Module 7 Pharm

Front 1

Etiology of gout?

Back 1

1. Familial metabolic disease
-- plasma urate comes from the metabolism of purines (mostly endogenous from breakdown of nucleic acid)
-- pts w/ grossly elevated plasma urate concentrations may never develop gout
-- pts w/ gout may have relstively normal plasma urate concentration

2. Acute bouts of arthritis result from the deposition of urate crystals in joints
-- synovial fluid is acidic, and acidic environment causes urate to form crystals
-- urate crystals are phagocytosed by synoviocytes w/ subsequent release of PGs, lysosomal enzymes and IL-1
-- chemoattractants pull PMN leukocytes into the joint w/ amplification of the inflammation
-- in later stages, macrophages appear, ingest urate crystals and release more inflamm cmpds
-- ultimate sequelae are inflammationpain and the erosion of bone and cartilage

3. Uric acid stones may form in the kidneys since the urine is normally acidic

Front 2

Gout therapy is indicated for…?

Back 2

Patients w/ hyperuricemia that is associated w/ gout and renal lithiasis

Front 3

Gout therapy is aimed at…?

Back 3

1. suppression of leukocyte activation
-- COLCHICINE
-- INDOMETHACIN

2. increasing renal urate excretion
-- PROBENACID

3. reducing urate production
-- ALLOPURINOL

Front 4

Colchicine MOA?

Back 4

1. binds to intracellular protein tubulin to prevent polymerization into microtubules

2. inhibits leukocyte migration and phagocytosis

Front 5

Colchicine therapeutic use?

Back 5

1. treat acute attacks

2. prophylaxis of recurrent episodes when treatment w/ a uricosuric drug + allopurinol is not sufficient to prevent attacks

Front 6

Colchicine side effects?

Back 6

Diarrhea – indomethacin often used in place for acute attacks b/c of the diarrhea

Abdominal pain

Alopecia

Bone marrow depression

Myopathy

Front 7

Indomethacin MOA?

Back 7

NSAID

1. inhibition of PG synthesis prevents the phagocytosis of urate crystals by synoviocytes and macrophages

2. prevention of the transcription of genes for many mediators of inflammation

Front 8

Indomethacin therapeutic use?

Back 8

1. initial therapy

2. an alternative to colchicines if the latter drug is ineffective or causes too much discomfort

Front 9

What is a uricosuric drug?

Back 9

Causes renal uric acid secretion

1. uric acid is freely filtered at the glomerulus and then completely reabsorbed before being secreted by the acid transport system of the proximal tubule

2. about 75% of secreted urate is reabsorbed

3. uric acid secretion is not reduced in CRF as long as the GFR remains above 15ml/min

Front 10

Probenacid MOA?

Back 10

1. uricosuric drugs affect urate transport such that the net reabsorption pf uric acid is decreased

2. renal uric acid excretion increases

3. size of the total body urate pool decreases even though plasma urate may not fall much

Front 11

Pharmacologic effects of probenacid?

Back 11

1. Tophaceous urate deposits are reabsorbed, but renal urate stones may form as the urinary urate concentration increasses

2. urate stone formation can be reduced by making the urine alkaline w/ Na or K bicarbonate, Na or K citrate or acetazolamide

3. joint inflammation remits and bone remineralizes

Front 12

Probenacid indications and use?

Back 12

1. therapy begun if several acute attacks have occurred, if tophi appear, or if plasma urate is greatly elevated

2. begin therapy 2-3 weeks after an acute attack

Front 13

Probenacid adverse effects?

Back 13

1. increased urinary urate can cause urate stones to form

2. GI irritation

Front 14

Allopurinol MOA?

Back 14

1. inhibits xanthine oxidase, the enzyme that converts hypoxanthine and xanthine to uric acid

2. size of the urate pool and plasma urate drop whereas the concentration of the more water-soluble cmpds hypoxanthine and xanthine increases

Front 15

Pharmocological effects of allopurinol?

Back 15

1. reduces serum urate w/o increasing renal uric acid excretion

2. tophaceous urate deposits are reabsorbed

3. joint inflamm remits and bone remineralizes

Front 16

Therapeutic indications for allopurinol?

Back 16

1. chronic tophaceous gout

2. grossly elevated plasma uric acid

3. when probenacid cannot be used due to adverse S/Es

4. recurrent urate stones

5. patients w/ poor renal fxn

6. used to prevent the increase in plasma urate concentration deposits when pts w/ leukemias or lymphomas are treated w/ radiation or antineoplastic drugs

Front 17

Adverse S/Es of allopurinol?

Back 17

1. acute attacks may appear soon after tx is begun, so colchicines may be required if the pt is not receiving a uricosuric agent

2. GI disturbance

3. if mercaptopurines are being given for chemo, their dose must be reduced to about 25% of normal since allopurinol will decrease their rate of metabolism

Front 18

Summary of gout treatment?

Back 18

Acute attacks: Colchicine or Indomethacine

Chronic therapy: probenacid and/or allopurinol