Treatment For Gout

Suppresses immunity

Does decrease the renal excretion of pencillin

• Methotrexate
• Active metabolite of clofibrate
• Inactive glucuronide metabolites of NSAIDs such as naproxen, ketoprofen, and indomethacin
• Penicillin
• Cephalosporins

Febuxostat is a non purine inhibitor of xanthine oxidase which is required for oxidation of hypoxanthine and xanthine to uric acid. It is usually used in gout especially in patients who are intolerant to allopurinol.

Other drugs used in the treatment of hyperuricemia:

• Uricosuric drugs
• Probenecid
• Sulfinpyrazone

Uric acid synthesis inhibitor

• Allopurinol

Ref: The Rheumatology Handbook By Margaret Callan, page 422.

The most commonly used solution for organ storage and flushing is the University of Wisconsin solution that contains lactobionate, raffinose, adenosine (a precursor for ATP generation), magnesium sulfate (to retard calcium influx), glutathione (as an antioxidant), and allopurinol (to inhibit xanthine oxidase induced reactive oxygen species (ROS) formation).

Ref: Immunobiology of Organ Transplantation edited by David S. Wilkes, William J. Burlingham, 2004, Page 548, 560.

“serum uric acid levels can be normal or low at the time of acute attack”. This limits the value of serum uric acid determination for the diagnosis of gout.

Nevertheless, serum urate levels are almost always elevated at some time and are important to use to follow the course of hyperuricemic therapy”

Lesch–Nyhan syndrome is a genetic disease, affecting almost solely males, of excessive synthesis of purines because of defective recycling and, therefore, uric acid production from their breakdown.

Lesch–Nyhan syndrome is characterized by gouty arthritis but, in addition, affects the brain, resulting in mental retardation, loss of control of arm/leg/face movements, aggressive behavior, and self-mutilation by biting and scratching.

Successful treatment of this disorder is still being sought.

Ans. is ‘a’ i.e., Acute gouty arthritis

o “Allopurinol as well as uricosuries should not be started during acute attack of gout”.             –

o Tophi, urate nephropathy and bone & joint damage are seen in chronic gout.

o Allopurinol is the drug of choice for chronic gout.

Ans. is ‘a’ i.e., Gout

Allopurinol is the DOC for chronic gout.

Ans. is ‘c’ i.e., Allopurinol

o NSAIDs like naproxen have no role in chronic gout.

o Uricosuric drugs like probenecid and sulfinpyrazone are ineffective in the presence of renal insufficiency.

o Allopurinol is drug of choice for most cases of chronic gout.

Ans. is ‘a’ i.e., diarrhoea

“Nausea, vomiting, diarrhea and abdominal pain are the most common untoward effects of colchicine”. – Goodman & Gilman

Ans. is ‘a’ i.e., Hypoxanthine to xanthine

Ans. is ‘a’ i.e., 6 mercaptopurine; ‘c’ i.e., Azathioprine

o Allopurinol inhibits the degradation of 6-mercaptopurine and azathioprine, their doses should be reduced.

Ans. is ‘b’ i.e., Probenecid

• Uricosuric drugs are probenacid, sulfinpyrazone and benzbromarone.

All of the above

• Rapid lowering of urate level in chronic gout, by any means, may precipitate an attack of acute gout, probably by causing the dissolution of tophi.

o It is therefore usual to give prophylactic suppressive treatment with indomethacine, colchicine or steroid cover during first 2 months of allopurinol or uricosurics.

o Amongs the given options, allopurinol, probenecid and Rasburicase are the drugs that lower serum urate level.

• So, all three can precipitate acute gout. However, among these three, allopurinol is used most commonly therefore is the best answer here.

Ans. is ‘b’ i.e., Hyperuricemia

Febuxostat is a urate lowering drug, an inhibitor of xanthine oxidase that is indicated for use in the treatment of hyperuricemia and chronic gout.

Ans is c i.e. Free radical scavenger 

Organ preservation is the supply line for organ transplantation. Currently, the liver, pancreas, and kidney can be successfully preserved for up to two days by flushing the organs with the University of Wisconsin (UW) solution and storing them at hypothermia (0-5° C). The UW solution is effective because it uses a number of cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch) that prevent the cells from swelling during cold ischemic storage. Additionally, the UW solution contains glutathione, allopurinol and adenosine, agents that may stimulate recovery of normal metabolism upon reperfusion by augmenting the antioxidant capacity of the organs (glutathione) or by stimulating high-energy phosphate generation (adenosine) upon reperfusion and allopurinol as free-radical scavenger.

• Glutathione            as antioxidant
• Adenosine              as precursor for energy metabolism
• Allopurinol              as free-radical scavenger

Answer is D (Methotrexate):

To decrease production of uric acid (Xanthine Oxidase Inhibitors)

• Allopurinol(Purine analogue)
• Febuxostat (Non-purine selective inhibitor of xanthine oxidase)

To increase the excretion of uric acid (Uricosurics)

• Probenecid
• Sulfinpyrazone
• Benzbromarone

To increase conversion of Uric acid to Allantoin which is far more soluble (Uricase)

• Pegloticase

Answer is B (Allopurinol should be started immediately):

Allopurinol should not be started immediately in acute attack of gout as it may precipitate acute symptoms.

The mainstay of treatment in acute gouty arthritis is the administration of anti inflammatory drugs such as NSAID, Cochicine and /or glucocorticoids.

Allopurinol should not be started immediately in Acute attack of Gout

Allopurinol should never be started in acute gout as it may actually precipitate an acute attack.

Anti inflammatory drugs such as NSAIDs are the drugs of choice in acute gout.

Joint aspirate typically reveals strongly negative birefringent needle shaped crystals

Tophi are aggregates of monosodium urate monohydrate crystals that form in extra articular and articular structures and cause deformity and destruction of hard and soft tissue.

Serum uric acid levels may be normal in Acute Gout

Gout is caused whenever; synovial fluid is supersaturated with uric acid, irrespective of serum concentration of uric acid.

The serum levels of uric acid can be normal or even low at the time of an attack and hence its determination is not diagnostic for gout.

`Serum uric acid levels may be normal or low at the time of an acute attack, as inflammatory cytokines can be uricosuric and effective initiation of hypourecemic therapy can precipitate attacks.

This limits the value of serum uric acid determination for the diagnosis of gout ‘- Harrison’s 18th/2838

Ans. is ‘d’ i.e., All the above

Colchicine

• It is neither analgesic nor anti inflammatory.
• It specifically inhibits gouty inflammation.
• It is inhibits release of chemoattractant molecules.
• It inhibits granulocyte migration into the joint.
• It is antimitotic causes metaphase arrest by binding to microtubules.
• It increases gut motility.

Ans. is ‘b’ i.e., Ampicillin

Interactions of probenecid

1. Probenecid inhibits urinary excretion of penicillins, cephalosporins, methotrexate, sulfonamides and indomethacin.
2. It inhibits biliary excretion of rifampicin.
3. Salicylates block uricosuric action of probenecid.
4. Probenecid inhibits tubular secretion of nitrofurantoin.
5. Pyrazinamide and ethambutol may interfere with uricosuric action of probenecid.

Note : Ampicillin is a penicillin.

Ans. is ‘c^‘ i.e., Pegloticase

Pegloticase is a recombinant mammalian Uricase linked to polyethylene glycol (PEG) approved for the treatment

• of Hyperuricemia in patients with treatment refractory gout.
• Pegloticase facilitates the conversion of Uric acid into allantoin, which is far more soluble. Pegloticase is approved for intravenous administration and its use is associated with rapid and marked decline in serum uric acid levels.

Agents inhibiting IL-1 action are used for the treatment of refractory Gout

• Anakinra
• Canakinumab