Department of Child Health, University of Sriwijaya-Mohammad Hoesin Hospital, Palembang, Indonesia.
There are five cathegories of antiheumatic drugs: 1) Nonsteoridal Anti Inflammatory Drugs (NSAID); 2) Disease-Modifying Anti Rheumatic Drugs; 3) corticosteroids; 4) cytotoxic, immunosupresive and immunomodulatory agents; 5) biological response modifiers.1 These drugs often used in combination with each other as well as with other drugs such as anti hypertensive drugs, antibiotics, statins, and many more as pharmacological management of rheumatic disease. These drugs have known adverse reactions that could lead to morbidity even mortality to the patients.
In general, the occurrence of adverse drug reactions can be affected by 1) patient related factors such as extremes of age (neonates and elderly), maternity status, fetal development, creatinine clearance, allergy and body and fat distributions; 2) drug related factors such as polypharmacy (which is because of the patient suffer more than one disease); drug dosing and frequency; 3) social related factors such as race and ethnicity, smoking and alcohol drinking; and 4) disease related factors or accompanied disease.2
NSAIDs are among the five anti rheumatic drugs that commonly prescribed. They provide symptomatic antiimflammatory relief of pain and fever in children. A survey by Levy and Imundo among pediatric medical and surgical practitioners reported that at least 40% of the sample prescribed acetyl salycilic acid, ibuprofen, diclofenac, naproxen, indomethacin, celexocib and rofecoxcib. The survey also revealed that abdominal pain, easy bruising, epistaxis, gastric/duodenal ulcer, hypertension were the side effects reported by pediatric rheumatologists.3 Gastrointestinal symptoms can be minimized by ensuring that NSAIDs always given with food. GI complications prophylaxis using antacids and H2-receptor antagonist is controversial. Monitoring the blood pressure and reducing salt intake may reduce hypertension side effects. 1,4.
MTX is the most frequent DMARDS prescribed. Supplementation with folinic acid or folic acid during treatment with MTX may reduce GI side effect, hepatic dysfunction and discontinuation of MTX treatment. 5 Decreased appetite, nausea, vomiting, diarrhea, bloating and burning sensation in the retrosternal area are the most common side effect of antimalarial drugs. These adverse effects are more often when using chloroquine (10%) than hydroxychloroquine. Retinal toxicity is a concerning adverse effects of antimalarial. Evidence shows that retinal toxicity does not occur if the hydrochloroquine dose is maintained at less than 6.5 mg/kg ideal body weight/day. The risk of retinopathy is higher in chloroquine compared to hydoxychloroquine. Routine ophthalmology monitoring (every 6 months) to detect premaculopathy is recommended in patient using antimalarial drug.1,6
Glucocorticoids are the most potent antiinflamatory agent and widely used to treat patient with autoimmune disease. Gastritis, peptic ulcers, upper gastrointestinal bleeding can be minimized by administration of the oral glucocorticoid with food and the use of antacid medications, including H2 receptor antagonists or proton pump inhibitors. Sodium restriction may be required to prevent glucocorticoid induced hypertension. Frequent hand washing, avoiding exposure to infectious cases and use of appropriate vaccines could prevent patient with glucocorticoid therapy from being infected. Tuberculosis investigations should be done at prior to beginning therapy. Glucocorticoid therapy may disturb glucose metabolism and may lead to induction of diabetes.1,7 This adverse effect is increased with higher dose of glucocorticoid (prednisolone > 20 mg), longer duration of treatment, advanced age, high body mass index, previous glucose intolerance, previous glucocorticoid hyperglycemia, family history of diabetes mellitus and hemoglobin A1c
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2. Alomar MJ. Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J. 2013 Feb 24;22:83?94.
3. Levy DM, Imundo LF. Nonsteroidal Anti-Inflammatory Drugs: A survey of practices and concerns of pediatric medical and surgical specialists and a summary of available safety data. Pediatr Rheumatol [Internet]. 8(7). Available from: http://www.ped-rheum.com/content/8/1/7
4. Townsend RR. NSAIDs and acetaminophen: Effects on blood pressure and hypertension. Uptodate [Internet]. 2019 [cited 2019 Aug 10]. Available from: https://www.uptodate.com/contents/nsaids-and-acetaminophen-effects-on-blood-pressure-and-hypertension?csi=bce4b5b3-dfda-4f89-9c5d-de278c547ee8&source=contentShare
5. Shea B, Swinden MV, Ghogomu ET, Ortiz Z, Katchamart W, Rader T, Bomabardier C, Wells GA, Tugwell P. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. (5).
6. Haladyj E, Sikora M, Feliz-Giemza A, Olesinska M. Antimalarials ? are they effective and safe in rheumatic diseases? Reumatologia. 2018 May 9;56(3):164?173.
7. Aulakh R, Singh S. Strategies for Minimizing Corticosteroid Toxicity: A Review. Indian J Pediatr. 2008 Oct;75(10):1067?1073.
8. Suh S, Park MK. Glucocorticoid-Induced Diabetes Mellitus: An Important but Overlooked Problem. Endocrinol Metab [Internet]. 2017 Mar 27;32:180?189. Available from: www.e-enm.org
9. Guo Y, Tian X, Wang X, Xiao Z. Adverse effects of immunoglobulin Therapy. Front Immunol [Internet]. 2018 Jun 8;9(1299). Available from: www.frontiersin.org