Tag: Treatment For Gout

Treatment For Gout

TREATMENT FOR GOUT

Q. 1 Mechanism of action of colchicine is:
 A Suppresses immunity
 B Increased uric acid excretion
 C Decreased uric acid synthesis
 D None of the above
Q. 1 Mechanism of action of colchicine is:
 A Suppresses immunity
 B Increased uric acid excretion
 C Decreased uric acid synthesis
 D None of the above
Ans. A

Explanation:

Suppresses immunity


Q. 2 Probenecid
 A Does not decrease the renal excretion of pencillin
 B Does decrease the renal excretion of pencillin
 C Has no effect
 D At high doses increases and at low doses decreases
Q. 2 Probenecid
 A Does not decrease the renal excretion of pencillin
 B Does decrease the renal excretion of pencillin
 C Has no effect
 D At high doses increases and at low doses decreases
Ans. B

Explanation:

Does decrease the renal excretion of pencillin


Q. 3

Probenecid does NOT decrease the renal excretion of the following drug:

 A

Ketoprofen

 B

Methotrexate

 C

Rifampin

 D

Penicillin

Q. 3

Probenecid does NOT decrease the renal excretion of the following drug:

 A

Ketoprofen

 B

Methotrexate

 C

Rifampin

 D

Penicillin

Ans. C

Explanation:

Probenecid decreases the biliary secretion of rifampin, leading to higher plasma concentrations.
 
Probenecid inhibits the tubular secretion of drugs, such as:
  • Methotrexate
  • Active metabolite of clofibrate
  • Inactive glucuronide metabolites of NSAIDs such as naproxen, ketoprofen, and indomethacin
  • Penicillin
  • Cephalosporins
Ref: Grosser T., Smyth E. (2011). Chapter 34. Anti-inflammatory, Antipyretic, and Analgesic Agents; Pharmacotherapy of Gout. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

Quiz In Between


Q. 4

Febuxostat is indicated in the treatment of:

 A

Hyperkalemia

 B

Hyperuricemia

 C

Hypernatremia

 D

Hypercalcemia

Q. 4

Febuxostat is indicated in the treatment of:

 A

Hyperkalemia

 B

Hyperuricemia

 C

Hypernatremia

 D

Hypercalcemia

Ans. B

Explanation:

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.


Q. 5

A 44 year old businessman presents to a physician because of a markedly inflamed and painful right great toe.He states that he just returned from a convention, and had noticed increasing pain in his right foot during his plane trip home. Physical examination is remarkable for swelling and erythema of the right great toe as well as small nodules on the patient’s external ear. Aspiration of the metatarsal-phalangeal joint of the affected toe demonstrates needle-shaped negatively birefringent crystals. Which of the following agents would provide the most immediate relief for this patient?

 A

Allopurinol

 B

Aspirin

 C

Colchicine

 D

Probenecid

Q. 5

A 44 year old businessman presents to a physician because of a markedly inflamed and painful right great toe.He states that he just returned from a convention, and had noticed increasing pain in his right foot during his plane trip home. Physical examination is remarkable for swelling and erythema of the right great toe as well as small nodules on the patient’s external ear. Aspiration of the metatarsal-phalangeal joint of the affected toe demonstrates needle-shaped negatively birefringent crystals. Which of the following agents would provide the most immediate relief for this patient?

 A

Allopurinol

 B

Aspirin

 C

Colchicine

 D

Probenecid

Ans. C

Explanation:

The patient has gout, which is due to precipitation of monosodium urate crystals in joint spaces (notably the great toe) and soft tissues (causing tophi, which are often found on the external ears). Colchicine reduces the inflammation caused by the urate crystals by inhibiting leukocyte migration and phagocytosis secondary to an effect on microtubule assembly.
 
Allopurinol and its metabolite, oxypurinol, inhibit xanthine oxidase, the enzyme that forms uric acid from hypoxanthine. Therapy with this agent should be begun 1-2 weeks after the acute attack has subsided.
 
Aspirin competes with uric acid for tubular secretion, thereby decreasing urinary urate excretion and raising serum uric acid levels. At high doses (more than 2 gm daily) aspirin is a uricosuric.
 
Probenecid  and sulfinpyrazone are uricosuric agents, increasing the urinary excretion of uric acid, hence decreasing serum levels of the substance. Therapy with these agents should be begun 1-2 weeks after the acute attack has subsided.
 
Ref: Grosser T., Smyth E. (2011). Chapter 34. Anti-inflammatory, Antipyretic, and Analgesic Agents; Pharmacotherapy of Gout. In B.C. Knollmann (Ed), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

Q. 6

The uricosuric agent used for acute gout in a chronic renal failure patient is:

 A

Probenecid

 B

Colchicine

 C

Benzbromarone

 D

Aspirin

Q. 6

The uricosuric agent used for acute gout in a chronic renal failure patient is:

 A

Probenecid

 B

Colchicine

 C

Benzbromarone

 D

Aspirin

Ans. C

Explanation:

Uricosuric agents such as probenecid can be used in patients with good renal function who underexcrete uric acid.
 Probenecid is generally not effective in patients with serum creatinine levels >177 mol/L (2 mg/dL).
These patients may require allopurinol or benzbromarone. Benzbromarone is another uricosuric drug that is more effective in patients with renal failure.
 
Ref: Schumacher H.R., Chen L.X. (2012). Chapter 333. Gout and Other Crystal-Associated Arthropathies. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Quiz In Between


Q. 7

Ischemia/reperfusion (I/R) injury is considered to be a MAJOR mechanism for organ transplant failure. Allopurinol is used in organ preservation as:

 A

Antioxidant

 B

Preservative

 C

Free radical scavenger

 D

Precursor for energy metabolism

Q. 7

Ischemia/reperfusion (I/R) injury is considered to be a MAJOR mechanism for organ transplant failure. Allopurinol is used in organ preservation as:

 A

Antioxidant

 B

Preservative

 C

Free radical scavenger

 D

Precursor for energy metabolism

Ans. C

Explanation:

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.


Q. 8

 A person has severe pain and swelling in great toe, True statement is/are:

  1. Allopurinol used in acute control of gout
  2. Colchicine acts slowly
  3. Colchicine causes gastrointestinal disturbances
  4. High serum uric acid level may not be present
  5. Joint fluid aspiration is done for investigation
 A

1,2,3

 B

3,4,5

 C

2,4,5

 D

All are correct

Q. 8

 A person has severe pain and swelling in great toe, True statement is/are:

  1. Allopurinol used in acute control of gout
  2. Colchicine acts slowly
  3. Colchicine causes gastrointestinal disturbances
  4. High serum uric acid level may not be present
  5. Joint fluid aspiration is done for investigation
 A

1,2,3

 B

3,4,5

 C

2,4,5

 D

All are correct

Ans. B

Explanation:

“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”

Acute gout
Acute gout manifests as sudden onset of severe inflammation in a small joint ( commonest is metatarso- phalangeal joint of great toe) due to precipitation of urate crystals ( sodium biurate) in the joint space.
The joint become red, swollen and extremely painful, require immediate treatment.
 
Drugs used
For acute gout: NSAIDS, colchicine and corticosteroids
For chronic gout/hyperuricemia
Uricosuric: Probenecid, Sulfinpyrazone
Urea synthesis inhibitor: allopurinol
 
Allopurinol
Allopurinol as well as uricosurics should not be started during acute attack of gout.
It is first choice drug in chronic gout and can be used in both overproducers and under excretors of uric acid.
During the initial 1-2 months of treatment, attacks of acute gout are common probably due to fluctuating plasma urate levels.
With long term allopurinol therapy, tophi gradually disappear and nephropathy is halted, even reversed
 
Colchicine
Colchicine is the fastest acting drug to control an acute attack of gout; 1 mg orally followed by 0.25 m 1-3 hrly till controll of attack is achieved ( occurs in 4-12 hrs)
Nausea, vomiting, watery or bloody diarrhea and abdominal cramps occur as dose limiting adverse effect. Chronic therapy with colchicine is not recommended because it causes aplastic anaemia, agranulocytosis, myopathy and loss of hair.
 
Confirmation of diagnosis: Urate crystals in the aspirate from a joint or bursa, high serum uric acid crystals.
 
Ref: Maheshwari 3/e, Page 251; KDT 6/e, Page 205-10; Harrison’s 17/e, Page 2166.

Q. 9

All of the following are true about Lesch–Nyhan syndrome, EXCEPT:

 A

Affects almost solely males

 B

Excessive synthesis of purines is a feature

 C

Characterized by gouty arthritis

 D

Febuxostat is routinely used for treatment

Q. 9

All of the following are true about Lesch–Nyhan syndrome, EXCEPT:

 A

Affects almost solely males

 B

Excessive synthesis of purines is a feature

 C

Characterized by gouty arthritis

 D

Febuxostat is routinely used for treatment

Ans. D

Explanation:

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.

Febuxostat has been approved for use in the treatment of chronic hyperuricemia.
This drug appears to be more effective than allopurinol in preventing acute attacks of gout and reducing the size of the crystal deposits. 
 
Ref: Janson L.W., Tischler M.E. (2012). Chapter 4. Nucleosides, Nucleotides, DNA, and RNA. In L.W. Janson, M.E. Tischler (Eds), The Big Picture: Medical Biochemistry.

Quiz In Between


Q. 10

A 47-year-old male patient presents with painful arthritis in the right big toe and uric acid renal stones. He has been taking allopurinol for his condition. What biochemical defect would likely be found in this patient?

 A

A defect in urea synthesis

 B

An abnormality of the purine degradation pathway

 C

An inability to synthesize non-essential amino acids

 D

Defective topoisomerases

Q. 10

A 47-year-old male patient presents with painful arthritis in the right big toe and uric acid renal stones. He has been taking allopurinol for his condition. What biochemical defect would likely be found in this patient?

 A

A defect in urea synthesis

 B

An abnormality of the purine degradation pathway

 C

An inability to synthesize non-essential amino acids

 D

Defective topoisomerases

Ans. B

Explanation:

This patient has gout, characterized by painful joints due to the precipitation of uric acid crystals caused by excessive production of uric acid (a minority of cases are associated with underexcretion of uric acid). Kidney disease is also seen due to accumulation of uric acid in the tubules.

The disease mostly affects males, and is frequently treated with allopurinol, an inhibitor of xanthine oxidase. Xanthine oxidase catalyzes the sequential oxidation of hypoxanthine to xanthine to uric acid.
 
A defect in urea synthesis would result in the accumulation of ammonia.
Phenylketonuria is a disease in which tyrosine cannot be produced from phenylalanine. It is characterized by a musty body odor and mental retardation.
 
Defective topoisomerases would affect DNA unwinding, and therefore replication.
 
Ref: Rodwell V.W. (2011). Chapter 33. Metabolism of Purine & Pyrimidine Nucleotides. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.

 


Q. 11

Prolonged allopurinol therapy in a patient with gout is not indicated for –

 A

Acute gouty arthritis

 B

Tophi

 C

Urate nephropathy

 D

Evidence of bone/joint damage

Q. 11

Prolonged allopurinol therapy in a patient with gout is not indicated for –

 A

Acute gouty arthritis

 B

Tophi

 C

Urate nephropathy

 D

Evidence of bone/joint damage

Ans. A

Explanation:

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.


Q. 12

Allopurinol is used in the treatment of ‑

 A

Gout

 B

Hypothyroidism

 C

Hypertension

 D

Hyperlipidemia

Q. 12

Allopurinol is used in the treatment of ‑

 A

Gout

 B

Hypothyroidism

 C

Hypertension

 D

Hyperlipidemia

Ans. A

Explanation:

Ans. is ‘a’ i.e., Gout

Allopurinol is the DOC for chronic gout.

Quiz In Between


Q. 13

Best drug for chronic gout in patient with renal impairment is –

 A

Naproxen

 B

Probenecid

 C

Allopurinol

 D

Sulfinpyrazone

Q. 13

Best drug for chronic gout in patient with renal impairment is –

 A

Naproxen

 B

Probenecid

 C

Allopurinol

 D

Sulfinpyrazone

Ans. C

Explanation:

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.


Q. 14

Most common adverse effect of colchicine –

 A

Diarrhoea

 B

Peptic ulcer

 C

Dyspepsia

 D

Pulmonary fibrosis

Q. 14

Most common adverse effect of colchicine –

 A

Diarrhoea

 B

Peptic ulcer

 C

Dyspepsia

 D

Pulmonary fibrosis

Ans. A

Explanation:

Ans. is ‘a’ i.e., diarrhoea

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


Q. 15

Allopurinol prevents conversion of –

 A

Hypoxanthine to xanthine

 B

Xanthine to hypoxanthine

 C

Hypoxanthine to I.M.P

 D

All

Q. 15

Allopurinol prevents conversion of –

 A

Hypoxanthine to xanthine

 B

Xanthine to hypoxanthine

 C

Hypoxanthine to I.M.P

 D

All

Ans. A

Explanation:

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

Quiz In Between


Q. 16

A patient receiving allopurinol requires dose reduction of-

 A

6 mercaptopurine

 B

Cyclophosphamide

 C

Azathioprine

 D

a and c

Q. 16

A patient receiving allopurinol requires dose reduction of-

 A

6 mercaptopurine

 B

Cyclophosphamide

 C

Azathioprine

 D

a and c

Ans. D

Explanation:

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.


Q. 17

Which is an uricosuric drug-

 A

Allopurinol

 B

Probenecid

 C

Indomethacin

 D

Aspirin

Q. 17

Which is an uricosuric drug-

 A

Allopurinol

 B

Probenecid

 C

Indomethacin

 D

Aspirin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Probenecid

  • Uricosuric drugs are probenacid, sulfinpyrazone and benzbromarone.

Q. 18

Acute Gouty arthritis is seen early in treatment following –

 A

Probenecid

 B

Allopurinol

 C

Rasburicase

 D

All of the above

Q. 18

Acute Gouty arthritis is seen early in treatment following –

 A

Probenecid

 B

Allopurinol

 C

Rasburicase

 D

All of the above

Ans. D

Explanation:

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.

Quiz In Between


Q. 19

Febuxostat is used for ?

 A

Hyperkalemia

 B

Hyperuricemia

 C

Hypernatremia

 D

Hypercalcemia

Q. 19

Febuxostat is used for ?

 A

Hyperkalemia

 B

Hyperuricemia

 C

Hypernatremia

 D

Hypercalcemia

Ans. B

Explanation:

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.


Q. 20

Allopurinol is used in organ preservation as:

 A

Antioxidant

 B

Preservative

 C

Free radical scavenger

 D

Precursor for energy metabolism

Q. 20

Allopurinol is used in organ preservation as:

 A

Antioxidant

 B

Preservative

 C

Free radical scavenger

 D

Precursor for energy metabolism

Ans. C

Explanation:

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

Q. 21

All of the following Drugs are used in treatment of chronic gout, except:-

 A

Allopurinol

 B

Benzbromarone

 C

Pegloticase

 D

Methotrexate

Q. 21

All of the following Drugs are used in treatment of chronic gout, except:-

 A

Allopurinol

 B

Benzbromarone

 C

Pegloticase

 D

Methotrexate

Ans. D

Explanation:

Answer is D (Methotrexate):

To Lower Uric Acid Levels (Hypouricemic Therapy)

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

Quiz In Between


Q. 22

All of the following statements about Acute Attack in  gouty arthritis are true, except:-

 A

Joint aspirate reveals negative birefringent crystals

 B

Allopurinol should be started immediately

 C

Colchicine is known to provide relief

 D

Serum uric acid levels may be normal

Q. 22

All of the following statements about Acute Attack in  gouty arthritis are true, except:-

 A

Joint aspirate reveals negative birefringent crystals

 B

Allopurinol should be started immediately

 C

Colchicine is known to provide relief

 D

Serum uric acid levels may be normal

Ans. B

Explanation:

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

Definitive diagnosis of gout requires aspiration of the involved joint and demonstration of intracellular monosodium urate crystals in synovial fluid.

Under polarized light these are demonstrated as “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


Q. 23

Allopurinol acts by inhibiting:       

 A

Uric acid carboxylase

 B

Hypoxanthine oxidase

 C

Uric acid synthase

 D

Xanthine oxidase

Q. 23

Allopurinol acts by inhibiting:       

 A

Uric acid carboxylase

 B

Hypoxanthine oxidase

 C

Uric acid synthase

 D

Xanthine oxidase

Ans. D

Explanation:

Q. 24

Mechanism of action of colchicine is ‑

 A

Inhibits gouty inflammation

 B

Inhbits the release of chemotactic factors

 C

Inhibits granulocyte migration

 D

All the above

Q. 24

Mechanism of action of colchicine is ‑

 A

Inhibits gouty inflammation

 B

Inhbits the release of chemotactic factors

 C

Inhibits granulocyte migration

 D

All the above

Ans. D

Explanation:

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.

Quiz In Between


Q. 25

Probenecid interacts with ‑

 A

Streptomycin

 B

Ampicillin

 C

Vancomycin

 D

Erythromycin

Q. 25

Probenecid interacts with ‑

 A

Streptomycin

 B

Ampicillin

 C

Vancomycin

 D

Erythromycin

Ans. B

Explanation:

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.


Q. 26

Uricase used in the treatment of chronic gout is

 A

Allopurinol

 B

Benzbromarone

 C

Pegloticase

 D

Methotrexate

Q. 26

Uricase used in the treatment of chronic gout is

 A

Allopurinol

 B

Benzbromarone

 C

Pegloticase

 D

Methotrexate

Ans. C

Explanation:

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

Quiz In Between



Treatment For Gout

TREATMENT FOR GOUT


TREATMENT FOR GOUT

Introduction to Gout:

  • Characterized by elevated serum uric acid level.
  • Uric acid with low water solubility precipitates in joints, kidney & subcutaneous tissues.
  • Secondary hyperuricemia occurs.

2 mechanisms for secondary hyperuricemia:

1. Due to excessive uric acid production:

  • Eg: breakdown of proteins & nucleic acids during cancer chemotherapy).

2. Due to decreased uric acid excretion:

  • Eg: Use of thiazides, loop diuretics, ethambutol, clofibrate.

TREATMENT OF GOUT

Acute GOUT

Chronic GOUT

  • NSAID’s
  • Colchicine
  • Steroids
1. Drugs decreasing uric acid synthesis:

  • Purine based: Allopurinol.
  • Non-purine based: Febuxostat.

2. Drugs increasing uric acid secretion:

  • Probenecid
  • Sulfinpyrazone
  • Benzbromarone

3. Drugs increasing uric acid metabolism:

  • Rasburicase
  • Pegloticase

TREATMENT OF ACUTE GOUT:

  • Drugs: NSAID’s, Colchicine & Steroids.

Important drug details:

1. NSAIDs:

  • Indomethacin – DOC – Due to better tolerability.
  • Aspirin: Not preferred due to hyperuricemia.
  • Tolmetin: Ineffective.

2. Colchicine:

  • More effective & faster acting than NSAIDs.
  • Rarely used due to high toxicity.
  • MOA:
    • Acts by inhibiting granulocyte migration into inflamed joint.
    • Causes metaphase arrest.
  • Adverse effects:
    • Diarrhea – Most common & dose-limiting toxicity.
    • Cause kidney damage, myopathy & bone marrow depression.
  • Indications:
    • Prophylaxis of recurrent attacks of gout arthritis –
      • Daily colchicine dosage
    • In urate-lowering therapy –  
      • Suppresses gout attacks.
      • Due to abrupt change in serum uric acid precipitation.

3. Steroids:

  • Intra-articular corticosteroids used in refractory cases.

NEW ADVANCEMENTS:

  • IL-1 inhibitors:
    • Drugs: Anakinra, canakinumab & rilonacept.
    • Efficient for acute gout management.
    • Not FDA-approved.

TREATMENT OF CHRONIC GOUT:

Main strategy:

  • Decreasing serum uric acid –
    • By decreasing its synthesis.
    • By increasing its excretion & metabolism.

I) Drugs decreasing uric acid synthesis:

  • Drugs:
    • Purine based: Allopurinol.
    • Non-purine based: Febuxostat.

Individual drug description:

1. Allopurinol:

  • A newer hypoxanthine analog.
  • MOA: 
    • Decreases uric acid production, by inhibiting xanthine oxidase enzyme.
    • Metabolized by xanthine oxidase enzyme to alloxanthine.
    • Alloxanthine – Long acting inhibitor of xanthine oxidase.
  • Uses:
    • DOC for chronic gout in inter-critical period (between two acute attacks).
    • Combined with anticancer drugs – To decrease secondary hyperuricemia.
    • As an adjuvant to sodium stibogluconate in kala-azar treatment.
  • Drug interactions:
    • Dosage of 6-Mercaptopurine & azathioprine decreased on combination with allopurinol –
      • Since both are metabolized by xanthine oxidase.
    • Dose adjustment required in renal failure.
  • Contra-indications:
    • Acute Gout – 
      • Due to inhibitory effect of uric acid on cytokines release.
      • Also reduced uric acid aggravates inflammation.
  • Adverse effect:
    • Precipitation of acute gout attack (Most frequent)
    • Allopurinol hypersensitivity – Strong association with HLA–B*5801.
    • Drug rash (in 20% of patients) – Combined use of allopurinol & ampicillin.

2. Febuxostat:

  • Non-purine drug.
  • Administered without dose adjustment.
  • Causes abnormal liver function tests.

II) Drugs increasing uric acid excretion:

  • Also referred as “Uricosuric drugs”.
  • Drugs: Probenecid, sulfinpyrazone & benzbromarone.
  • MOA:
    • Acts as competitive inhibitors of uric acid reabsorption in proximal tubules.
  • Probenecid: Combined with penicillins, decreasing their renal excretion.
  • Contraindications:
    • Creatinine clearance is <50ml/min.
    • History of nephrolithiasis (uric acid or calcium stones).
    • Evidence of uric acid overproduction (> 800 mg of uric acid in a 24-hour urine collection).
  • Concurrent supply of abundant fluids & urinary alkalinizers advised –
    • Prevent uric acid crystal precipitation in kidney tubules.
    • Ineffective in presence of renal damage.

III) Drugs increasing uric acid metabolism:

  • Drugs: Rasburicase & Pegloticase.
  • Administered by i.v. route.
  • Indications: Only in patients with chronic gout refractory to other treatments.

Individual drug description:

  • Rasburicase:
    • Recombinant urate oxidase.
  • Urate oxidase (uricase):
    • An enzyme metabolizing insoluble uric acid to soluble allantoin in birds.
    • Absent in humans.
  • Pegloticase:
    • Drug is pegylated to increase duration of action.

Exam Important

  • Secondary hyperuricemia can occur due to excessive uric acid production or decreased uric acid excretion.
  • Drugs decreasing uric acid synthesis include Allopurinol & Febuxostat.
  • Allopurinol is a Purine based drug.
  • Febuxostat is a Non-purine based drug.
  • Drugs increasing uric acid secretion include Probenecid, Sulfinpyrazone & Benzbromarone.
  • Drugs increasing uric acid metabolism include Rasburicase & Pegloticase.
  • Indomethacin is DOC for acute GOUT, due to better tolerability.
  • Aspirin is not preferred for treatment of acute gout due to hyperuricemia.
  • Colchicine is more effective & faster acting than NSAIDs, useful for the treatment of GOUT.
  • Colchicine causes metaphase arrest.
  • Diarrhea is the most common & dose-limiting toxicity of colchicine.
  • Daily doses of Colchicine is used for prophylaxis of recurrent attacks of gout arthritis & also for urate-lowering therapy for suppressing gout attacks.
  • Main strategy for treatment of chronic gout includes decreasing serum uric acid, by decreasing its synthesis & by increasing its excretion & metabolism.
  • Allopurinol decreases uric acid production, by inhibiting xanthine oxidase enzyme.
  • Allopurinol is metabolized by xanthine oxidase enzyme to alloxanthine.
  • Alloxanthine is a long-acting inhibitor of xanthine oxidase.
  • Allopurinol is a DOC for chronic gout in inter-critical period (between two acute attacks).
  • Allopurinol is combined with anticancer drugs, to decrease secondary hyperuricemia.
  • Allopurinol is used as an adjuvant to sodium stibogluconate in kala-azar treatment.
  • Dosage of 6-Mercaptopurine & azathioprine decreased on combination with allopurinol, since both are metabolized by xanthine oxidase.
  • Allopurinol dose adjustment required in renal failure.
  • In acute gout, allopurinol is contraindicated, due to inhibitory effect of uric acid on cytokines release.
  • Most frequently allopurinol precipitates acute gout attack.
  • Uricosuric drugs includes probenecid, sulfinpyrazone & benzbromarone, competitively inhibiting uric acid reabsorption in proximal tubules.
  • Concurrent supply of abundant fluids & urinary alkalinizers advised for Probenecid, to prevent uric acid crystal precipitation in kidney tubules.
  • Rasburicase is a recombinant urate oxidase.
Don’t Forget to Solve all the previous Year Question asked on TREATMENT FOR GOUT

Module Below Start Quiz

Malcare WordPress Security