Additive nephrotoxicity from roentgenographic contrast media. Its occurrence in phenazopyridine-induced acute renal failure.

A 68-year-old woman had reversible nonoliguric acute renal failure and yellow pigmentation of her skin and sclerae after ingesting phenazopyridine hydrochloride, 200 mg four times a day for six weeks. Although she began to recover renal function promptly after the drug therapy was discontinued, there was a further decline in her glomerular filtration rate after an oral cholecystogram and intravenous pyelogram. Phenazopyridine-induced acute renal failure is rare, but its early recognition is important so that additional nephrotoxicity from studies using roentgenographic contrast material may be avoided in patients with this problem.

Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents.

Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate). After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change. By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15%. The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled. After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism. In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine. The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion. the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism.

Clinical review 129: Oral cholecystographic agents and the thyroid.

Oral cholecystographic agents (OCAs) are known to affect thyroid hormone metabolism by acting as potent inhibitors of type I and type II deiodinases, blocking the conversion of T(4) to T(3) and rT(3) to T(2). In addition, iodine released from the drug blocks thyroid gland secretion of thyroid hormone. These properties make OCAs a potentially useful drug therapy in patients with hyperthyroidism and other thyrotoxic disorders. Short-term treatment with OCAs rapidly reduces serum T(3) levels, with a lesser effect on T(4) levels. OCAs are not useful for long-term treatment, which is usually followed by exacerbation of hyperthyroidism with continued use. The lack of significant side effects makes these drugs an excellent short-term option in situations where a rapid clinical improvement is critical.

Nephrotoxicity of sodium iopanoate in hydrated and dehydrated dogs.

The nephrotoxic effect of sodium iopanoate, infused intravenously in dosages of 1.5, 3 and 6 g over a 2-hour period in eight dogs (22--27 kg) in both the hydrated and dehydrated stages, were investigated. On biochemical, hemodynamic and morphological studies, the nephrotoxic effect was found to be clearly dose-dependent and greater in the dehydrated stage. Previously suggested mechanisms for acute renal failure, such as a direct tubular toxicity, tubular obstruction and hypotension, could not be supported as main factors in the development of acute renal failure post-cholecystography, although they might well have a contributory effect. The primary cause of renal failure post-cholecystography cannot be determined unequivocally from this investigation. However, the observed findings would appear to be consistent with a toxic effect of iopanoate in the small vessels possibly resulting in ischemic tubular necrosis.

Iododerma occurring after orally administered iopanoic acid.

A 45-year-old man with multiple myeloma developed iododerma after oral cholecystography with iopanoic acid. The lesions appeared two days after two exposures to iopanoic acid given within one week. To our knowledge, this is the first reported case of iododerma in association with multiple myeloma and orally ingested radiocontrast dye.

Acute thrombocytopenia following oral cholecystography with iopanoic acid.

We report a case of severe thrombocytopenia following oral cholecystography with iopanoic acid, a widely used contrast medium. A bone marrow aspirate showed increased numbers of megakaryocytes, suggesting a thrombocytopenia due to enhanced peripheral destruction of platelets; this examination was not reported in the previously described two cases. Although hematological reactions due to iopanoic acid are very rare, it would be wise to question patients regarding any preceding drug-induced purpura before proceeding with oral cholecystography.

Comparison of oral cholecystopaques: iopronic acid vs. iopanoic acid.

A new oral cholecystopaque, iopronic acid, was compared to iopanoic acid. This was a double blind, randomized study of 260 subjects. A 4.5-G dose of iopronic acid produced a similar degree of gallbladder opacification as 3.0 g of iopanoic acid. Adverse reactions to the contrast media were generally mild, but were significantly less with iopronic acid. The present study is criticized because it was not designed to help the radiologist determine the better contrast medium under optimal clinical conditions.

Fractionated dose cholecystography: a comparison between iopanoic acid and sodium ipodate.

Two randomised groups of 100 subjects each, undergoing oral cholecystography, were given either a 6 g fractionated dose of iopanoic acid (Telepaque) or sodium ipodate (Biloptin) to determine the relative merits of this dose schedule. Exclusions to the study were pregnancy and iodine sensitivity. Calculi or abnormal gallbladder opacification were present in 45% of subjects. Both agents were equally effective in demonstrating abnormalities, although bile duct visualisation was better using iopanoic acid (P less than 0.05). Of 46 subjects with abnormal cholecystograms subsequently undergoing surgery, all had the diagnosis confirmed. Side effects occurred in 63% of all subjects, being twice as common in those taking iopanoic acid (P less than 0.01). Sodium ipodate in a large fractionated dose is favoured because of the lower occurrence of side effects without loss of diagnostic accuracy.

Thrombocytopenic purpura following iopanoic acid ingestion.

A 48-year-old woman had severe symptomatic thrombocytopenia three times in 13 months. Each episode followed ingestion of iopanoic acid. The interval between drug ingestion and onset of symptoms was 40, 12, and 8 hours. Resolution to normal platelet counts occurred in 6, 5, and 8 days. The third thrombocytopenic crisis occurred while the patient was receiving maintenance steroid therapy, given because the initial diagnosis was idiopathic thrombocytopenic purpura. Incubation of platelet-rich plasma with the patient's serum caused platelet lysis if either the patient or the donor serum obtained after ingestion of iopanoic acid was present in the mixture.

Clinical comparison of two contrast agents for oral cholecystography: radiologic efficacy and drug safety of iopanoic acid and iopronic acid.

Oral doses of either iopronic acid (4.5 g Oravue, Squibb) or iopanoic acid (3 g Telepaque, Winthrop) were given to 98 patients requiring cholecystography. Radiographs were taken 13 to 16 hours after treatment showed good to excellent gallbladder opacification in 44 percent of patients after the first dose of iopronic acid and in an additional 29 percent after a second dose. Similar opacification occurred in 42 percent of patients after the first dose of iopanoic acid and in 34 percent after a second dose. Drug-related abnormalities in blood and urine tests occurred about equally in both groups and one patient in each group exhibited a clinically adverse reaction (diarrhea). Thus, the performance (radiographic efficacy and drug safety) of the new contrast agent, iopronic acid, was similar to a widely used drug, iopanoic acid.