Colchicine in Gout Treatment

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Questions and Answers

What is the primary goal of colchicine in the treatment of gout?

To provide rapid relief from acute gouty attacks (correct)

To enhance plasma protein binding

To increase serum urate levels

To diagnose chronic osteoarthritis

How does colchicine exert its anti-inflammatory effects?

By enhancing neutrophil chemotaxis

By inhibiting phospholipase A2 (correct)

By stimulating prostaglandin production

By blocking serum urate absorption

What is the recommended prophylactic dose of colchicine for patients with normal renal function?

0.5 mg three times a day

1.0 mg once daily

1.2 mg daily

0.6 mg once or twice daily (correct)

Which of the following is NOT an indication for colchicine therapy?

Treatment of rheumatoid arthritis Signup and view all the answers

What is the half-life of colchicine after oral administration?

4 hours Signup and view all the answers

Which mechanism contributes to colchicine's ability to prevent inflammation?

Inhibition of leukocyte migration Signup and view all the answers

In which patient condition should colchicine be used with caution?

Patients with liver disease Signup and view all the answers

What role does colchicine play when initiating hypouricemic therapy?

It aids in preventing recurrent gout flares Signup and view all the answers

In which of the following conditions should the dose of colchicine be reduced or avoided?

Severe hepatic disease Signup and view all the answers

Which of the following medications is known as a CYP 3A4 inhibitor and poses a risk when used with colchicine?

Clarithromycin Signup and view all the answers

What is a common adverse effect associated with chronic use of colchicine?

Hemorrhagic gastroenteritis Signup and view all the answers

Which of the following therapies can safely be used in conjunction with allopurinol for patients with severe tophaceous gout?

Probenecid Signup and view all the answers

What is one of the effects of colchicine toxicity that is associated with renal insufficiency?

Neuromyopathy Signup and view all the answers

What should be done to minimize the risk of acute gouty attacks when initiating uric acid-lowering therapy?

Gradual dose increases Signup and view all the answers

Which of the following describes the purpose of xanthine oxidase inhibitors like allopurinol?

Inhibit the synthesis of uric acid Signup and view all the answers

Which side effect related to colchicine can affect fertility?

Both B and C Signup and view all the answers

What is the primary mechanism by which uricosuric drugs increase urinary excretion of uric acid?

Inhibition of URAT1 and GLUT9 Signup and view all the answers

Which condition is most likely an indication for uricosuric therapy?

Hyperuricemia secondary to underexcretion of uric acid Signup and view all the answers

How does urine alkalinization affect uricosuric therapy?

It reduces the risk of nephropathy. Signup and view all the answers

Which of the following medications can be safely used in conjunction with uricosuric therapy?

Fenofibrate Signup and view all the answers

What is a significant consideration when prescribing losartan for patients with gout?

It lowers blood pressure without raising uric acid. Signup and view all the answers

Which of the following is a notable pharmacokinetic property of febuxostat?

It has a longer half-life of 14 to 28 hours. Signup and view all the answers

What level of urinary uric acid is indicative of underexcretion in patients with gout?

800 mg in a 24-hour urine collection Signup and view all the answers

Which uricosuric drug acts primarily by inhibiting tubular reabsorption of urate?

Probenecid Signup and view all the answers

Study Notes

Hypouricemic Agents and Colchicine

Hypouricemic agents are drugs used to lower serum urate levels.
Colchicine comes from the Colchicum autumnale plant.
Colchicine has been used for centuries to treat acute gout and joint pain.
The clinical response to colchicine was initially a diagnostic tool for gout.

Sites of Action for Drugs

Drugs used to lower serum urate levels work at various points in the purine metabolism pathway.
Purines are metabolized to hypoxanthine and xanthine, then further to uric acid.
Xanthine oxidase inhibitors prevent uric acid production.
Uricosurics increase renal excretion of uric acid.
Uricase converts uric acid to allantoin, which is more readily excreted.
Tissue deposition and inflammation (tophi formation) from uric acid are also targeted.
Drugs can also inhibit processes such as phagocytosis of uric acid crystals.

Goals of Gout Treatment

Acute gout attacks require rapid pain relief and restoration of joint function (NSAIDS, corticosteroids, colchicine are often used).
Long-term prevention of recurrent attacks and prevention of destructive arthropathy, tophi formation, and nephrolithiasis is achieved with hypouricemic therapy.

Colchicine Mechanism of Action

Colchicine acts as an anti-inflammatory agent.
It interferes with neutrophil functions, including chemotaxis and phagocytosis.
Colchicine inhibits phospholipase A2, which lowers inflammatory prostaglandins and leukotrienes.

Colchicine Pharmacokinetics

Colchicine is not protein-bound.
It's highly lipid-soluble and readily crosses tissues.
The half-life is about 4 hours after oral administration.
Colchicine can be detected in neutrophils for up to 10 days after a single dose.
It's primarily metabolized in the liver and excreted in bile with about 20% excreted unchanged in urine.

Colchicine Indications

Treatment of acute gouty attacks.
Prophylaxis against future attacks, especially when initiating hypouricemic therapy.
Treatment of other inflammatory arthropathies (e.g., familial Mediterranean fever, pseudogout, acute sarcoid arthritis).

Colchicine Dosages

Colchicine is available as 0.5-0.6 mg tablets.
Prophylactic dose: 0.6 mg once or twice daily (reduces frequency in up to 85% of patients with normal renal function), usually until symptoms are resolved.
Acute attacks: 1.2 mg initial dose, followed by 0.6 mg one hour later; provides similar efficacy to higher dose regimens with less toxicity.

Colchicine Precautions

Reduce dose or avoid in patients with severe renal or hepatic insufficiency.
Avoid in patients taking CYP3A4 inhibitors.
Cautious use in patients on cyclosporine (risk of neuromyopathy). Tacrolimus is less problematic.

Colchicine Toxicity

Most side effects are dose and duration-related and worsen with chronic use and renal insufficiency.
No antidotes for overdose, and hemodialysis is ineffective.
Potential side effects include GI effects, bone marrow suppression, neuromyopathy, alopecia, and reproductive issues.

Uric Acid-Lowering Therapy (Antihyperuricemic)

Uricosurics (probenecid): enhance renal excretion of uric acid.
Xanthine oxidase inhibitors (allopurinol, febuxostat): inhibit uric acid synthesis.
Uricase (pegloticase): converts uric acid to allantoin.

Uric Acid-Lowering Therapy (Initiation)

Should be initiated only after an acute gout attack has resolved.
The risk of recurrence is minimized by gradual increases and prophylaxis using colchicine, NSAIDs, or low-dose prednisone.

Uricosuric Therapy (Mechanism)

Inhibit URAT1 and GLUT9 to decrease tubular reabsorption of uric acid.
Works best with increased urine alkalinity (pH >6.0) and flow (>1500 mL/day).

Uricosuric Therapy (Probenecid)

Generally well-tolerated (>90% of patients).
Should not be stopped during an acute gout attack.
Half-life: 6-12 hours, hepatically metabolized.
Forms: 500 mg tablets, sometimes combined with 0.5 mg colchicine.
Dosage: Initial dose 500 mg twice daily, gradually increased to 3 g daily (average 1 g/day in divided doses).

Uricosuric Therapy (Drug Interactions)

Probenecid prolongs the half-life of penicillin, dapsone, methotrexate, indomethacin, and others by decreasing their renal excretion.
It also prolongs heparin metabolism.

Xanthine Oxidase Inhibitors (Indications)

Urate overproduction (uric acid >800 mg/24 hr urine).
Nephrolithiasis
Renal insufficiency (CrCl < 50 mL/min).
Tophi (may take months to resolve).
Failure or intolerance of uricosuric agents.
Other indications include hyperuricemia with nephrolithiasis, tumor lysis syndrome prophylaxis, HPRT deficiency (Lesch-Nyhan syndrome), myeloproliferative disorders, serum urate >12.0 mg/dL, or 24-hour urine uric acid >1100 mg.

Xanthine Oxidase Inhibitors (Febuxostat/Allopurinol - Mechanism/PK)

Febuxostat/Allopurinol mechanism of action involves inhibiting xanthine oxidase which leads to more xanthine and hypoxanthine.
Febuxostat is absorbed in the GIT at 50%, metabolized by the liver, and excreted through the liver and kidneys.
Allopurinol is metabolized to oxipurinol by xanthine oxidase and has a long half-life (14-28 hrs.).

Xanthine Oxidase Inhibitors (Febuxostat/Allopurinol- Dosages/Toxicity)

Febuxostat is given at 40-mg/80-mg once daily and can be increased to 80-120mg/day.
Allopurinol is given at 100-mg/300-mg daily and can be increased to 4 mg/kg.
Allopurinol side effects include a maculopapular rash (3% risk), diarrhea, abnormal liver function enzymes.
Allopurinol hypersensitivity syndrome (AHS) is less common but can be severe, presenting with skin rash, fever, eosinophilia, hepatic necrosis, leukocytosis, and worsening renal function within 2-4 weeks of starting treatment. AHS occurs in 0.1% to 0.4% of patients. Use of desensitization protocols is no longer recommended.

Pegloticase Mechanism/Administration/Precautions

Pegloticase is a recombinant mammalian uricase attached to polyethylene glycol (PEG).
It's used for severe or refractory gout when other treatments fail to lower serum uric acid to <6 mg/dL.
Given as a 2-hour IV infusion of 8 mg every 2 weeks
All patients must be screened for G6PD deficiency before use. Avoid in patients with low G6PD activity.
Monitor serum uric acid levels before each infusion to assess efficacy and to avoid antibody-mediated reactions, including anaphylaxis.
Initiate prophylaxis (colchicine, NSAIDs, or prednisone) one week before pegloticase initiation.

Renal Handling of Uric Acid

Uric acid is excreted primarily (66%) through the kidneys via glomerular filtration, proximal tubule reabsorption, and tubular secretion and reabsorption.
In renal failure, GI excretion increases.

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Description

Test your knowledge on colchicine's role in treating gout, including its anti-inflammatory effects, recommended dosages, and potential drug interactions. This quiz covers essential information about the use of colchicine in clinical practice and its effects on patient care.