the placenta

Nonsteroidal anti-inflammatory drugs (NSAIDs): large doses of NSAIDs can result in premature closure of ductus arteriosus, potentially causing fetal hypoxia; ibuprofen and naproxen are derivatives of propionic acid and can cause profound metabolic acidosis when taken in high doses; metabolic acidosis may occur with 100 to 200 mg/kg doses of ibuprofen and 25 to 50 mg/kg of naproxen; supportive treatment, eg, IV fluids, can clear the acids; dialysis may be indicated (although rarely necessary); differentiating between causes of acidosis (eg, alcohol vs NSAID toxicity) can be challenging; if there is uncertainty, clinicians should perform tests to rule out ethylene glycol or methanol poisoning; turnaround time for detection of blood alcohol levels can be considerable

Aspirin-related compounds: concentration of methyl salicylate in oil of wintergreen is high, and ingesting 1 tsp of oil of wintergreen can be potentially toxic; consuming a large quantity of bismuth subsalicylate (Pepto Bismol) can cause aspirin toxicity; patients may not have symptoms initially, but metabolic acidosis can occur eventually; neem also has a substantial amount of salicylate; standard aspirin tests may not detect the presence of these substances and may yield falsely low results; discussion with patients to determine context is important for treatment; treatment includes urine alkalization and dialysis depending on severity; dialysis is necessary for acidemia that is not rapidly corrected with IV fluids and sodium bicarbonate

Iron overdose: commonly manifests as nausea and vomiting accompanied by acidemia; initially, FDA guidelines mandated all iron tablets to be sold in blister packs; however, the regulations changed after legal challenges from the drug industry; iron toxicities are not commonly observed; with iron toxicity, nausea and vomiting occur initially, improve, and then return when patients develop hepatitis; late presentations include hepatitis and gastric strictures; patients without substantial nausea and vomiting are unlikely to have iron toxicity

Methotrexate: used to terminate pregnancies; the dose regimen for ending pregnancy include intramuscular (IM) administration of 50 or 75 mg/m² in 1 to 2 doses; likelihood of treatment success for ectopic pregnancy is low if the mass in the tube is >3.5 cm or cardiac activity is visible; level of human chorionic gonadotrophin likely plays a role in effectiveness, but the levels at which methotrexate is likely to work are unclear; patients secretly attempting abortion are likely to use oral methotrexate; there have been anecdotal reports of women being denied methotrexate prescriptions for rheumatoid arthritis because of its possibility of use to end pregnancy; however, use of oral methotrexate to end pregnancy is difficult because it has low bioavailability and can cause extreme nausea; low-dose methotrexate taken over several days is more likely to cause toxicity than a single large dose; leucovorin is used to treat methotrexate toxicity; patient should be transferred to a center that has resources to measure methotrexate levels; glucarpidase cleaves intrathecal methotrexate and is used for overdose; however, timely acquisition is unlikely because the half-life of IM or IV methotrexate is ≈6 hr; methotrexate is associated with a very high risk for fetal deformity

Tretinoin (eg, Retin-A, Refissa, Renova): frequently available for treatment of acne in young women; spontaneous abortion has been reported with tretinoin; however, it is unclear if using tretinoin causes or increases the risk for spontaneous abortion; negative pregnancy test must be shown before receiving a prescription; report should be submitted to the FDA is the drug is dispensed to a pregnant woman

High-dose vitamin C: high-dose vitamin C with large quantities of alcohol appears online as a potential strategy to induce abortion; a high dose of vitamin C may increase the bioavailability of alcohol; high IV doses of vitamin C may result in acidemia; significant vitamin C-induced acidemia may cause hemolysis

Colchicine: used for gout; colchicine may cause diarrhea; speaker did not report any induction of abortion with colchicine; overdose of colchicine may cause extreme sickness with nausea and vomiting; colchicine overdose may be misdiagnosed as pancreatitis due to profound hemorrhagic gastritis with elevated pancreatic enzymes; patients may also develop permanent cardiopathy and neuropathy

Herbal Supplements

Deadly nightshade: also known as Atropa belladonna; term may be used to describe climbing nightshade; Atropa belladonna can cause significant antimuscarinic toxicity, whereas climbing nightshade may cause gastrointestinal upset; the term “emmenagogue” (induction of menstruation) may be used instead of “abortifacient” (induction of abortion)

Cohosh: available as black and blue cohosh; black cohosh has estrogen-like effects and is used to relieve menopausal symptoms; black cohosh may result in liver injury (eg, cholestatic jaundice) with an atypical pattern; Dietary Supplement Health and Education Act (DSHEA) prevents the FDA from regulating supplements unless the FDA proves that there is actual harm due to not following Good Manufacturing Practices (GMP); blue cohosh is similar to black cohosh but comes from blue-colored berries rather than yellow berries; blue cohosh is used to induce abortion due to its effects on uterine contraction; nicotinic toxicity has been reported with blue cohosh and may lead to muscle paralysis, respiratory paralysis, and seizures

Dong quai: a Chinese herb with an estrogen-like effect; limited literature is available to explain the mechanism of action; it is a potent CYP3A4 inhibitor, resulting in several drug-drug interactions; it affects the activity of calcium channel blockers and warfarin and may cause uterine contractions, but it has also been used to support pregnancy

Parsley: has minimal toxicity, and cervical relaxation may occur if used with other agents; parsley extracts are available that can be ground to make slushes and slurries for consumption; it may result in photodermatitis; parsley results in photochemical reactions that cause skin burn

Poison hemlock (Conium maculatum): a postsynaptic nicotine agonist that works similarly to succinylcholine; overdose may cause paralysis; treatments include airway control and supportive care

Cotton root bark: a progesterone antagonist and possesses oxytocic properties; highly available in the US

Worm killer (Aristolochia bracteolata): used as an anthelminthic agent; it contains aristolochic acid that may cause acute nephritis

Pennyroyal oil: has acetaminophen-like toxicity; NAC may be used; fomepizole (Antizol) may prevent apoptosis of liver cells and propagation of free radicals

Artemisia species: have a toxic effect profile; include Artemisia vulgaris (mugwort) and Artemisia absinthium (wormwood); wormwood contains thujone and camphor, both of which cause seizures; thujone also causes renal injuries

Thujone-containing plants: tansy — contains a high level of thujone; it is historically used to induce abortion; junipers — have a high level of thujone; tansy ragweed may be used instead and may cause hepatitis; rue — likely a progesterone blocker and has an effect similar to mifepristone; side effects include QT changes and significant nausea and vomiting

Plants containing cyanogenic glycosides: present in Manihot esculenta (also known as cassava or yuca), which should be detoxified before consumption; chronic use results in upper motor neuron disease; oral and intravaginal uses of yuca have been reported; cyanogenic glycosides are also present in African passionflower and Queen Anne lace; patients have nausea, vomiting, and persistent acidosis

Intravaginal applications: aconite — a sodium channel opener and prevents repolarization of the heart; foxglove — contains cardiac glycosides; Rangoon creeper — an AMPA agonist and causes degradation of dorsal gray matter, resulting in neurologic symptoms; abortion leaves — used in Tanzania; side effects include ulceration and bleeding; Abrus precatorius — inhibits synthesis of ribosomal proteins; Taxus species — contains taxanes that causes significant arrhythmias; pokeweed (Phytolacca americana) and rhododendrons — cause seizures and arrhythmias; Jimson weed and Mayapples — also known be toxic; Ricinus communis (castor) — may be used orally or intravaginally for abortion purposes; however, ricin toxicity can occur, and consuming castor beans can be extremely toxic; additionally, no specific treatment is available; castor beans are typically sold for nausea and vomiting rather than for abortion

Readings

Ascrizzi R, Fraternale D, Flamini G. Photochemical response of parsley (Petroselinum crispum (Mill.) Fuss) grown under red light: The effect on the essential oil composition and yield. J Photochem Photobiol B. 2018;185:185-191. doi:10.1016/j.jphotobiol.2018.06.006; Chen BA, Reeves MF, Creinin MD, et al. Misoprostol for treatment of early pregnancy failure in women with previous uterine surgery. Am J Obstet Gynecol. 2008;198(6):626.e1-626.e6265. doi:10.1016/j.ajog.2007.11.045; Gopinath H, Karthikeyan K. Neem in dermatology: Shedding light on the traditional panacea. Indian J Dermatol. 2021;66(6):706. doi:10.4103/ijd.ijd_562_21; Hunter LJ, Wood DM, Dargan PI. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID) overdose. Open Access Emerg Med. 2011;3:39-48. Published 2011 Jul 6. doi:10.2147/OAEM.S22795; Kaye J, Reeves R, Chaiten L. The mifepristone REMS: A needless and unlawful barrier to care. Contraception. 2021;104(1):12-15. doi:10.1016/j.contraception.2021.04.025; Licata A, Minissale MG, Stankevičiūtė S, et al. N-acetylcysteine for preventing acetaminophen-induced liver injury: a comprehensive review. Front Pharmacol. 2022;13:828565. Published 2022 Aug 10. doi:10.3389/fphar.2022.828565; Nayki U, Taner CE, Mizrak T, et al. Uterine rupture during second trimester abortion with misoprostol. Fetal Diagn Ther. 2005;20(5):469-471. doi:10.1159/000087115; Rao RB, Hoffman RS. Nicotinic toxicity from tincture of blue cohosh (Caulophyllum thalictroides) used as an abortifacient. Vet Hum Toxicol. 2002;44(4):221-222; Runde TJ, Nappe TM. Salicylates toxicity. [Updated 2022 Jul 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499879/; Stovall TG, Ling FW, Gray LA. Single-dose methotrexate for treatment of ectopic pregnancy. Obstet Gynecol. 1991;77(5):754-757.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Dolcourt’s lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Dolcourt was recorded at Michigan Emergency Medicine Assembly, held on August 1-3, 2022, on Mackinac Island, MI, and presented by University of Michigan Health. For information on future CME activities from this presenter, please visit https://medicine.umich.edu/. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

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Lecture ID:

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