The Wonderful DMARD with Multiple Toxicities

  • Yashika Kaushal
  • Ratibha Kausal
  • Isha Sharma
Keywords: Methotrexate, Adverse Drug Reactions, Toxicity, Patient Safety

Abstract

Methotrexate is a type of disease-modifying anti-rheumatic drug (DMARD). It is used to reduce activity of the immune system for people who have certain conditions. Methotrexate is a chemotherapy agent and immune system suppressant. Its use may be limited by concerns regarding its adverse reactions. The occurrence of adverse drug reactions in some cases leads to the therapy discontinuation. Although adverse drug reactions (ADR) of methotrexate generally do not pose a serious threat to the health of patients and a reduction in the dose of methotrexate leads to their elimination, in some cases severe toxicities of the drug occur unpredictably. These facts explain the need for close monitoring of the patient’s condition and the identification of potential risk factors for drug toxicity on the part of different organs and functional systems. The purpose of this review is to detail about safety and tolerability of methotrexate.

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Author Biographies

Yashika Kaushal

MBBS, Presently Clinical Observer, International Medical Graduate, Unit Number 322,  Building Number 8068,  120 A Street, Surrey,  British Columbia, Canada, Postal Code-V3W3P3

Ratibha Kausal

International Medical Graduate, British Columbia, Canada

Isha Sharma

Private Practitioner, Patiala

References

Edmudson W. Treatment of Psoriasis with Folic Acid Antagonists. Arch Dermatol. 1958;78(2):200.

Shen S, O’Brien T, Yap LM, et al. The use of methotrexate in dermatology: a review. Australas J Dermatol. 2012;53(1):1–18.

West J, Ogston S, Foerster J. Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials. PLoS One. 2016;11(5):e0153740. https://doi.org/10.1371/journal.pone.0153740

Van Ede A, Laan R, Blom H, et al. Methotrexate in rheumatoid arthritis: An update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum. 1998;27(5):277–92.

Bedoui Y, Guillot X, Sélambarom J, et al. Methotrexate an Old Drug with New Tricks. Int J Mol Sci. 2019;20(20):5023. https://doi.org/10.3390/ijms20205023

Conway R, Carey J. Risk of liver disease in methotrexate treated patients. World J Hepatol. 2017;9(26):1092. https://doi.org/10.4254/wjh.v9.i26.1092

Themido R, Loureiro M, Pecegueiro M, et al. Methotrexate hepatotoxicity in psoriatic patients submitted to long-term therapy. Acta Derm Venereol (Stockh).1992;72:361–4.

Kremer J, Galivan J, Streckfuss A, Kamen B. Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: Association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum. 1986;29(7):832–5.

Chan E, Montesinos M, Fernandez P, et al. Adenosine A2A receptors play a role in the pathogenesis of hepatic cirrhosis. Br J Pharmacol. 2006;148(8):1144–55. https://doi.org/10.1038/sj.bjp.0706812

Paul M, Hemshekhar M, Thushara R, et al. Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide. PLoS One. 2015;10(6):e0127558. https://doi.org/10.1371/journal.pone.0127558

Olsen E. The pharmacology of methotrexate. J Am Acad Dermatol. 1991;25(2):306–18.

Kim Y, Song M, Ryu J. Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway. Toxicology. 2009;256(3):183–90. https://doi.org/10.1016/j.tox.2008.11.016

Lateef O, Shakoor N, Balk R. Methotrexate pulmonary toxicity. Expert Opin Drug Saf. 2005;4(4):723–30. https://doi.org/10.1517/14740338.4.4.723

Ohbayashi M, Suzuki M, Yashiro Y, et al. Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro. J Toxicol Sci. 2010;35(5):653–61. https://doi.org/10.2131/jts.35.653

Grönroos M, Chen M, Jahnukainen T, Capitanio A, Aizman R, Celsi G. Methotrexate induces cell swelling and necrosis in renal tubular cells. Pediatr Blood Cancer. 2006;46(5):624–9. https://doi.org/10.1002/pbc.20471

Li X, Abe E, Yamakawa Y. Effect of Administration Duration of Low Dose Methotrexate on Development of Acute Kidney Injury in Rats. J Kidney. 2016;2(3):130. https://doi.org/10.4172/2472-1220.1000130

Cronstein B. The mechanism of action of methotrexate. Rheum Dis Clin North Am. 1997;23(4):739–55.

Genestier L, Paillot R, Fournel S, Ferraro C, et al. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102(2):322–8.

Lloyd M. The effects of methotrexate on pregnancy, fertility and lactation. QJM. 1999;92(10):551–63.

Buckley L, Bullaboy C, Leichtman L, Marquez M. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother. Arthritis Rheum. 1997;40(5):971–3.

Stern R, Laird N. The carcinogenic risk of treatments for severe psoriasis. Cancer. 1994;73(11):2759–64.

Kamel O, van de Rijn M, LeBrun D, et al. Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: Frequency of Epstein-Barr virus and other features associated with immunosuppression. Hum Pathol. 1994;25(7):638-43.

Kalantzis A, Marshman Z, Falconer D, et al. Oral effects of low-dose methotrexate treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(1):52–62. https://doi.org/10.1016/j.tripleo.2004.08.020.

Merrill J, Shen C, Schreibman D, et al. Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes. A mechanism for methotrexate-induced nodulosis in rheumatoid arthritis. Arthritis Rheum. 1997;40(7):1308–15.

Thakkar M, Engemann S, Walsh K, Sahota P. Adenosine and the homeostatic control of sleep: Effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience. 2008;153(4):875–80.

Quinn C, Griener J, Bottiglieri T, Hyland K, Farrow A, Kamen B. Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer. J Clin Oncol. 1997;15(8):2800–6.

Millot F, Dhondt J, Mazingue F, Mechinaud F, Ingrand P, Guilhot F. Changes of Cerebral Biopterin and Biogenic Amine Metabolism in Leukemic Children Receiving 5 g/m2 Intravenous Methotrexate. Pediatr Res. 1995;37(2):151–4.

May K, West S, Mcdermott M, Huffer W. The Effect of Low-Dose Methotrexate on Bone Metabolism and Histomorphometry in Rats. Arthritis Rheum. 1994;37(2):201–6.

CITATION
DOI: 10.26440/IHRJ/0507.10470
Published: 2021-10-30
How to Cite
1.
Yashika Kaushal, Ratibha Kausal, Isha Sharma. The Wonderful DMARD with Multiple Toxicities. IHRJ [Internet]. 2021Oct.30 [cited 2024Mar.28];5(7):RV5-RV10. Available from: https://ihrjournal.com/ihrj/article/view/470