Allopurinol

Allopurinolum

For medical students2 min readUpdated 2026-10-10

Allopurinol is an oral medication used for the prophylaxis of gout attacks. It works by inhibiting a key enzyme of purine metabolism and reducing uric acid synthesis.

Chemical structureStructural analogue of hypoxanthine

Molecular targetEnzyme xanthine oxidase

Route of administrationOral

Clinical effectProphylaxis of gout attacks

Chemical Structure and Biochemical Target

Chemically, allopurinol is a structural analogue of hypoxanthine, a natural precursor of uric acid in the human body. The primary biochemical target for this drug is the enzyme xanthine oxidase, which regulates key steps in purine metabolism.

Mechanism of Pharmacological Action

Under normal conditions, the biochemical pathway proceeds as follows: hypoxanthine is converted by xanthine oxidase into xanthine, which is then oxidized by the same enzyme into the final product, uric acid.

Due to its marked structural similarity to the natural substrate, allopurinol performs competitive inhibition of xanthine oxidase. As a result, the sequential reactions of uric acid formation are blocked, leading to the following changes:

Slowed synthesis of uric acid.
Decreased concentration of uric acid in body fluids.
Increased levels of hypoxanthine and xanthine in blood plasma.

Safety Rationale and Medical Application

An important advantage of this pharmacological maneuver is its safety profile. Unlike excess uric acid, the accumulating intermediate products—hypoxanthine and xanthine—have excellent solubility in plasma. They do not precipitate or form hard crystals or stones in tissues.

In clinical practice, the drug is administered exclusively orally and is used by physicians as a reliable agent for the prophylaxis of gout attacks.

Mnemonic

Allopurinol is a hypoxanthine analogue: blocks xanthine oxidase, eliminates uric acid, leaving soluble safe precursors.

Frequently asked questions

To which pharmacological group of anti-gout agents does allopurinol belong?

Allopurinol belongs to the pharmacological group of urate-lowering agents (uricosuric-suppressive drugs), which are xanthine oxidase inhibitors. The primary goal of using drugs in this group is to lower plasma uric acid levels by suppressing its synthesis. This is necessary to prevent recurrent attacks of the disease and tophi formation. Allopurinol is the first-line drug for baseline (urate-lowering) therapy of gout.

What are the main adverse effects associated with allopurinol?

Allopurinol is associated with a wide range of adverse effects affecting various systems:

Paradoxical flare — risk of triggering an acute gout attack in the first weeks of therapy.
Allergic reactions — dermatitis, pruritus, urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Lyell syndrome).
Hematologic system — agranulocytosis, anemia, thrombocytopenia, eosinophilia, leukopenia.
Renal system — acute kidney injury, interstitial nephritis.
Nervous system — somnolence, headache, dizziness, asthenia.
Musculoskeletal system — myopathy, myalgia, arthralgia.
Gastrointestinal tract — dyspepsia (diarrhea).

Is it appropriate to use allopurinol to treat an acute gout attack?

It is inappropriate to use allopurinol to treat an acute gout attack. The drug is not used for immediate treatment and analgesia in the acute phase; an acute gout attack is listed among the contraindications for initiating allopurinol. Allopurinol is used as baseline urate-lowering therapy to prevent gout attacks, including during the intercritical period. During an acute attack, adjustments to urate-lowering drug therapy should be avoided, as sudden fluctuations in urate levels can exacerbate the attack.

Which immunosuppressants and antineoplastic agents have clinically significant interactions with allopurinol?

Allopurinol has clinically significant interactions with the following drugs:

Mercaptopurine — an antineoplastic agent. Allopurinol inhibits xanthine oxidase, thereby slowing the metabolism of mercaptopurine. This leads to a sharp increase in its toxicity (bone marrow suppression); therefore, the dose of mercaptopurine must be reduced by 75%.
Azathioprine (Azathioprine) — an immunosuppressant. Allopurinol inhibits the metabolism of its active metabolites, resulting in enhanced and prolonged effects of azathioprine with a high risk of toxicity.

What is the primary mechanism of action of allopurinol?

Due to its structural similarity to hypoxanthine, the drug competitively inhibits the enzyme xanthine oxidase, thereby blocking the formation of uric acid.

Why is the accumulation of hypoxanthine and xanthine safe for the body?

Unlike uric acid, these intermediate compounds are highly soluble in plasma and do not form crystals or stones.

What is the main clinical goal of prescribing allopurinol?

The drug is administered orally for the prophylaxis of gout attacks.

Go deeper

Variants of structural precursors of uric acid (adenine, guanine, xanthine, hypoxanthine)
Detailed biochemical cascade of purine oxidation
Kinetics of competitive xanthine oxidase inhibition
Physicochemical properties of hypoxanthine and xanthine in blood plasma
Features of oral administration of the drug in gout