Probenecid Allopurinol

Gout is a metabolic disease in which there is a overproduction of purines. It is characterized by intermittent attacks of acute arthritis produced by the deposition of sodium urate crystals in the synovial tissue of joints. Drugs used for treating gout are allopurinol, probenecid, colchicine, and NSAIDs. 

The options available are allopurinol, probenecid (named patient only) and sulfinpyrazone. Allopurinol is the drug usually chosen as a first line agent for the prevention of gout. Colchicine may be given at a dose of 500 micrograms twice or three times daily when allopurinol or uricosuric drugs are initially commenced in order to prevent an attack of gout. NSAIDs may also be used but this would not be an appropriate option for Mr KT. 

Allopurinol Probenecid and sulfinpyrazone Inhibits xanthine oxidase and reduces purine metabolism into uric acid Reduce reabsorption of uric acid in the kidney... 

Patients with recurrent attacks, evidence of tophi or joint destruction, or uric acid nephrolithiasis are candidates for maintenance therapy with allopurinol or probenecid to lower serum uric add levels. 

Gout is one of the most ancient diseases its clinical characteristics have been known for at least 2000 years. It is now very effectively treated with drugs that decrease production of uric acid by inhibition of the enzyme xanthine oxidase in purine degradation (Figure 10.9) (allopurinol), and a drug that increases the excretion of uric acid (probenecid)... 

Drugs that may affect ACEIs may include antacids, capsaicin, indomethacin, phenothiazines, probenecid, and rifampin. Drugs that may be affected by ACEIs include allopurinol, digoxin, lithium, potassium preparations/potassium-sparing diuretics, and tetracycline. 

Drugs that may be affected by probenecid include acyclovir allopurinol barbiturates benzodiazepines clofibrate dapsone dyphylline methotrexate NSAIDs pantothenic acid penicillamine rifampin sulfonamides sulfonylureas zidovudine salicylates. 

Drugs that may affect penicillins include allopurinol, aminoglycosides (parenteral), aspirin, beta blockers, chloramphenicol, erythromycin, ethacrynic acid, furosemide, indomethacin, phenylbutazone, probenecid, sulfonamides, tetracycline, and thiazide diuretics. Drugs that may be affected by penicillins include aminoglycosides (parenteral), anticoagulants, beta blockers, chloramphenicol, cyclosporine, oral contraceptives, erythromycin, heparin, and vecuronium. 

T effects W probenecid, disulfiram, T risk of rash W/ allopurinol, effects OF OCP, effects W/ tetracyclines, chloramphenicol EMS See Amoxicillin Amphotericin B (Amphecin) [Antifungal/Pelyene Macrolide]... 

Mercaptopurine [6-MP] (Purinethol) [Antineoplastic/ Antimeta lite] Uses Acute leukemias, 2nd-line Rx of CML NHL, maint ALL in children, immunosuppressant w/ autoimmune Dzs (Crohn Dz) Action Antimetabolite, mimics hypoxanthine Dose Adults. 80-100 mg/mVd or 2.5-5 mg/kg/d maint 1.5-2.5 mg/kg/d Peds. Per protocol X w/ renal/hepatic insuff on empty stomach Caution [D, ] Contra Severe hepatic Dz, BM suppression, PRG Disp Tabs SE Mild hematotox, mucositis, stomatitis, D rash, fever, eosinophilia, jaundice. Hep Interactions T Effects W/ allopurinol T risk of BM suppression W/ trimethoprim-sulfamethoxazole X effects OF warfarin EMS May falsely T glucose OD May cause NA and liver necrosis symptomatic and supportive Meropenem (Merrem) [Antibiotic/Carbapenem] Uses lntra-abd Infxns, bacterial meningitis Action Carbapenem X cell wall synth, a [3-lactam Dose Adults. 1 to 2 g IV q8h Peds. >3 mo, <50 kg 10-40 mg/kg IV q 8h in renal insuff Caution [B, ] Contra [3-Lactam sensitivity Disp Inj 500 mg, 1 g SE Less Sz potential than imipenem D, thrombocytopenia Interactions T Effects W/ probenecid EMS Monitor for signs of electrolyte disturbances and... 

Allopurinol, chloramphenicol, isoniazid Antipyrine, dicumarol, probenecid, tolbutamide... 

When chemotherapeutic mercaptopurines (eg, azathioprine) are given concomitantly with allopurinol, their dosage must be reduced by about 75%. Allopurinol may also increase the effect of cyclophosphamide. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants... 

In a pathological condition that causes pain, drugs may be used either to care for the acute attack of pain or as prophylaxis to prevent the occurrence of pain. For example, colchicine is used during an acute attack of gout, and after the pain has subsided initially, the patient is switched to uricosuric agents such as probenecid or an inhibitor of uric acid synthesis such as allopurinol. 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Were JB, Shapiro TA. Effects of probenecid on the pharmacokinetics of allopurinol riboside. Antimicrob Agents Chemother 1993 37 1193-1196. 

Aspirin, salicylates, and thiazide diuretics should not be used with allopurinol. The dose of mercaptopurine should be reduced one-third or one-fourth when used with allopurinol. Acute poisoning of colchicine should be treated with gastric lavage and activated charcoal administration. Supportive maintenance measures for blood pressure and respiration should be provided. Probenecid is used by athletes to inhibit the urinary excretion of banned anabolic steroids.85... 

Fasted Cebus monkeys (Cebus albifrons) of either sex weighing 3.0 to 5.0 kg are used. On the morning of the experiment, the animals receive 20 ml/kg drinking water by gavage, followed by oral administration of the test compound. Allopurinol and probenecid are used as control compounds. Control animals receive water only. The animals are placed in individual metabolism cages and the spontaneously voided urine is collected after 2, 6, and 24 h. After 2 and 6 h, an additional 4 ml/kg water is given by gavage. From a cubital vein blood is withdrawn prior to the experiment and 2, 6 and 24 h after application. 

Prophylaxis Prophylactic treatment of patients with uric acid-lowering agents such as allopurinol or probenecid should not be started until the acute attack resolves. This is because these agents cause mobilization of urate crystals and may prolong the acute attack. Patients may need long-... 

Agents used to treat acute gout attacks as well as to prevent recurrent attacks should be used with caution in patients with hypertension and renal impairment. Doses may need to be adjusted in patients with decreased renal function. Probenecid is usually recommended for patients who are under 60 years of age, who have normal renal function, are diagnosed as an underexcreter, and have no history of kidney stones. Probenecid causes a marked increase of uric acid in the urine, and decreased renal elimination places the patient at risk for stone formation. Allopurinol is a good choice for patients with uric acid stones or renal insufficiency, as well as for those who are known to be overproducers of uric acid. 

Prototype agents Indomethacin Ibuprofen Naproxen Colchicine Prednisone Probenecid Allopurinol... 

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