Gout
Definition
Gout is a recurrent arthritis that result from deposition in or about the
joint of sodium urate crystals from supersaturarated hyperuricemic
body fluids
Drugs used in the treatment of gout
1--Anti-inflammatory drugs used for gout -
(NSAIDs.......Steroids.....Colchicine)
2--Uricousuric agents ( Probenecid..... Sulfinpyrazone)
3--Uric acid synthesis inhibitors (Allopurinol )
1- Anti-inflammatory drugs used for gout
A- NSAIDs=Non-steroidal anti-inflammatory drugs
...NSAIDs as indomethacin are used in a c u t e gouty arthritis
.NSAIDs reduce inflammation by inhibiting prostaglandins synthesis
via inhibition of cyclooxygenase 2.
B- Steroids ( Glucocorticoids as prednisone )
...Steroids ( Glucocorticoids as prednisone) are used in a c u t e
gout to reduce inflammation by reducing prostaglandins and
leukotrienes synthesis via inhibition of phospholipase A 2.
C- Colchicine
...Cholchicine is useful in a c u t e gout but the possible severe
diarhoea and gastric irritation limit its use. Cholchicine reduces
inflammation by reducing leukocyte migration to the site of
inflammation because it is a selective inhibitor of microtubule
assembly.
Toxicity of anti-inflammatory antigout (side effects)
...NSAIDs toxicity.......( Renal damage ......Bone marrow toxicity )
...Steroids..... ( Behavioral changes.....Impaired glucose tolerance )
...Colchicine.....( Diarhoea.....Liver damage .....Renal damage )
2- Uricousuric agents
Drugs
...A- Probenecid
...B - Sulfinpyrazone
Mechanism of uricousuric agents action
They act by competing with uric acid reabsorption which is acheived
by the weak acid transport mechanism in the proximal convoluted
tubules of the kidney.
(At low doses, probenecid and sulfinpyrazone being acids may
increase uric acid concentration in in the blood but here by competing
with uric acid secretion .....Aspirin , another week acid, can do that in
every dose, so aspirin is not useful in gout ).
Clinical indications of uricosuric agents
1.Chronic gout
2. Not useful in acute gout
Toxicity of uricosuric agents (side effects)
1-Precipitation of acute gouty arthritis during early face of treatment
because reduction of the level of uric acid in the blood by the
uricosuric agents leads to shifting of the uric acid, which was
accumalated in other tissues, shifting it to the blood and
precipitaion in the joints .This can be avoided by simultaneous use of
an anti-inflamatory drug as indomethacin or colchicine.
2-Being sulfonamides , they can cause allergenicity like other
sulfonamides.
3 - Uric acid synthesis inhibitors ( Allopurinol )
Mechanism of action
Allopurinol is an isomer for hypoxanthine .Hypoxanthine originates
from DNA & RNA metabolism .Hypoxanthine is converted to xanthine
by xanthine oxidase. Xanthine is then converted to uric acid by the
same enzyme. Allopurinol is converted to alloxanthine by xanthine
oxidase (allopurinol is an irreversible inhibitor of this
enzyme).Inhibition of xanthine oxidase increases the concentration of
the more soluble hypoxanthine and xanthine and decreases the
cocentration of the less soluble uric acid. As a result there is less
likelihood of precipitation of uric acid crystals in the joints & tissues.
Clinical use of allopurinol
1-Allopurinol is given orally in the management of chronic gout. It is
usually withheld for 2 weeks after acute gouty arthritis.
2-Cancer chemotherapy : to decrease the formation of uric acid from
purines released by the death of neoplastic cells.
Toxicity of allopurinol (side effects)
1-Precipitation of acute gouty arthritis during early face of treatment
(because reduction of the level of uric acid in the blood by allopurinol
leads to shifting of the uric acid, which was accumalated in other
tissues, shifting it to the blood and its precipitation in the joints).
2- GIT disturbances.
3-Rash
4-Rare adverse effects ---peripheral neuritis ---vasculitis ---bone
marrow depression
Drug interactions with allopurinol
Allopurinol inhibits the metabolism of mercaptopurine & azathioprine
-drugs which depend on xanthine oxidase for their elimination-.