37. Non-steroidal antiinflammatory drugs: Drugs other than aspirin or paracetamol. Drugs used to treat gout.

Page created on June 13, 2019. Last updated on January 7, 2022 at 22:08

Other NSAIDs

The analgetic and antiinflammatory effects of different NSAIDs are very similar. Some patients respond better to some NSAIDs than others.

NSAIDSpecial featuresSpecial indications
NaproxenLess cardiovascular risk, strong plasma protein binding
IbuprofenLess GI, renal, cardiovascular (?) side effect risk, strong plasma protein binding
DiclofenacAccumulates in synovial fluid, higher cardiovascular riskRheumatoid arthritis
IndomethacinInhibits phagocytosis of urate crystalsGout
COX2-preferential and COX2-specific NSAIDs

Compounds:

  • COX2-preferential
    • Celexocib
    • Paracetamol
    • Meloxicam
  • COX2-specific
    • Parecoxib
    • Etoricoxib

These drugs have an important benefit over traditional NSAIDs; they cause minimal gastrointestinal side effects.

Dosing:

All orally, except parecoxib which is IV.

Indications:

  • Same as for non-selective NSAIDs, but preferred in people with:
    • Peptic ulcer
    • Platelet disorders
    • Aspirin asthma
  • Unique indications
    • Prevention of colorectal cancer in famillial adenomatous polyposis

Contraindications:

  • Sulpha drug allergy

These drugs are sulpha drugs, so they should be used carefully in people with allergy to other sulpha drugs.

Side effects:

  • No antiplatelet effect
  • Minimal GI side effects
  • No aspirin asthma
  • Same as for non-selective NSAIDs:
    • Decreased renal function
    • Cardiovascular side effects

It was previously believed that COX2-selective NSAIDs produced more cardiovascular side effects than the non-selective ones, but recently that has been disproved. Both types cause similar risk for cardiovascular side effects.

Drugs used to treat gout

Gout is a condition caused by precipitation of sodium urate crystals in soft tissue, joints and kidneys. It’s always related to an increase in uric acid (urate) levels in the body, either due to a primary genetic defect in uric acid secretion or due to any other condition that causes accumulation of uric acid, like:

  • Massive cell destruction – as cells release purine nucleotides that are metabolised into uric acid
    • Often during chemotherapy of malignant tumors
  • Reduced excretion of uric acid
    • Renal failure
    • Thiazide or loop diuretics
  • Ethanol

Xanthine oxidase is the most important enzyme in this disease, as it’s involved in the breakdown of xanthine and hypoxanthine into uric acid. Hypoxanthine and xanthine are water-soluble, but uric acid is not.

Treatment:

Treatment involves diet low in purines, abstinence from alcohol and adequate fluid intake. Pharmacological treatment involves:

  • Uricostatic agents – drugs that reduce the formation of uric acid
    • Allopurinol
    • Febuxostat
  • Uricolytic agents – drugs that cleave uric acid
    • Rasburicase
  • Uricosuric agents – drugs that reduce renal reabsorption of uric acid
    • Probenecid
    • Lesinurad

Arthritic attacks are treated with anti-inflammatory drugs like NSAIDs, colchicine and glucocorticoids.

Uricostatic drugs

Allopurinol and febuxostat are the important uricostatic drugs. The former is the first choice.

During the first few weeks NSAIDs should be co-administered to prevent gouty attacks.

Indications:

Prophylaxis for gout. Febuxostat is used in cases where allopurinol is not tolerated.

Mechanism of action:

Allopurinol is a competitive inhibitor for xanthine oxidase. It’s broken down into oxipurinol, which non-competitively inhibits the same enzyme.

Febuxostat is a non-competitive inhibitor for xanthine oxidase.

These drugs reduce the production of uric acid and cause hypoxanthine and xanthine to accumulate instead. These compounds are water-soluble and will be excreted by the kidney.

Interactions:

These drugs decrease the metabolism of azathioprine and mercaptopurine, as these are broken down by xanthine oxidase.

Side effects:

Gastrointestinal disturbances.

These drugs may precipitate a gouty attack in the first weeks of treatment. Co-administering NSAIDs or colchicine can prevent this.

Uricolytic drugs

The only important uricolytic drug is rasburicase. During the first few weeks NSAIDs should be co-administered to prevent gouty attacks.

Indications:

Prophylaxis for gout. Used in treatment-resistant cases of gout.

Mechanism of action:

Rasburicase is a recombinant form of urate oxidase, an enzyme that breaks down uric acid into water-soluble compounds like allantoin.

Dosing:

Intravenous infusion.

Side effects:

Allergic reactions. This drug may precipitate a gouty attack in the first weeks of treatment. Co-administering NSAIDs or colchicine can prevent this.

Uricosuric drugs

The most important drugs here are probenecid and lesinurad. During the first few weeks NSAIDs should be co-administered to prevent gouty attacks.

Indications:

Prophylaxis for gout.

Mechanism of action:

These drugs inhibit the transporter URAT1 in the proximal tubule, which preforms reabsorption of uric acid. This causes less uric acid to be reabsorbed and more to be excreted.

Side effects:

The increased excretion of uric acid may increase the risk of urate urolithiasis. This can be prevented by increasing fluid intake.

These drugs may precipitate a gouty attack in the first weeks of treatment. Co-administering NSAIDs or colchicine can prevent this.

Colchicine

NSAIDs are preferred over colchicine to treat acute gouty attacks because they have less side effects.

Indications:

Acute gouty attacks.

Mechanism of action:

Colchicine inhibits the polymerization of tubulin into microtubules, which reduces the chemotaxis and phagocytic activity of neutrophils. It also inhibits some functions of T cells.

This decreases the inflammatory response seen during gouty attacks.

Dosing:

Oral or IV.

Contraindications:

Should be used with care in people with liver or renal failure.

Side effects:

Gastroenteritis, myopathy, teratogenicity.


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