1. Cause of disability. Changes in the joint inflammation, proliferation of the synovium, errosion of cartilage & bones.

2. 1 in every 100 people suffer from rheumatoid arthritis. 3:1 female preponderance.

5. Drugs with different chemical structure & mechanism of action. DMARDs improve symptoms &↓ disease reactivity. Measurment of improvement

7. A folic acid antagonist with cytotoxic & immunosuppressive activity. It is a first choice DMARD. It is active in this condition at much lower doses than those needed in cancer chemotherapy. Mechanism of action.

8. 70% absorbed after oral administration. t½= 6–9 hours. Methotrexate's concentration is increased in the presence of hydroxychloroquine.

9. A potent anti rheumatoid drug, with a more rapid onset of action than other DMARD & less adverse effects. ADR:- pulmonary fibrosis, progressive dose-related hepatotoxicity. It is contraindicated in pregnancy.

10. Rheumatoid arthritis, chronic inflammatory bowel disease. It is split into its components [sulphapyridine & 5- aminosalicylic acid ] by bacteria in the colon.

11. ↓ IgA and IgM rheumatoid factor production are decreased. ½ T cell responses to concanavalin ↓ B cell proliferation. Only 10–20% of orally administered sulfasalazine is absorbed.

12. Sulfapyridine is excreted after hepatic acetylation and hydroxylation. t½= 6–17 hours. ADR:- GIT disturbances, malaise, headache, skin rash, leukopenia, impairment of folic acid absorption. Reversible infertility in men.

13. It causes remission of rheumatoid arthritis but it does not retard the progression of bone damage.

14. Mechanism of action:-suppression of T lymphocyte responses to mitogens, Decreased leukocyte chemotaxis, Stabilization of lysosomal enzymes, Inhibition of DNA and RNA synthesis, Trapping of free radicals. Pharmacokinetics:-rapidly absorbed but only 50% protein-bound in the plasma.

15. Extensively tissue-bound. Deaminated in the liver, t½ =45 days. Used in systemic & discoid lupus ereythematosus.

16. Half the patients treated respond, effects appear after a month. ADR:-ocular toxicity may occur at high dosages. Dyspepsia, nausea, vomiting, abdominal pain, rashes, and nightmares.

17. Wide range of cytokines are expressed in the joints of rheumatoid arthritis patients, the most important isTNFα. TNF α effects cellular function via activation of specific membrane-bound TNF receptors (TNFR1, TNFR2). Administered soluble TNF receptors, by combining with soluble TNF α, can inhibit the effects of the endogenous cytokine.

20. Infliximab is a chimeric (25% mouse, 75% human) monoclonal antibody that binds with high affinity to soluble and possibly membrane-bound TNF-α. Is given as an intravenous infusion every 8 weeks. The terminal half-life is 9–12 days.

21. Infliximab elicits up to a 62% incidence of human antichimeric antibodies. methotrexate ↓ human antichimeric antibodies. Infliximab is effective:- in rheumatoid arthritis ulcerative colitis psoriasis, psoriatic arthritis, juvenile chronic arthritis.

22. Infliximab plus methotrexate. ADR:-Upper respiratory tract infections, nausea, headache, sinusitis, rash, and cough, activation of latent tuberculosis, infusion site reactions

24. Quiz? Infliximab produces its antirheumatic effects by direct (A) Inhibition of cAMP phosphodiesterase in monocytic leukocytes (B) Selective inhibition of COX-2 (C) Enhancement of leukotriene synthesis at the expense of prostaglandin synthesis (D) Reduction of circulating active TNF-α levels (E) Inhibition of the production of autoantibodies

27. A 54-year-old woman presented with signs and symptoms consistent with an early stage of rheumatoid arthritis. The decision was made to initiate NSAID therapy.

28. Q1 Which of the following patient characteristics is a possible reason for the use of celecoxib in the treatment of her arthritis? (A) A history of a severe rash after treatment with a sulfonamide antibiotic (B) A history of gout (C) A history of peptic ulcer disease (D) A history of sudden onset of bronchospasm after treatment with aspirin (E) A history of type 2 diabetes

29. Q2 Although the patient's disease was adequately controlled with an NSAID and methotrexate for some time, her symptoms began to worsen and radiologic studies of her hands indicated progressive destruction in the joints of several fingers. Treatment with a new second-line agent for rheumatoid arthritis was considered. This drug is available only in a parenteral formulation; its mechanism of anti- inflammatory action is antagonism of tumor necrosis factor. The drug being considered is:- (A) hydroxychloroquine (B) infliximab (C) methotrexate (D) chloroquine (E) Sulfasalazine