Medicine – Antirheumatoid Drugs

1. Hydroxychloroquine

Hydroxychloroquine is a disease-modifying antirheumatic drug that helps reduce inflammation by altering immune activity. One of its actions is to interfere with complement-dependent antigen–antibody reactions, which decreases the inflammatory response involved in rheumatoid arthritis. Although it is generally considered less immunosuppressive than some other antirheumatic agents, long-term treatment requires careful monitoring. Important adverse effects include increased skin pigmentation, retinal maculopathy, and leukopenia. Retinal toxicity is particularly important because prolonged exposure may damage the macula and impair vision, so regular ophthalmological assessment is recommended during long-term therapy.

2. Gold

Gold compounds were previously used as disease-modifying drugs in rheumatoid arthritis, although they are now used much less frequently. Their antirheumatic effect is mainly related to the inhibition of macrophage activity, which reduces the release of inflammatory mediators and suppresses immune-mediated tissue damage. However, treatment with gold is associated with several significant adverse effects. The most common is dermatitis, which may occur in approximately 30% of patients. Renal complications such as proteinuria and glomerulonephritis can also develop. In addition, gold therapy may suppress bone marrow function and lead to thrombocytopenia, leukopenia, or, in severe cases, aplastic anaemia.

3. Penicillamine

Penicillamine is another older disease-modifying antirheumatic drug that works by altering immune responses. It can reduce circulating IgM rheumatoid factor and suppress T-cell activity, thereby decreasing some of the autoimmune processes involved in rheumatoid arthritis. Despite its therapeutic effects, penicillamine has a relatively wide range of adverse reactions. Patients may develop a maculopapular skin rash or loss of taste, particularly during treatment. Renal involvement may occur in the form of proteinuria or nephrotic syndrome. Penicillamine can also trigger autoimmune complications such as drug-induced lupus and myasthenia gravis. Haematological toxicity is another important concern, with possible thrombocytopenia and pancytopenia.

4. Sulfasalazine

Sulfasalazine is commonly used as a conventional disease-modifying antirheumatic drug. Its active systemic component, sulfapyridine, contributes to the suppression of inflammatory reactions and reduces the production of inflammatory mediators, including prostaglandins. Through these actions, the drug helps control joint inflammation and may slow disease progression. Gastrointestinal adverse effects such as nausea are relatively common, while skin rashes and hepatitis may also occur. Less common but important complications include pulmonary eosinophilia, haemolytic anaemia, and pancytopenia. In men, sulfasalazine may also cause a reversible reduction in sperm count, which usually improves after the medication is discontinued.

5. Methotrexate

Methotrexate is one of the most important disease-modifying antirheumatic drugs and is widely used in the management of rheumatoid arthritis. It acts as a folic acid antagonist and interferes with enzymes involved in folate metabolism, thereby reducing nucleotide synthesis and limiting DNA synthesis and cellular replication. At the lower doses used in rheumatoid arthritis, its major therapeutic effect is related to suppression of inflammatory and immune activity. Methotrexate can cause significant toxicity if not monitored properly. Important adverse effects include hepatotoxicity, which may progress to hepatic fibrosis with prolonged use, as well as bone marrow suppression and blood dyscrasias. Regular monitoring of liver function and blood cell counts is therefore important during treatment.

6. Cyclophosphamide

Cyclophosphamide is a powerful immunosuppressive and cytotoxic drug that may be used in severe autoimmune disease when stronger suppression of the immune system is required. It reduces both antibody-mediated and cell-mediated immune responses, thereby decreasing the activity of immune cells that contribute to inflammation and tissue injury. Because of its potency, the drug is associated with serious adverse effects. One characteristic complication is haemorrhagic cystitis, which results from toxic metabolites irritating the urinary bladder. Cyclophosphamide can also cause marked bone marrow suppression, leading to pancytopenia and an increased risk of infection, bleeding, and anaemia.

7. Azathioprine

Azathioprine is an immunosuppressive drug that acts mainly by inhibiting purine and nucleic acid synthesis. This action limits the proliferation of rapidly dividing immune cells, particularly lymphocytes, resulting in suppression of cell-mediated hypersensitivity and alteration of antibody production. By reducing immune-system activity, azathioprine can help control inflammatory and autoimmune disease. However, treatment may produce several important adverse effects. Bone marrow suppression can occur and may lead to reductions in white blood cells, red blood cells, and platelets. The drug may also cause cholestatic hepatitis, while gastrointestinal effects such as nausea and vomiting are relatively common. Another notable adverse effect is pancreatitis, which may require discontinuation of therapy.