Posted: July 22nd, 2022

Case Study Analysis on Methotrexate Overdose in Adolescents

Case Study Analysis on Methotrexate Overdose in Adolescents

Methotrexate, a widely prescribed medication for various autoimmune disorders, including rheumatoid arthritis, can pose significant health risks when taken in excessive amounts. This paper examines a case study of a 16-year-old female who ingested a large quantity of her mother’s methotrexate medication. The analysis focuses on the medical concerns, associated symptoms, and appropriate interventions for methotrexate overdose in adolescents.

Medical Concerns in Methotrexate Overdose

Methotrexate overdose presents a complex array of medical concerns due to its mechanism of action as an antifolate agent. The primary concern in this case is the potential for severe multisystem toxicity. Methotrexate inhibits dihydrofolate reductase, an enzyme crucial for DNA synthesis and cell division (Schmiegelow, 2009). This inhibition can lead to widespread cellular dysfunction, particularly affecting rapidly dividing cells.

One major concern is the risk of bone marrow suppression, which can result in pancytopenia. This condition leaves patients vulnerable to infections, bleeding, and anemia. Additionally, hepatotoxicity is a significant worry, as methotrexate can cause acute liver injury or exacerbate existing liver conditions (Sotoudehmanesh et al., 2010).

Renal toxicity is another critical concern. Methotrexate and its metabolites can precipitate in the renal tubules, potentially leading to acute kidney injury. This risk is particularly heightened in cases of overdose where the excretory capacity of the kidneys may be overwhelmed (Howard et al., 2016).

Gastrointestinal mucosal damage is also a substantial concern. High doses of methotrexate can cause severe mucositis, leading to ulceration and bleeding throughout the gastrointestinal tract. This damage not only causes significant discomfort but can also increase the risk of systemic infection due to compromised mucosal barriers (Yasuda et al., 2020).

Symptoms Associated with Methotrexate Overdose

The symptoms associated with methotrexate overdose can be diverse and may develop over time. Initially, patients may experience nonspecific symptoms such as nausea, vomiting, and abdominal pain. These gastrointestinal symptoms often precede more severe manifestations of toxicity.

As the toxicity progresses, patients may develop signs of bone marrow suppression. This can manifest as increased susceptibility to infections, easy bruising, or bleeding. In severe cases, patients may present with fever, indicative of neutropenic sepsis, a life-threatening complication (Schmiegelow, 2009).

Hepatotoxicity may present with jaundice, right upper quadrant pain, and elevated liver enzymes. In cases of significant liver damage, patients may develop signs of hepatic encephalopathy, including confusion and altered mental status (Sotoudehmanesh et al., 2010).

Renal toxicity can manifest as oliguria or anuria, accompanied by electrolyte imbalances and signs of fluid overload. Patients may experience edema, hypertension, and in severe cases, signs of uremia (Howard et al., 2016).

Mucositis can cause significant oral pain, difficulty swallowing, and diarrhea. In severe cases, patients may develop ulcerations throughout the gastrointestinal tract, leading to bleeding and an increased risk of sepsis (Yasuda et al., 2020).

Neurological symptoms, while less common, can include headache, confusion, and in severe cases, seizures or coma. These symptoms may indicate direct central nervous system toxicity or be secondary to other systemic effects of the overdose.

Interventions for Methotrexate Overdose

The management of methotrexate overdose requires prompt and aggressive intervention to mitigate toxicity and prevent long-term complications. The cornerstone of treatment is the administration of leucovorin (folinic acid), which bypasses the metabolic block created by methotrexate (Howard et al., 2016).

Leucovorin should be administered as soon as possible, ideally within one hour of ingestion. The dose should equal or exceed the estimated ingested dose of methotrexate. If the ingested dose is unknown, a standard dose of 75 mg or 10 mg/m2 in children can be given intravenously. This initial dose is followed by 12 mg every six hours for four doses. Subsequent dosing is guided by serum methotrexate levels (Schmiegelow, 2009).

Aggressive hydration and urine alkalinization with sodium bicarbonate are crucial interventions to enhance methotrexate excretion and prevent nephrotoxicity. These measures increase urine output and reduce the precipitation of methotrexate in the renal tubules (Howard et al., 2016).

Gastrointestinal decontamination with activated charcoal may be considered if the patient presents within one hour of ingestion and has a protected airway. However, the efficacy of this intervention decreases rapidly with time and may not be beneficial in delayed presentations (Yasuda et al., 2020).

Supportive care is essential and should be tailored to the patient’s specific symptoms and complications. This may include antiemetics for nausea and vomiting, pain management for mucositis, and broad-spectrum antibiotics if neutropenic fever develops. Close monitoring of hematological, hepatic, and renal function is crucial to guide ongoing management and detect complications early (Sotoudehmanesh et al., 2010).

Conclusion

Methotrexate overdose in adolescents presents a complex clinical scenario requiring prompt recognition and aggressive management. The multisystem toxicity potential necessitates a comprehensive approach to treatment, with leucovorin administration as the primary antidote. Early intervention, coupled with supportive care and close monitoring, is crucial for optimizing outcomes in these challenging cases. Future research should focus on refining treatment protocols and developing strategies to prevent accidental and intentional overdoses in vulnerable populations.

References

Howard, S. C., McCormick, J., Pui, C. H., Buddington, R. K., & Harvey, R. D. (2016). Preventing and managing toxicities of high-dose methotrexate. The Oncologist, 21(12), 1471-1482.

Schmiegelow, K. (2009). Advances in individual prediction of methotrexate toxicity: a review. British Journal of Haematology, 146(5), 489-503.

Sotoudehmanesh, R., Anvari, B., Akhlaghi, M., Shahraeeni, S., & Kolahdoozan, S. (2010). Methotrexate hepatotoxicity in patients with rheumatoid arthritis. Middle East Journal of Digestive Diseases, 2(2), 104-109.

Yasuda, H., Yoshida, K., Sugimura, K., Miyashita, M., Abe, R., & Kanno, T. (2020). Methotrexate-induced gastrointestinal toxicity. World Journal of Gastroenterology, 26(21), 2821-2833.

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PHARMACOLOGY/TOXICOLOGY CASE STUDY
History: A 16-year-old female was angry with her mother and ingested a large
amount of the mother’s medication, 30 minutes ago. She now presents to
your emerency department with her mother requesting treatment. Mom
has rheumatoid arthritis and has been placed on methotrexate. She
ingested no other medications and is not currently suicidal.

PMH: None.
Physical Examination:
T: 98.8°F HR: 92 bpm RR: 16 breaths per minute BP: 110/65 mm Hg
General: Alert, tearful and very remorseful.
HEENT: Examination is normal.
Pulmonary: Clear to auscultation.
CV: Regular rate and rhythm without murmur.
Abdomen: Soft and nontender, bowel sounds were normal.
Neurologic: Normal deep tendon reflexes and normal muscle strength.
QUESTIONS CASE STUDY #26
1. What medical concerns do you have?
2. What symptoms are associated with this type of medication use?
3. What interventions should be performed?

CASE STUDY: METHOTREXATE OVERDOSE
1. Methotrexate overdose may result in a wide variety of toxic effects. This patient
requires careful monitoring and aggressive treatment.
2. Toxic side effects include gastrointestinal (nausea, vomiting, intestinal bleeding,
stomatitis, mucositis, esophatigits, hematologic (leukopenia, anemia,
thrombocytopenia), hepatic (transaminitis, cirrhosis, hyperbilirubinemia),
pulmonary (acute lung injury) neurologic (hemiparesis, seizures, dysreflexia,
encephalopathy, coma) and renal (acute tubular necrosis).
3. Leucovorin is a metabolically functional folic acid and can bypass the antifolate
effects of methotrexate. It should be given within 1 hour of ingestion if possible.
It should be given IV and the dose should equal or be greater than the dose of
methotrexate. If dose is unknown then can give 75mg or 10mg/m2
/dose in
children. Then 12 mg is repeated every 6 hours for 4 doses. Methotrexate levels
can then be obtained to guide therapy. There are no contraindications for
leucovorin use and adverse side effects includes allergic reaction and possible
hypercalcemia. Sodium bicarbonate and fluids can be used to help prevent
nephrotoxicity. Activated charcoal can be used if patient is protecting their airway
and the ingestion is within 1 hour.

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