Pharm II (Gout and RA)

Recurrent episodes of acute arthritis due to deposits of monosodium urate crystals.

Can be familial

• Metatarsophalangeal joint of the first toe is often
• involved but other joints can also be affected. The DIP is spared.

The end product of Purine metabolism.

Cold and acidic



•Neutrophils ingesting urate crystals secrete inflammatory mediators that lower the local pH and lead to further urate precipitation.

NSAIDS >Glucocorticoids> Colchicine

• •Indomethacin, Naproxen, Sulindac and Celecoxib are effective in the treatment of acute gout.
• Prednisone or betamethasone are commonly used orally.

•Intravenous methylprednisolone and intraarticular triamcinolone have been found equally effective.

• -It is a mitotic inhibitor
• -It also reduces leukocyte migration and decreases free radical formation.

•Colchicine can be used in low dose as a prophylactic therapy for chronic gout, to inhibit the occurrence of future attacks of gout.


-Diarrhea, Kidney and liver damage

• •1.Uricosuric drugs - accelerating the renal
• excretion of uric acid. Eg., Probenecid, Sulfinpyrazone

•2.reducing the conversion of purine to uric acid by xanthine oxidase. Eg., Allopurinol, Febuxostat

• is an uricosuric drug that competes with uric acid
• for reabsorption in PCT of kidney.

-good choice in underexcretors of uric acid. It is not a good choice in patients who are already excreting large amount of uric acid and in renal failure.

Allopurinol is the preferred and standard therapy for chronic gout.

• •Allopurinol and its metabolites are irreversible inhibitors of xanthine oxidase, an enzyme that converts
• hypoxanthine to xanthine and xanthine to uric acid.

It thus increases the concentrations of the more soluble form (Hypoxanthine) allowing for more excretion.

•Allopurinol inhibits the metabolism of mercaptopurine and azathioprine, that depend on xanthine oxidase.

• •The serious toxicity includes hypersensitivity reactions like:
• skin rashes, toxic epidermal necrosis and
• bone marrow suppression.

•Acute gout : NSAIDS, steroids and colchicine


•Prophylaxis : Probenecid, allopurinol and colchicine.

• Methotrexate
• Leflunomide
• Sulfasalazine
• Hydroxychloroquine
• Gold salts, Cyclosporine
• Corticosteroids

Etanercept, Infliximab, Adalimumab, Anakinra

Inhibits DHFR---> decreasing purine synthesis

• Hepatotoxicity occurs frequently
• It is also used in psoriasis and SLE

• -approved for the treatment of RA and inflammatory bowel diseases
• -It is a prodrug which is converted into sulfapyridine and 5-aminosalicylic acid (5-ASA).
• -Sulfapyridine is most active when treating RA
• -Inhibits the effects of IL-1 and TNF alpha

-Stevens Johnson syndrome and Aplastic anemia

• -Interfere with the activity of T lymphocytes
• -Decrease leucocytes chemotaxis
• -Stabilizes the lysosomal membranes
• -Interfere with DNA and RNA synthesis and trap free radicals.

• -Less toxic than chloroquine but long term use
• can cause retinopathy or corneal deposits.

• immunomodulatory agent that cause inhibition of dihydroorotate dehydrogenase the key enzyme in
• the pyrimidine synthesis

• - RA and Psoritic arthritis
• -can be used as a monotherapy or in combination
• with methotrexate.
• -Liver damage and BM supression

prevent the damage by suppressing the phagocytosis and lysosomal activity – thus retards the progression of bone and articular destruction.

-Azathioprine and cyclophosphamide

Screen for TB.

When giving anticytokin theropy there is a risk of Opportunist infections.

• -Blocks TNF-α
• -Blocks TNF α & β (is a fusion protein)
• -Blocks TNF-α
• -IL-1 receptor antagonist
• -Blocks costimulation--Prevents CD28 from binding CD80/86 (is a fusion protein)