Allopurinol Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R25:Giftig beim Verschlucken.
R43:Sensibilisierung durch Hautkontakt möglich.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S28:Bei Berührung mit der Haut sofort abwaschen mit viel . . . (vom Hersteller anzugeben).
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S24:Berührung mit der Haut vermeiden.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Chemische Eigenschaften
White to Off-White Solid
Verwenden
Allopurinol does not reduce serum uric acid levels by increasing renal uric acid excretion; instead it lowers plasma urate levels by inhibiting the final steps in uric acid biosynthesis.
Uric acid in humans is formed primarily by xanthine oxidase-catalyzed oxidation of hypoxanthine and xanthine to uric acid. Allopurinol (8) and its primary metabolite, alloxanthine (9) [CAS: 2465-59-0], are inhibitors of xanthine oxidase. Inhibition of the last two steps in uric acid biosynthesis by blocking xanthine oxidase reduces the plasma concentration and urinary excretion of uric acid and increases the plasma levels and renal excretion of the more soluble oxypurine precursors. Normally, in humans the urinary purine content is almost solely uric acid; treatment with allopurinol results in the urinary excretion of hypoxanthine, xanthine, and uric acid, each with its independent solubility. Lowering the uric acid concentration in plasma below its limit of solubility facilitates the dissolution of uric acid deposits. The effectiveness of allopurinol in the treatment of gout and hyperuricemia that results from hematogical disorders and antineoplastic therapy has been demonstrated.
Indications
Allopurinol (Zyloprim) is the drug of choice in the treatment
of chronic tophaceous gout and is especially useful
in patients whose treatment is complicated by renal insufficiency.
Allgemeine Beschreibung
Odorless tasteless white microcrystalline powder.
Air & Water Reaktionen
Insoluble in water.
Reaktivität anzeigen
Allopurinol is an aminoalcohol. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Allopurinol darkens above 572° F, and at an indefinite high temperature, Allopurinol chars and decomposes. At 221° F, maximum stability occurs at pH 3.1- 3.4. Allopurinol decomposes in acidic and basic solutions.
Brandgefahr
Flash point data for Allopurinol are not available; however, Allopurinol is probably combustible.
Mechanism of action
Allopurinol, in contrast to the uricosuric drugs, reduces
serum urate levels through a competitive inhibition of
uric acid synthesis rather than by impairing renal urate
reabsorption. This action is accomplished by inhibiting
xanthine oxidase, the enzyme involved in the metabolism
of hypoxanthine and xanthine to uric acid. After
enzyme inhibition, the urinary and blood concentrations
of uric acid are greatly reduced and there is a simultaneous
increase in the excretion of the more soluble
uric acid precursors, xanthine and hypoxanthine.
Allopurinol itself is metabolized by xanthine oxidase
to form the active metabolite oxypurinol, which
tends to accumulate after chronic administration of the
parent drug.This phenomenon contributes to the therapeutic
effectiveness of allopurinol in long-term use.
Oxypurinol is probably responsible for the antigout effects
of allopurinol. Oxypurinol itself is not administered
because it is not well absorbed orally.
Pharmakokinetik
Allopurinol was synthesized in 1956 as part of a study of purine antagonists. It is well absorbed on oral
administration, with peak plasma concentrations appearing within 1 hour. Decreases of uric acid can be observed
within 24 to 48 hours. Excretion of allopurinol and its metabolite occurs primarily in the urine, with approximately 20%
of a dose being excreted in the feces.
Clinical Use
Allopurinol is especially indicated in the treatment of
chronic tophaceous gout, since patients receiving it show
a pronounced decrease in their serum and urinary uric
acid levels. Because it does not depend on renal mechanisms
for its efficacy, allopurinol is particularly beneficial
for patients who already have developed renal uric acid
stones, patients with excessively high urate excretion
(e.g., above 1,200 mg in 24 hours), patients with a variety
of blood disorders (e.g., leukemia, polycythemia vera),
patients with excessive tophus deposition, and patients
who fail to respond well to the uricosuric drugs.
Allopurinol also inhibits reperfusion injury. This injury
occurs when organs that either have been transplanted
or have had their usual blood perfusion blocked
are reperfused with blood or an appropriate buffer solution.
The cause of this injury is local formation of free
radicals, such as the superoxide anion, the hydroxyl free
radical, or peroxynitrite. These substances are strong
oxidants and are quite damaging to tissues.
Nebenwirkungen
Common toxicities associated with allopurinol administration
include a variety of skin rashes, gastrointestinal
upset, hepatotoxicity, and fever. These reactions are often
sufficiently severe to dictate termination of drug
therapy. It is advised that therapy not be initiated during
an acute attack of gouty arthritis. As with the uricosuric
drugs, therapy with allopurinol should be accompanied
both by a sufficient increase in fluid intake to
ensure water diuresis and by alkalinization of the urine.
Prophylactic use of colchicine also helps to prevent
acute attacks of gout that may be brought on during the
initial period of allopurinol ingestion.
Sicherheitsprofil
Human poison by
ingestion. Poison experimentally by
intraperitoneal and subcutaneous routes. An
experimental teratogen. Human systemic
effects by ingestion: blood leukopenia,
dermatitis, jaundice, muscle weakness,
thrombocytopenia. When heated to
decomposition it emits toxic fumes of NOx.
An FDA proprietary drug used as a xanthine
oxidase inhibitor.
Stoffwechsel
Allopurinol is rapidly metabolized via oxidation and the formation of numerous ribonucleoside derivatives. The major oxidation metabolite, alloxanthine or oxypurinol, has a much longer half-life
(18–30 hours versus 2–3 hours) than the parent drug and is an effective, although less potent, inhibitor of xanthine
oxidase. The longer plasma half-life of alloxanthine results in an accumulation in the body during chronic
administration, thus contributing significantly to the overall therapeutic effects of allopurinol.
Vorsichtsmaßnahmen
Since allopurinol is metabolized by the hepatic microsomaldrug-metabolizing enzymes, coadministration ofdrugs also metabolized by this system should be donewith caution. Because allopurinol inhibits the oxidationof mercaptopurine and azathioprine, their individualadministered doses must be decreased by as much as75% when they are given together with allopurinol.Allopurinol may also increase the toxicity of other cytotoxicdrugs (e.g., vidarabine). The actions of allopurinolare not antagonized by the coadministration of salicylates.
Allopurinol Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
