Pharmacology - An Illustrated Review

33. Analgesic, Antipyretic, and Antiinflammatory Drugs

Inflammation is usually the result of a noxious stimulus that results in the destruction of or injury to tissue. Inflammation functions to remove noxious agents from the site of injury, to repair damage, and to return tissue function to normal. The clinical features of inflammation are swelling, redness, heat, and pain.

Inflammatory mediators

Cytokines, which are secreted primarily by activated macrophages, are important mediators of inflammation. The most i mportant inflammatory mediators are interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Local effects include induction of adhesion molecule expression on vascular endothelium (promoting cell adherence), increased vascular permeability (promoting influx of serum components), and activation of lymphocytes. Systemic effects include increased leukocyte production, fever, and induction of acute phase response. Other important cytokines include interleukin-8 (IL-8), a potent chemotactic factor for recruitment of neutrophils, basophils, and T cells, and interleukin-12 (IL-12), which activates NK cells and promotes differentiation of T cells into T helper (TH) cells.


33.1 Nonsteroidal Antiinflammatory Drugs

Nonsteroidal antiinflammatory drugs (NSAIDs) are analgesic, antipyretic, and antiinflammatory drugs, thus named to distinguish them from the glucocorticosteroids, which also possess anti-inflammatory properties. This class of drugs includes some commonly used over-the-counter agents, as well as many prescription-only agents.

Mechanism of action

– Antiinflammatory: NSAIDs inhibit the cyclooxygenase enzymes COX-1 and COX-2 (Fig. 33.1). These enzymes catalyze the formation of prostaglandin H2, which is the precursor for prostaglandin, prostacyclin, and thromboxane synthesis. COX-1 is present in most tissues, and in the gastrointestinal (GI) tract it maintains the normal lining of the stomach. It is also involved in kidney and platelet function. COX-2 is induced by inflammation. COX-2 inhibition is thought to lead to the analgesic, antipyretic, and antiinflammatory effects of aspirin and the other NSAIDs.

— Aspirin inhibits the cyclooxygenase enzymes by acetylating a single serine residue. This is an irreversible covalent modification that inactivates both COX-1 and COX-2. Other NSAIDs are competitive inhibitors of the cyclooxygenases.

– Analgesic: NSAID analgesic effects occur as a result of decreased prostaglandin formation.

– Antipyretic: Antipyretic effects are the result of decreasing prostaglandins in the temperature control center in the hypothalamus.

Set point temperature and temperature regulation

The preoptic region and adjacent anterior nuclei of the hypothalamus contain a thermostat for establishing the set point temperature. The set point temperature (~37°C) is the body core temperature that the system attempts to maintain. If core temperature falls below the set point, then the following mechanisms may be induced by the posterior hypothalamus: somatic nervous system activation induces shivering generating heat by causing ATP hydrolysis in the contractile apparatus of skeletal muscle; thyroid hormones may be released generating heat by increasing the activity of Na+-K+–ATPase; and sympathetic nervous system activation causes vasoconstriction of blood vessels to the skin resulting in heat conservation. If core temperature rises above the set point, then the following mechanisms may be induced by the anterior hypothalamus: sympathetic cholinergic activation of sweat glands (via muscarinic receptors) increases heat loss by evaporation of water from the skin; and lowered sympathetic adrenergic activity causes dilation of blood vessels to the skin resulting in heat loss by convection and radiation.


Fever and antipyretic drugs

Fever is produced by endogenous pyrogens (e.g., interleukin-1) released by infective bacteria. These pyrogens act on the anterior hypothalamus to increase prostaglandin synthesis, which in turn stimulates the thermoregulatory center to reset the new set point to a higher temperature. Because body temperature is cooler than the new set point, body temperature increases (heat production and conservation of heat) until it stabilizes at the new, elevated set point temperature. After the fever breaks and the new set point returns to 37°C, the patient vasodilates and sweats to lose heat until body temperature returns to normal. Aspirin (and other NSAIDs) and acetaminophen are effective in suppressing fever because they inhibit cyclooxygenase and therefore prostaglandin synthesis. In doing so, they lower the set point temperature and will cause activation of the heat loss mechanisms. Steroids may also be used to reduce fever by blocking the release of arachidonic acid (the precursor of prostaglandins) from membrane phospholipids.



– Mild to moderate pain (e.g., dental, muscle, joint, and postoperative)

– Inflammation and accompanying pain associated with diseases, such as rheumatoid arthritis (high doses)

– Reduction of fever

– Aspirin is also used for the treatment and prophylaxis of thrombosis (low doses). It is widely used to prevent myocardial infarction (MI), stroke, and peripheral vascular thrombosis. It is also used after angioplasty, placement of stents, or bypass surgery to prevent thrombosis and re-stenosis.

Side effects. Many of the adverse effects of aspirin and the other NSAIDs result from inhibition of COX-1 (Fig. 33.2). These include

– Acute renal failure

– Skin rash or hypersensitivity reactions, which require immediate discontinuation of the drug

– Gastric distress, occult gastric bleeding, and acute hemorrhage. These effects may be worsened with concomitant use of ethanol and selective serotonin reuptake inhibitors (SSRIs).

– Bronchospasm in NSAID-sensitive asthmatics (see p. 249)

Fig. 33.1 image Nonsteroidal antiinflammatory drugs (NSAIDs).

NSAIDs inhibit prostaglandin metabolism by inhibiting both forms of the enzyme cyclooxygenase (COX-1 and COX-2). Cyclooxygenase catalyzes the formation of prostaglandin H2 which is the most important step in prostaglandin production. The normal physiological effects of COX-1 and COX-2 are shown. Because NSAIDs block these actions, they have an antiinflammatory effect (wanted), but they also block the physiological effects of COX-1, which are the main cause of NSAID side effects. Glucocorticoids also inhibit prostaglandin (and leukotriene) production by inhibiting phospholipase A2 and COX-2 (indirectly).


Fig. 33.2 image Adverse effects of NSAIDs.

NSAID-induced inhibition of COX enzymes leads to decreased production of prostaglandins from arachidonic acid. This leads to gastric mucosal damage and its sequelae and nephropathy. COX-2 inhibitors show a lower incidence of gastropathy. Inhibition of this side of the arachidonic acid metabolic pathway may lead to increased leukotriene production, depending on arachidonic acid availability. This proinflammatory mediator can cause asthma and bronchoconstriction.



– Gastric ulcers (gastric irritation may aggravate ulcers)

– Asthma (NSAIDs can induce bronchospasm in asthmatics)

– Influenza-like illnesses in children or teenagers (up to 19 years of age). There is an increased risk of developing Reye syndrome in children with influenza or chickenpox.

– Pregnancy (third trimester). NSAIDs may cause premature closure of the ductus arteriosu s.

The relative strength of the antiinflammatory, analgesic, and antipyretic actions varies slightly among different NSAID agents. The major difference is in pharmacokinetics. Individual patients may show different therapeutic responses and adverse reactions to the different agents. The unique features of specific NSAID agents are discussed in the following section.


Aspirin (Acetylsalicylic Acid)


– Well absorbed following oral administration

– Rapidly metabolized by plasma esterases to salicylic acid and acetic acid

– Salicylate ion is highly bound (80–90%) to plasma proteins

– Conjugation in the liver is the primary route of metabolism.

– Metabolites are excreted in the urine.


– Cardiovascular system: at low doses, aspirin inhibits platelet COX-1 and prevents thrombosis. Aspirin does not affect blood pressure.

– Blood: increased bleeding time due to inhibition of platelet aggregation

– Kidney: no nephrotoxicity

– Liver: there may be dose-dependent alterations in liver function with salicylate use. These changes usually are subclinical and reversible.


– Influenza-like illnesses or chickenpox in children or teenagers (up to 19 years of age), as there is an increased risk of developing Reye syndrome.

– Asthma and nasal polyps, as there is an increased likelihood of hypersensitivity reaction

– Bleeding disorders such as hemophilia, as aspirin may increase bleeding

– Alcohol use (three or more drinks/day) or peptic ulcer, as there is an increased risk of GI bleeding

– Decreased hepatic function


– Acute toxicity may occur in children and teenagers (Reye syndrome) and is life-threatenin g.

– Overdose progressively leads to tinnitus, hyperventilation, respiratory alkalosis, fever, metabolic acidosis, shock, coma, and death. Treatment is gastric lavage for acute cases, alkaline diuresis with sodium bicarbonate to increase excretion, and supportive measures.

Reye syndrome

Reye syndrome is a rare disorder that affects all organs of the body, but liver and brain involvement is the most serious. It initially presents following a viral infection. Signs and symptoms progress from vomiting, lethargy, hyperventilation, and confusion to severe mental state changes, coma, respiratory failure, multiple organ failure, and death. Treatment is supportive and includes mechanical ventilation (if necessary), insulin (to increase glucose metabolism), corticosteroids (to reduce brain swelling), and diuretics (to increase fluid loss).


Salicylic Acid Salts and Derivatives

Mesalamine, Olsalazine, and Sulfasalazine

Mechanism of action. These agents do not irreversibly inhibit COX enzymes and are much less effective than aspirin as COX inhibitors. They also do not inhibit platelet aggregation.

Pharmacokinetics. These agents are taken orally or rectally.


– Ulcerative colitis (local effect on the GI tract)

– Crohn disease

– Rheumatoid arthritis (sulfasalazine)

Side effects

– Less frequent and minor compared with aspirin

Other Salicylates

Choline Magnesium Salicylate, Salsalate, and Diflunisal

Salsalate is the salicylate ester of salicylic acid; in vivo, the drug is hydrolyzed to two molecules of salicylate.

Diflunisal is a salicylic acid derivative but is not metabolized to salicylate.


– Given orally but also found in over-the-counter creams, gels, and patches for topical use


– Treatment of fever, pain, and arthritis in patients who cannot tolerate or are unresponsive to aspirin or other NSAIDs

Acetic Acids


Mechanism of action. Similar to aspirin.


– Indomethacin has been the agent of choice for gout; however, there is no evidence it is superior to other NSAIDs for acute gout.

– To accelerate closure of patent ductus arteriosus (see p. 349)

Side effects. A very high percentage (35−50%) of patients receiving usual therapeutic doses of indomethacin experience untoward symptoms, and ~20% must discontinue its use because of the side effects.

– The most frequent central nervous system (CNS) effect (indeed, the most common side effect) is severe frontal headache, occurring in 25 to 50% of patients who take the drug for long periods. Dizziness, vertigo, lightheadedness, and mental confusion may occur. Seizures have been reported, as have severe depression, psychosis, hallucinations, and suicide.

– GI complaints are common and can be serious. Diarrhea may occur and sometimes is associated with ulcerative lesions of the bowel. Acute pancreatitis has been reported, as have rare but potentially fatal cases of hepatitis.

– Neutropenia, thrombocytopenia, and, rarely, aplastic anemia

Note: Most adverse effects are dose-related.


Thrombocytopenia is a condition in which the platelet count is low. It can be caused by the decreased production of platelets, such as in bone marrow failure, and from the destruction or consumption of platelets, for example, in disseminated intravascular coagulation (DIC), hypersplenism, and viral infections, and from drugs (e.g., indomethacin). There may be no signs and symptoms of thrombocytopenia, and it may be diagnosed incidentally when the patient's blood count is measured, or there may be signs such as spontaneous bleeding from mucous membranes (e.g., gums and nose), easy and excessive bruising, and petichiae (superficial bleeding into the skin). The underlying cause should be treated if necessary.



– Underlying peptic ulcer disease

Note: Caution is advised when administering indomethacin to elderly patients or to those with underlying epilepsy, psychiatric disorders, or Parkinson disease because they are at greater risk for the development of serious CNS adverse effects.

Table 33.1 summarizes other NSAIDs.

  Table 33.1 image Summary of Other NSAIDs




Diclofenac, etodolac, ketorolac, sulindac, tolmetin

These NSAIDs have greater potency against COX-2, have some COX-2 selectivity, and have less antiinflammatory activity than other NSAIDs


They are similar to indomethacin


Ibuprofen, fenoprofen, flurbiprofen, ketoprofen, naproxen, oxaprozin

Propionic acid derivatives that differ mainly in pharmacokinetics.


Piroxicam, meloxicam

Major advantage is long duration of action



Unique structure but similar activity to other NSAIDs


COX-2 Selective Inhibitor


Mechanism of action. Celecoxib is a selective COX-2 inhibitor and as such inhibits the production of vascular prostaglandins, which are inhibitors of platelet aggregation and vasodilators. Unlike the nonselective NSAIDS, which inhibit both COX-1 and COX-2, celecoxib does not reduce the endogenous production of thromboxane A2, a potent activator of platelet aggregation and a vasoconstrictor. Thus inhibition of prostacyclin without inhibition of thromboxane A2 creates a prothrombotic state. However, the fact that it does not inhibit COX-1 leads to fewer GI side effects because it does not inhibit prostaglandins in the GI tract which maintain the normal lining of the stomach.

Side effects. Adverse cardiovascular and cerebrovascular events are more likely due to the prothrombotic state.

Note: Rofecoxib and valdecoxib have been withdrawn from the market because of the increased risk of cardiovascular events. Although celecoxib also carries such risks, it remains available, and its benefits (i.e., the reduced GI side effects) may outweigh the risks in properly selected and informed patients.

33.2 Other Analgesic-Antipyretic Drugs

Acetaminophen is excluded from the NSAID group of drugs because it does not have significant antiinflammatory activity, although it is analgesic and antipyretic.


Mechanism of action. Acetaminophen is a weak inhibitor of cyclooxygenases. Its mechanism of action is not well understood.


– Well absorbed following oral administration

– The primary route of metabolism is conjugation in the liver.

– Elimination is by filtration and active proximal tubular secretion into the urine.


– Antipyretic effects: comparable to aspirin

– Analgesic effects: comparable to aspirin

– Cardiovascular system: no effects at therapeutic doses

– Respiratory system: no effects at therapeutic doses

– Blood: no antiplatelet effects

– Acetaminophen has no significant antiinflammatory properties, which may be accounted for by the fact that it has greater activity against CNS cyclooxygenases than those in the periphery.


– Mild to moderate pain and pyrexia in patients for whom aspirin is contraindicated

– Analgesic of choice in pregnancy

Note: Acetaminophen does not cause Reye syndrome and may be used in children.

Toxicity. Acetaminophen has a high therapeutic index, requiring ≥ 6 g to be ingested for toxicity to occur. Hepatotoxicity is the most serious toxic effect, which is caused by the accumulation of N-acetyl-p-benzo-quinone imine (NAPQI), a toxic compound produced in small amounts during the metabolism of acetaminophen. Normally, it is immediately detoxified in the liver by conjugation with glutathione. In cases of acetaminophen overdose, glutathione may be depleted, and NAPQI may accumulate and damage the liver. Concurrent ethanol use may worsen the hepatic effect. Treat with acetylcysteine, which both replenish glutathione stores and may conjugate directly with NAPQI by serving as a glutathione substitute (only effective within 10 to 24 hours of overdose).

33.3 Drugs Used in the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that is mainly characterized by inflammation of the synovium of joints, especially the small joints of the hands and feet. This causes all of the signs of inflammation: pain, swelling, stiffness, redness, and loss of function. The synovium thickens as the disease progresses, and inflammatory mediators erode bone and cartilage, causing deformation of the joints. There is also a systemic component to RA that is thought to be mainly due to vasculitis (inflammation of blood vessels). Weight loss, fever, and malaise are often present, and there may be cardiovascular and respiratory disease, as well as problems with the skin and eyes.

Pathogenesis of rheumatoid arthritis

In RA, the immune system pathologically reacts to insults on the body by trigger factors, which may be genetic, environmental, infection, or trauma. The initial noxious stimulus causes inflammation of synovial membranes. The antigens released in this process are taken up by antigen presenting cells, and this in turn, activates lymphocytes and macrophages. The macrophages release further proinflammatory mediators, including cytokines and TNFα. Cyto kines activate COX-2 and induce prostaglandin synthesis. This inflammatory response leads to a viscous circle of lymphocyte and macrophage activation. Synovial fibroblasts also proliferate during this time and release destructive enzymes. These enzymes are responsible for the characteristic inflamed pannus tissue of RA, which progressively invades joint cartilage and bone, cumulating in ankylosis and connective tissue scar formation. This causes loss of joint motion (Fig. 33.3).


Disease-modifying Antirheumatic Drugs

Disease-modifying antirheumatic drugs (DMARDs) are commonly used with NSAIDs for the treatment of RA (Fig. 33.3). Corticosteroids may be used in conjunction with these agents.


This agent is discussed in detail in Chapter 27.

Mechanism of action. Methotrexate is a folic acid analogue that competitively inhibits dihydrofolate reductase, the enzyme that normally converts folate to tetrahydrofolate. This is needed for purine and thymidine synthesis.

Note: The mechanism of action in RA is unknown.


Purines are a group of extremely biochemically significant organic compounds. The nucleic acids adenine and guanine, which comprise 50% of our DNA and RNA, are derived from purines, as well as several other important substances, for example, adenosine triphosphate (ATP), guanosine triphosphate (GTP), cyclic adenosine mono-phosphate (cAMP), the reduced form of nicotinamide adenine dinucleotide (NADH), and coenzyme A.



– Administered orally for the treatment of RA

– Fifty percent is bound to plasma proteins (displaced by salicylates, sulfonamides, etc.).

– Excreted unchanged in urine (caution in patients with renal damage)

Uses. Methotrexate is generally the DMARD of choice for the treatment of RA.

Side effects. Side effects include oral and GI ulceration, bone marrow depression (dose-limiting toxicity), hepatic damage, and renal damage.


Mechanism of action. The mechanism for RA is unknown.


– Administered alone (in mild cases) or in combination with other antiinflammatory agents

– Clinical improvement may require 3 to 6 months of therapy.

Fig. 33.3 image Rheumatoid arthritis.

Refer to call-out box on p. 355 for the pathogenesis of rheumatoid arthritis. NSAIDs (COX inhibitors) and glucocorticoids inhibit prostaglandin synthesis, which provides acute relief from the inflammatory symptoms. Disease-modifying agents slow disease progression. Methotrexate and leflunomide reduce purine and pyrimidine synthesis in lymphocytes, which prevents them from replicating (due to inhibition of DNA and RNA synthesis). Cyclosporine decreases interleukin-2 (IL-2) synthesis in T helper cells. The antibodies infliximab and adalimumab and the fusion protein etanercept intercept tumor necrosis factor-α (TNFα) molecules (which are proinflammatory cytokines) and prevent them from interacting with membrane receptors on target cells. Anakinra is an analog of endogenous IL-1 antagonists. The mechanism of action of sulfasalazine is unknown.


Side effects. Serious ocular toxicity is associated with this agent but is rare at doses used for RA.


Mechanism of action. Sulfasalazine is a prodrug that is metabolized to 5-aminosalicylate (5-ASA). 5-ASA acts within the intestinal tract (mainly the terminal ileum and colon) to inhibit prostaglandin and leukotriene synthesis, thus reducing the inflammatory reaction (see Chapter 27).

The mechanism of action of sulfasalazine in RA is unknown.


– Mild cases of RA

Side effects

– Nausea, vomiting, diarrhea, headache, and abdominal pain

– Bone marrow suppression

Gold Salts

Mechanism of action. Gold salts have antiinflammatory properties and inhibit prostaglandin synthesis. They have no analgesic or antipyretic effects.


– Used infrequently for the treatment of inflammatory conditions

– May induce remission of RA, but the duration is highly variable. The mechanism by which they induce remission is unknown.

Side effects

– Mucocutaneous lesions, blood dyscrasias, and anaphylactoid reactions

Blood dyscrasia

Blood dyscrasia is a general term for a pathologic disorder of the blood in which the cellular constituents of the blood are abnormal or are present in abnormal quantities. Examples of this include idiopathic thrombocytopenic purpura, hemophilia, sickle cell anemia, and leukemia.



Mechanism of action. Leflunomide is an inhibitor of pyrimidine synthesis. Its mechanism to relieve symptoms of RA is unclear, but it may inhibit the proliferation of T cells to reduce i nflammation.


– Orally effective


– I nitial monotherapy for RA instead of methotrexate, or added to methotrexate for patients who have not responded


– Reduces symptoms and improves function

Side effects

– Diarrhea occurs frequently.

– Reversible alopecia and skin rash are common.

– Hypertension

– Hepatotoxicity


– Pregnancy

Tumor Necrosis Factor-α (TNF-α) Inhibitors

These agents are also discussed in Chapter 34.

Etanercept, Infliximab, and Adalimumab

– Etanercept is a soluble recombinant TNF receptor: Fc fusion protein.

– Infliximab is a chimeric monoclonal antibody that binds to TNF-α.

– Adalimumab is a human monoclonal antibody to TNF.

Mechanism of action. These agents bind to TNF-α, a proinflammatory cytokine, and prevent it from attaching to its receptor (Fig. 33.4).


– Etanercept and adalimumab are administered subcutaneously.

– Infliximab requires IV administration.

Uses. Use of a TNF inhibitor concurrently with methotrexate is more effective for treating RA than either one alone. These drugs provide symptomatic relief in 60% of patients, but they are not curative.

Fig. 33.4 image TNF-α and inhibitors.

TNF-α receptor activation produces a number of effects that can worsen rheumatoid arthritis (RA). TNF levels are elevated in the synovial fluid of patients with RA. Infliximab is a chimeric monoclonal antibody to TNF-α. Etanercept is a soluble recombinant TNF receptor:Fc fusion protein. Both of these drugs bind to TNF-α and prevent it from interacting with its receptor. Adalimumab (not shown) is a human monoclonal antibody to TNF-α that works like infliximab.


Side effects

– Minor irritation at injection sites is the most common side effect of etanercept and adalimumab.

– Increased susceptibility to bacterial and fungal infections. Serious and fatal infections have occurred.

IL-1 Antagonist


Anakinra is a recombinant form of the human interleukin-1 receptor antagonist IL-1 Ra.

Mechanism of action. Anakinra blocks the actions of endogenous IL-1, thereby decreasing IL-1-mediated inflammatory responses. It has shown moderate effectiveness.


– Given by daily subcutaneous injection

Side effects. Side effects of anakinra are the same as TNF-α inhibitors: injection site reactions and increased susceptibility to infections.

33.4 Drugs Used in the Treatment of Gout

Gout is an arthropathy caused by hyperuricemia and the deposition of uric acid crystals in the joints. It may be precipitated by trauma, surgery, starvation, infection, or diuretic therapy. It often occurs in the metatarsophalangeal joint of the great toe (hallux). Symptoms include severe pain, redness, and swelling of the affected joints. The therapy of gout involves treatment of the acute attack with colchicine and NSAIDs, and chronic treatment of the hyperuricemia.

Treatment of Acute Gout


Mechanism of action. Colchicine inhibits mitotic activity, neutrophil migration, and phagocytic activity in inflamed tissue (Fig. 33.5).

Fig. 33.5 image Gout and its therapy.

Gout results from increased levels of uric acid (an end product of purine degradation). Uric acid tends to crystallize in the metatarsophalangeal joints and provides a strong stimulus for neutrophils and macrophages. Neutrophils are attracted (1) and phagocytose (2) the uric acid crystals. Neutrophils release proinflammatory cytokines (3). Macrophages also phagocytose the crystals and release lysosomal enzymes that promote inflammation. This results in an acute and very painful attack of gout (4). Colchicine and NSAIDs are used to treat acute attacks of gout. Colchicine binds to microtubular proteins and impairs their function, causing inter alia arrest of mitosis at metaphase (“spindle poison”). Its acute antigout activity is due to inhibition of neutrophil and macrophage reactions. Allopurinol is a uricostatic agent that, along with its accumulating metabolite, oxypurinol, inhibits xanthine oxidase, which catalyzes the formation of uric acid from hypoxanthine via xanthine. Uricosurics promote the renal excretion of uric acid by saturating the organic acid transport system in the renal proximal tubules, making it unavailable for uric acid resorption.


Side effects. GI irritation, bone marrow depression, myopathy, and alopecia with long-term use.

Indomethacin and Other NSAIDs

Indomethacin (p. 353) has been the traditional NSAID used for acute gout attacks, but there is no evidence that it is superior to other NSAIDS. Ibuprofen, naproxen, and celecoxib may be just as effective.

Treatment of Chronic Gout

Probenecid and Sulfinpyrazone

Mechanism of action. These agents block the proximal tubular reabsorption of uric acid.


– Rapidly absorbed orally

Side effects.

– GI irritation and allergic reactions

Contraindications. Aspirin can impair the excretion of uric acid from the kidneys at the usual over-the-counter doses; however, low-dose aspirin taken for heart attack or stroke prevention should not significantly alter the uric acid level.


Mechanism of action. Allopurinol reduces the synthesis of uric acid by inhibiting xanthine oxidase, which is the enzyme that catalyzes the formation of uric acid from hypoxanthine via xanthine.

Side effects. GI irritation, allergic reactions, and blood dyscrasias

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