504-2 Pharm: Gout And Rheumatoid Arthritis

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504-2 PHARM: GOUT and RHEUMATOID ARTHRITIS

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504-2 PHARM: GOUT and RHEUMATOID ARTHRITIS

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Primary Gout

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1. mainly in men
2. genetic disturbance in purine metabolism
3. over production or under secretion of uric acid

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Secondary Gout

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1. hyperurecemia
2. secondary to Lesch-Nyhan syndrome

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Hyperurecemia

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Normal level: 3-7 mg/dl

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Sequela of chronic gout

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Copy diagram

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Indomethacin (indocin)

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1. an NSAID
2. used for Tx of acute attack of gouty arthritis.

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Aspirin

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Contraindicated in gout

Low doses inhibit secretion of uric acid.

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Therapeutic uses of Colchicine

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1. relief from attacks of gouty arthritis
2. used prophylactically when initiating therapy with probenecid or allopurinol
3. anti-inflammatory effect selective for gout

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Mechanism of colchicine

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Inhibits acute inflammatory rxn by disrupting microtubules in inflammatory cells.

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Significant adverse rxn of colchicine are due to?

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Anti-mitotic action

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Therapeutic uses of Probenecid

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1. reduces hyperuricemia in chronic gout
2. dissolution and resorption of urate deposits

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Mechanism of action of probenecid

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Inhibits reabsorption of uric acid in proximal tubule.

Depress urate excretion due to inhibition of secretory transporter.

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Side effects of probenecid

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1. can increase frequency of gouty attacks.
2. deposition of urate crystals in ureter.

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Allopurinol

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1. structural analog of hypoxanthine
2. rapidly oxidized to ALLOXANTHINE by xanthine oxidase

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Mechanism of allopurinol

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Both allopurinol and alloxanthine inhibit xanthine oxidase.

Prevents the enzymatic formation of uric acid.

Increases excretion of hypoxanthine and xanthine.

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Therapeutic uses of allopurinol

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1. reduces hyperurecemia
2. compatible with prebenecid

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Other therapies of gout

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1. avoid purine rich food
2. avoid excessive alcohol
3. increase fluid intake
4. alkalinize urine

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Anti-inflammatory drugs used in Tx of rheumatoid arthritis

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1. NSAIDs
2. immunosuppressants
3. adrenal corticosteroids
4. antagonists of tumor necrosis factor alpha

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NSAIDs mechanism of action when used for rheumatoid arthritis.

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NSAIDs prevent synthesis of PGs and thromboxanes by inhibition of FA cyclooxygenase (COXs)

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Which one is a selective COX-2 inhibitor?

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Celecoxib (celebrex)

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Methotrexate

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A folate antimetabolite

Used as chemotherapeutic and immunosuppressive drug.

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Azathioprine (imuran)

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An anti-proliferative drug

Purine anti-metabolite

Immunosuppressive action attenuates arthritic inflammation.

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What are some examples of adrenal corticosteroids?

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1. cortisone
2. dexamethasone (decadrone)
3. prednisone

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What are the effects of glucocorticoids?

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Have potent anti-inflammatory actions to provide pain relief.

NOTE: side effects may include Cushing syndrome

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TNF alpha

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Pro-inflammatory immune cytokine with a role in rheumatoid arthritis.

Drugs bind to TNF alpha and prevent it from binding to its receptor.

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Etanercept

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Engineered to link the human gene for soluble TNF receptor 2 to the gene for the Fc component of human immunoglobulin G1 (IgG1).

It's a TNF alpha inhibitor

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Infliximab

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Anti-TNF alpha antibody