Antihyperuricemics Medications

• Gout is an inflammatory disorder resulting from hyperuricemia, a condition marked by elevated uric acid levels in the blood.
• Hyperuricemia leads to the formation of urate acid crystals that deposit in small joints, particularly the big toe and can deposit in the skin and organs if left untreated.
• Uricosurics treat hyperuricemia that causes gout or that occurs from cancer chemotherapy and some blood dyscrasias.

Prototype and Other Medications

• Allopurinol is the prototype medication for antihyperuricemics.
• Other medications that treat hyperuricemia include febuxostat, probenecid, pegloticase, and rasburicase.
• Colchicine was previously used to treat hyperuricemia but has been replaced by newer medications with fewer adverse effects.
• Pegloticase treats chronic gout that doesn’t respond to allopurinol and probenecid.
• Rasburicase treats hyperuricemia in clients receiving anticancer therapy because chemotherapy causes tumor breakdown, leading to elevated uric acid levels.

Expected Pharmacologic Action

• Allopurinol and febuxostat inhibit xanthine oxidase (XO) from converting hypoxanthine and xanthine into uric acid.
• Probenecid inhibits tubular reabsorption of uric acid in the kidneys, promoting its excretion.

Adverse Drug Reactions

• Clients generally tolerate uricosurics well.
• Hypersensitivity syndrome can occur: fever, rash, eosinophilia, as well as liver and kidney dysfunction.
• Gastrointestinal disturbances are possible: nausea, vomiting, diarrhea.
• CNS effects: drowsiness, headache, and vertigo may occur.
• Bone marrow depression can result in agranulocytosis (decreased white blood cells), aplastic anemia (decreased blood cells), or thrombocytopenia (low platelet level).
• Some clients may report a metallic taste or develop cataracts after more than 3 years of use.

Interventions

• Monitor for hypersensitivity syndrome (fever or rash) when clients start taking a uricosuric or have been taking it for 2-4 weeks.
  • If fever or rash develops, stop the medication and check liver and kidney function tests, and notify the provider.
• For nausea and/or vomiting, give the medication after meals and ensure adequate hydration.
• Assist clients when ambulating to prevent falls if drowsiness or vertigo occurs.
• Give a mild analgesic for headaches.
• Monitor CBC for indications of bone marrow suppression, as well as liver and kidney function tests.
• Monitor uric acid levels to determine the effectiveness of the medication therapy.
• Acknowledge that a metallic taste is to be expected.
• Clients taking a uricosuric should see their ophthalmologist regularly to evaluate for the development of cataracts.

Administration

• Allopurinol can be administered orally or IV.
• Obtain a client’s baseline uric acid level and then monitor subsequent levels every 1 to 2 weeks until the appropriate dosage is determined.
• Obtain baseline CBC and liver and kidney function tests before therapy and monitor them periodically afterward for changes in these values.
• Allopurinol tablets can be crushed and mixed with food or fluid.
• Administer IV using recommended dilution and infuse over 30 to 60 minutes.
• Make sure clients drink at least 3 L of fluid per day when taking this medication.

Client Instructions

• Immediately report fever, rash, abdominal pain, swelling, or low urine output and stop taking the medication, these may indicate hypersensitivity syndrome
• Use over-the-counter analgesics as needed to relieve headaches.
• Avoid driving or doing activities that require mental alertness since allopurinol can cause drowsiness and vertigo.
• Report bleeding, easy bruising, or sore throat to the provider because of the potential for bone marrow suppression.
• Warn clients that they may develop a metallic taste in their mouth.
• Minimize eye exposure to sunlight by wearing sunglasses with ultraviolet (UV) protection.
• Teach clients the early manifestations of cataract development, including blurred vision and loss of color acuity.
• Obtain periodic eye examinations to monitor for the development of cataracts.
• Take the medication with food or right after a meal if it causes nausea.
• Throughout medication therapy, clients need to drink at least 3 L of fluid per day.

Safety Alert

• Excretion of Uric acid from the blood through the kidneys can cause nephropathy if adequate fluids are not consumed.
• Ingesting at least 3 L/day of fluid will dilute the urine so the kidneys are not damaged.

Contraindications and Precautions

• Allopurinol is contraindicated in clients who are hypersensitive to it.
• Use allopurinol with caution in clients who have bone marrow depression, liver or renal dysfunction, peptic ulcer disease, or lower gastrointestinal tract disease.

Interactions

• Allopurinol increases the anticoagulant effect of warfarin, so use lower dosages and closely monitor clotting time.
• Concurrent administration of allopurinol with mercaptopurine, theophylline, and azathioprine increases their potential for toxicity.
• The use of ampicillin with allopurinol increases clients’ risk for rash.