# 3 Anti-Rheumatic/ Gout 9-8-06

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DMARDS (disease-modifying anti-rheumatic drugs)

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1) gold
2) antimalarial agents
3) chelators
4) cytotoxic agents

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gold alter fuuctions and morphology of?

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macrophage

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gold accumulate in macrophages in the?

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inflamed synovium

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plasma t 1/2 of gold?

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7 days (increases weeks or months)

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IM gold

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1) Aurothioglucose (Solganal)
2) Gold sodium thiomalate (Myochrysine)

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PO gold

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Auranofin (Ridaura)

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SE of gold

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1) dermatitis (most common)
2) stomatitis
3) chrysiasis (bluish-gray pigmentation)
4) bone marrow depression
5) nephrotic syndrome

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antimalarial agent?

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Hydroxychloroquine (Plaquenil)

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mechanism of Plaquenil?

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to stabilize lysosomal membrane

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SE of Plaquenil?

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1) serious damage to retina
2) dermatitis
3) ototoxicity
4) neuromyopathy

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Chelator?

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D-penicillamine (Cuprimine)

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D-penicillamine inhibit enzymes that are?

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pyridoxal-dependent; increases pyridoxine requirement

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mechanism of D-penicillamine?

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may affect immune system

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SE of D-penicillamine?

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1) loss of taste perception
2) nephrotoxicity
3) myasthenia-like syndrome
4) rash
5) thrombocytopenia
6) leukopenia

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cytotoxic agents?

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1) Azathioprine (Imuran)
2) Methotrexate (Rheumatrex)

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mecahnism of cytotoxic agents?

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1) direct anti-infla effect
2) suppress or modify immune response

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serious SE of cytotoxic agents?

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1) bone marrow depression
2) sterility
3) carcinogenic
4) mutagenic

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Why aggressive early tx of cytotoxic agents is beneficial?

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becuase it can prevent major manifestations of RA before irreversible damage become prevalent

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Which medication of DMARDS has the best benefit-to-risk ratio?

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Methotrexane (Rheumatrex)

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drugs used in therapy of acute gout attacks?

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1) Colchicine
2) NSAIDS

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drugs that increase urate excretion?

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= uricosurics
1) Probenecid (Benemid)
2) Sulfinpyrazone (Anturane)

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drug that decrease uric acid production?

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Allopurinol (Zyloprim)

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Colochicine?

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Alkaloid of Colchicum autumnale
1) Autumn crocus
2) Meadow saffron

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Colchicine binds to?

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tubulin and disrupts mitotic spindles, causes depolymerization

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SE of colchicine
(cells with high rates of division are affected)

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1) N/V
2) abdominal pain
3) diarrhea
4) hemorrhagic gastroenteritis
5) vascular damage
6) renal toxicity
7) muscular depression
8) paralysis

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Probenecid and Sulfinpyrazone block reabsorption of?

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urate in the renal proximal tubule

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Probenecid is the prototype inhibitor of?

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organic anion secretion (used to increase t1/2 of PCN)

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initiation of Probenecid and Sulfinpyrazone may precipitate?

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an acute gout attach
(prophylactic use of colchicine or and NSAID can prevent the attack)

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mechanism of Allopurinol (Zyloprim)

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to inhibit XO (xanthine oxidase)

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XO converts?

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1) hypoxanthine to
2) xanthine to
3) uric acid

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action of Allopurinol?

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1) increase [ ] of the more water soluble hypoxanthine and xanthine
2) decrease [ ] of the less soluble uric acid

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Allopurinol is generally used in?

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severe chronic gout

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Allopurinol is used in prevention of hyperuricemia in pts with?

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leukemia and some other cancers undergoing chemo with cytotoxic agents

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SE of Allopurinol?

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1) skin rash
2) GI problems
3) rare - bone marrow depression
4) acute gout attack with initiation of therapy