Prophylaxis and Treatment of Gout

Gout

" Kings disease"

Definition:

Gout is a metabolic disease charactrized by recurrent episodes of acute arthiritis due to depositis of ureate crystals in joints and cartilage. it is usually associated with high serum levels of uric acid.

Smptoms

• Gout causes sudden severe pain, and is usually at the base of the big toe, but it may affect another joint, especially joints damaged by other conditions such as osteoarthritis inflammation.

• It can affect lobe of ears and skin surrounding the joint, especially the joints of the fingers or the back of the heel 

• The symptoms begin with sharp pain in the affected joints with swelling and redness around it,and these symptoms may be associated with high temperature (fever)and in most cases these crises occur in the evening, but the symptoms go away permanently  within a week or more to re-appear again at intervals over several weeks or months or years.

Aim of treatment:

1. To relieve acute gouty attacks.
2. To prevent recurrent gouty episodes and urate lithiasis.

Treatment of acute gout:

1)Non-steriodal anti-inflammatory drugs(NSAIDs):

• All NSAIDs except aspirin, salicylates, and tolmetin can successfully treat acute gouty episodes.
• Oxaprozin lowers serum uric acid, it should not be given to patients with uric acid stones because it increase uric acid excretion in the urine.
• Indomethacin is commonly used.

>>>N.B.

• SAIDs may be given to patients unable to take NSAIDs.

2)Colchicine:

• Colchicine relieve the pain and inflammation of gouty arthiritis in 12-24 hours without altering the metabolism or excretion of urates and without other analgesic effects.
• It acts by inhibition of leukocyte migration and phagocytosis.

Indications:

1. Treatment of acute gout(largely replaced by NSAIDs).
2. Colchicine is now used for the prophylaxis episodes of gouty arthiritis.
3. Has a mild beneficial effect in sarcoid arthiritis and in hepatic cirrhosis.
4. Although it can be given intravenously, this route should be used cautiously because of increased bone marrow toxicity.

Adverse effects:

• Diarrhea.

• Nausia, Vomiting and abdominal pain.

• Rarely: hair loss and bone marrow depression as well as peripheral neuritis and myopathy.

• A cute intoxication after overdoses is characterized by burning throat pain, blood diarrhea, shock, hematuria, and oliguri. fetal ascending CNS depression has been reported. Treatment is supportive(Colchicine has a small fatal dose).

Prophylaxis:

1)Uricosuric Agents:

Probenecid and sulfinpyrazone are uricosuric drugs(increase urine secretion of uric acid).
In a patient who excretes large amounts of uric acid, uricosuric should't be used.

Advese effects:

1. Gastrointestinal irritation(should be given with food to reduce irritation).
2. Rash.
3. Rarely:aplastic anemia.
4. Nephrotoxicity may occur with Probenecid.

Contraindications&Cautions:

• It is essential to maintain a large urine volume to minimize the possibility of urinary stone formation. Also alkalinization of urine  decreases incidence of stone formation.

• N.B.

• Because aspirin in doses less than 2,6 g daily causes net retention of uric acid, it shouldn't be used for analgesia in patients with gout.

2)Allopuinol:

Mechanism of action:

• inhibit synthesis of uric acid (by inhibition of xanthine oxidase enzyme).

Indications:

1. Prophylaxis of gout: when starting allopurinol, colchicine should also be used untill serum uric acid is decreased to less than 6 mg/dl. Therefore colchicine can be stopped, while allopurinol is continued.
2. Antiprotozoal agent.

Advese Effects:

1. Acute attack of gout during initiation of trearment(add colchicines or NSAID prophylactically).
2. Nusia, vomiting and diarrhea.
3. Preipheral neuritis and necrotizing vasculitis.
4. Bone marrow depression and, rarely, aplastic anemia may also occur.
5. Hepatic toxicity and interstitial nephritis have been reported.
6. Allergic skin reaction.

Interactions&Cautions:

1. When azathioprine is given concomitantly with allopurinol, its dosage must be reduced by about 75%.
2. Allopurinol may increase the effect of cyclophosphhamide.
3. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants.

3)Febuxostat:

• Inhibitor of xanthine oxidase therefore reduces the formation of uric acid.

Adverse Effects:

• As with allopurinol, prophylactic treatment with colchicine or NSAIDs should start at the begining of treatment to avoid gout flares.

• The most frequent adverse events are liver function abnormalities, diarrhea, headache,and nusia. Febuxostat appear to be well tolerated in patients with a history of allopurinol intolerance.

N.B.

• Febuxostat is awaiting FDA approval for the treatment of chronic gout.It is the first new drug for the treatment of gout in over 40 years.