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Results for “Propylthiouracil”

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At least 19 recordsLinked to original sources

PubMed1975

Stimulation by propylthiouracil of the hexose monophosphate shunt in human polymorphonuclear leucocytes during phagocytosis.

The effect of propylthiouracil on glucose metabolism in human polymorphonuclear leucocytes was studied. At a therapeutically achievable concentration (0.1 mM), propylthiouracil stimulated hexose monophosphate shunt activity in normal leucocytes during phagocytosis but not in resting cells. However, in the presence of hydrogen peroxide it stimulated hexose monophosphate shunt activity in resting cells, and in the soluble fraction when reduced glutathione and reduced nictotinamide adenine dinucleotide phosphate (NADPH) were also present. Propylthiouracil had nor effect on glucose-1-C oxidation in either phagocytosing or resting leucocytes obtained from two male patients with chronic granulomatous disease. Stimulation of the hexose monophosphate shunt activity in normal leucocytes during phagocytosis also was demonstrated with methimazole, thiouracil and thiourea, but not with adenine, uracil or urea. There was an apparent minimal common structure requirement in thriourea. Propylthiouracil had no effect on phagocytosis, formate oxidation, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase or catalase activities. Thus, the stimulation of the hexose monophosphate shunt activity by propylthiouracil is dependent on hydrogen peroxide and is best explained by its stimulation or participation in the glutathione cycle.

Blood Glucose↗

PubMed1990

Conformational changes of peroxidase and albumin in solutions of propylthiouracil.

Conformational changes of peroxidase and albumin in buffered solutions of propylthiouracil, an antithyroid drug, were evaluated by dialtometry and viscometry, showing that the structural alteration of peroxidase is related to the decoupling of the reactions which it catalyses. Thus, propylthiouracil probably inactivates the peroxidase by altering its structure. Equilibrium dialysis showed that albumin is the principle propylthiouracil-transporting protein in human serum. Propylthiouracil induces a conformational change in albumin when 1 mole of drug per mole of protein is bound, a structural alteration that can change the binding capability of other ligands.

Chemical Phenomena↗

PubMed1979

The effect of propylthiouracil on thyroid-stimulating hormone-induced alterations in iodothyronine secretion from perfused dog thyroids.

The aim of this study was to see whether the inhibitory effect of propylthiouracil on thyroidal secretion of 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) could be reproduced in intensively stimulated thyroids, and to elucidate whether an increase in the fractional deiodination of thyroxine (T4) to T3 and rT3 during iodothyronine secretion might be responsible for the transient fall in the T4/T3 and T4/rT3 ratios in thyroid secretion seen in the early phase after stimulation of thyroid secretion. For this purpose T4, T3 and rT3 were measured in effluent from isolated dog thyroid lobes perfused in a non-recirculation system using a synthetic hormone free medium. 1 mmol/1 propylthiouracil induced a significant reduction in thyroid-stimulating hormone (TSH) stimulated T3 and rT3 release while the release of T4 was unaffected. This supports our previous conclusion that T4 is partially monodeiodinated to T3 and rT3 during thyroid secretion. Infusion of 1 mmol/l propylthiouracil for 30 min or 3 mmol/l propylthiouracil for 120 min did not abolish the transient fall in effluent T4/T3 and T4/rT3 induced by TSH stimulation. Thus, this phenomenon seems not to depend on intrathyroidal iodothyronine deiodinating processes.

Animals↗

PubMed1976

Effect of propylthiouracil-induced hypothyroidism on phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin synthesis in chick liver microsomes.

Biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin was studied in liver endoplasmic reticulum obtained from newly hatched chicks which were made hypothyroid by feeding 0.2% propylthiouracil. In vitro measurements were made of the specific activities of phosphorylcholine-glyceride (cholinephosphotransferase (EC 2.7.8.2), hosphorylethanolamine-glyceride (ethanolamine-phosphotransferase (EC 2.7.8.1)), and phosphorylcholine-ceramide (ceramide cholinephosphotransferase (EC 2.7.8.3)) transferases in control and hypothyroid chick liver for a period of 40 days. The specific activity of all three transferases began to decline after the chicks were on the propylthiouracil-containing diet for 5 days and steadily declined, reaching levels 10-15% of the controls after 15 days. These low levels were maintained for as long as the chicks were on this diet. Administration of L-thyroxine (15 mug/100 g of body weight) to the hypothyroid chicks caused a marked increase in the specific activities of all three transferases, reaching levels similar to those seen in the control chicks in 36-48 h. The specific activities then declined as the chicks were maintained on the diet of propylthiouracil, reaching the former low levels after 120 h. Administration of cycloheximide alone to the hypothyroid chicks caused a rise in the specific activities of the transferases after 24 h approximately equal to that caused by thyroxine alone, while thyroxine and cycloheximide together were no different than either alone. These studies indicate that in some manner circulating thyroxine controls the activities of enzymes involved in the biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin in chick liver endoplasmic reticulum. There was no evidence that induction of hypothyroidism by propylthiouracil had any effect on the activities of these enzymes in the CNS.

Animals↗

PubMed1976

An increase of liver uptake of thyroxine, an initial step of an increased fecal loss of thyroxine in response to propylthiouracil in rats.

Propylthiouracil augmented fecal loss of thyroxine (T4), but methimazole was without effect in this respect in rats. In vitro uptake of labeled T4 by the liver was significantly enhanced by a small amount of propylthiouracil in the presence of dilute rat plasma. Methimazole was without effect under comparable conditions. In contrast, propylthiouracil and methimazole failed to affect in vitro uptake of labeled T4 by the kidney and diaphragm in the presence of dilute rat plasma. Since deiodination of T4 does not occur in the presence of dilute rat plasma, it is suggested that propylthiouracil specifically stimulates liver uptake of T4 as an initial step of an increase of biliary-fecal excretion of T4 in rats.

Animals↗

PubMed1976

Fulminant hepatitis and lymphocyte sensitization due to propylthiouracil.

Fulminant hepatic failure developed in a 24-year-old black woman who had been treated with propylthiouracil and propranolol for hyperthyroidism. Clinical and biochemical recovery followed discontinuation of drug therapy. Liver biopsy disclosed submassive hepatic necrosis. During the acute phase of the disease, lymphocyte transformation studies revealed sensitization of the patient's lymphocytes to propylthiouracil but not to propranolol. Sensitization remained demonstrable 2 months after cessation of the former drug. Lymphocytes obtained from a hyperthyroid patient treated with propylthiouracil without complications failed to show evidence of sensitization. These observations indicate that submassive hepatic necrosis may result from treatment with propylthiouracil and are consistent with the notion that sensitization mechanisms may be responsible for the hepatic injury induced by this drug.

Adult↗

PubMed1991

Treatment of supraventricular tachyarrhythmias associated with hyperthyroidism by radioiodine, amiodarone and propylthiouracil.

Beta-blockers and calcium antagonists have been advocated for thyrotoxicosis induced tachyarrhythmias. Amiodarone is generally considered as contraindicated because of its high iodine content. Since amiodarone combined with propylthiouracil induced a greater fall in serum thyroid hormone concentrations than propylthiouracil alone, we treated 2 hyperthyroid patients with supraventricular arrhythmias by radioiodine (day 0) followed after 24 h by amiodarone and propylthiouracil. Serum T3 was normalized on day 2 (patient 1) and 3 (patient 2). Effective t1/2 of intrathyroidal 131I were 6.6 and 4.3 days (versus 5.9 days for 131I given alone). In patient 1, atrial fibrillation, reverted to sinus rhythm after verapamil and digoxin, and did not recur. In patient 2, conversion of atrial fibrillation to sinus rhythm occurred on day 11; from day 0 to day 11, ventricular rate decreased and was significantly correlated to T3 (r = 0.82; p < 0.05). In conclusion, amiodarone may be beneficial in thyrotoxicosis associated tachyarrhythmias, given with propylthiouracil 24 h after radioiodine, it did not decrease thyroid irradiation and rapidly decreased serum T3.

Adult↗

PubMed1991

[Propylthiouracil in therapy of alcohol-induced liver damage?].

Propylthiouracil (Propycil Thyreostat) is presently being used in hyperthyroidism, thyroidectomy, and other diseases affecting thyroid gland metabolism. Canadian clinicians have published interesting reports showing that propylthiouracil can be used to successfully treat alcohol-induced liver damage. In two clinical trials (approximately 340 patients) it was shown that long-term treatment with propylthiouracil was associated with a significantly more favorable prognosis in cirrhosis of the liver and with a reduction in mortality. Preclinical studies suggest that alcohol abuse leads to a hypermetabolic status of the liver, which is similar to hyperthyroidism. The results of these studies suggest a rationale for the use of propylthiouracil in alcohol-induced liver cirrhosis.

Energy Metabolism↗

PubMed1979

Propylthiouracil and hepatitis: a case report.

A 10-year-old girl initially presented with clinical features and thyroid function tests consistent with hyperthyroidism. She was treated with propylthiouracil, 100 mg, three times a day. She developed jaundice and hepatitis following treatment with propylthiouracil for 40 days. Clinical features of hepatitis improved after the discontinuation of propylthiouracil and she became euthyroid. At this time, an immunofluorescent technique revealed antibodies consistent with autoimmune thyroiditis. From this report, it appears that hepatitis is one of the infrequent complications of treatment with propylthiouracil and transient hyperthyroidism may be associated with autoimmune thyroiditis.

Chemical and Drug Induced Liver Injury↗

PubMed1992

Intellectual capacity of subjects exposed to methimazole or propylthiouracil in utero.

Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.

Adolescent↗

PubMed1991

Evaluation of the antioxidant properties of thyroid hormones and propylthiouracil in the brain-homogenate autoxidation system and in the free radical-mediated oxidation of erythrocyte membranes.

The antioxidant capacity of thyroid hormones and the antithyroid drug propylthiouracil was studied in three model systems, namely, autoxidation of rat brain homogenates and oxidation of rat erythrocyte plasma membranes (EPM) induced by either 2,2'-azobis-(2-amidinopropane) (AAP) thermolysis or by gamma irradiation. Thyroid hormones significantly inhibited the development of lipid peroxidation in these systems at micromolar concentrations, as assessed either by visible light emission, thiobarbituric acid reactive substances accumulation or oxygen uptake. This behaviour was not observed when L-3,3',5-triiodothyronine (T3) and L-thyroxine (T4) were assayed at nanomolar concentrations. In EPM exposed to AAP or gamma irradiation, propylthiouracil inhibited the induced lipid peroxidation, with Q1/2 values of 112-150 microM. It is concluded that the antioxidant capacity of thyroid hormones found in vitro may not be of relevance in physiological conditions, which exhibit variations of T3 and T4 levels in the nanomolar range. On the other hand, the behaviour of propylthiouracil as an inhibitor of EPM lipid peroxidation is observed at concentrations close to the therapeutic levels, thus representing a possible complementary action to its antithyroid activity.

Animals↗

PubMed1992

Propylthiouracil-induced hypersensitivity vasculitis presenting as respiratory failure.

Hypersensitivity vasculitis associated with propylthiouracil therapy is a well-documented clinical entity. Although any organ system may be involved, it is most unusual for pulmonary manifestations to be the cardinal presenting features. We report a 72-year-old woman presenting with respiratory failure and hemoptysis following initiation of propylthiouracil therapy for Graves' disease. She had cutaneous stigmata of hypersensitivity vasculitis and diffuse pulmonary infiltrates. The infiltrates improved dramatically after discontinuation of the propylthiouracil therapy and initiation of intravenous corticosteroid therapy.

Aged↗

PubMed1978

Prospective randomized comparison of propylthiouracil.

Forty-nine patients with Graves' disease were randomly divided into two groups. One group received propylthiouracil, 150 mg every eight hours, and the other group received propylthiouracil, 450 mg as a single daily dose. All patients' conditions were evaluated clinically anc chemically at two-week intervals. The response to the divided dosage schedule was prompt and predictable, and by ten weeks all but one patient had achieved remission. The group that received the single daily dose regimen responded less favorably, and at ten weeks ten patients had failed to achieve remission (P less than .001). However, when these patients' regimens were switched to the every-eight-hour schedule, all but one patient became euthyroid in an additional four weeks.

Drug Evaluation↗

PubMed1975

Observations on the fine structure of propylthiouracil-induced "brown degeneration" in the zona reticularis of mouse adrenal cortex.

Propylthiouracil (6-propyl-2-thiouracil), an anti-thyroid agent, was fed to mice in a concentration equal to 0.1% of their diet for periods of 10 and 15 weeks. The cells of the inner zone of the adrenal cortex were examined with the electron microscope. In animals receiving propylthiouracil for ten weeks mitochondria were altered and the smooth endoplasmic reticulum (SER) showed a marked focal proliferation. In contrast to control animals rough endoplasmic reticulum was abundant and was frequently associated with the hyperplastic SER. After 15 weeks these alterations were no longer present but had been replaced by a spectrum of "brown degeneration." The less affected cells were characterized by increased numbers of liposomes and lysosomes and the more affected cells by liposomal and mitochondrial degeneration. These observations emphasize that "brown degeneration" is a true degenerative process and not a spontaneous proliferation of ceroid pigment. It is suggested that the changes described may be directly related to an alteration in cholesterol metabolism.

Adrenal Cortex↗

PubMed1975

Altered plasma half-lives of antipyrine, propylthiouracil, and methimazole in thyroid dysfunction.

In normal, nonmedicated volunteers and in patients with thyroid disorders the plasma half-lives of antipyrine, propylthiouracil, and methimazole were determined after single oral doses. The plasma half-liver plus or minus S.D. of antipyrine, propylthiouracil, and methimazole were 11.9 plus or minus 1.4 hr, 6.7 plus or minus 1.0 hr, and 9.3 plus or minus 1.4 hr, respectively, in normal volunteers, but were shortened to 7.7 plus or minus 1.2 hr, 4.3 plus or minus 0.7 hr, and 6.9 plus or minus 0.6 hr, respectively, in hyperthyroid patients. In hypothyroid patients the plasma half-lives of these drugs were prolonged to 26.4 plus or minus 4.0 hr, 24.7 plus or minus 34.5 hr, and 13.6 plus or minus 4.8 hr, respectively. Return to the euthyroid state restored plasma half-lives to or toward normal. Alterations in plasma drug half-lives during thyroid dysfunction appear to result mainly from accelerated hepatic microsomal drug metabolism in hyperthyroidism and retarded drug biotransformation during hypothyroidism.

Adult↗

PubMed1991

Selective liquid chromatographic assay for propylthiouracil in plasma.

A liquid chromatographic assay was developed to quantitate propylthiouracil in plasma using an internal standard, 5-propyl-2-thiouracil, of similar structure and physical properties. Caffeine, which coelutes with propylthiouracil, was removed by extraction from serum treated with base. No other compounds were found to interfere in the assay. The drug was extracted from plasma with chloroform with a recovery of 59.4% and the intra- and inter-assay coefficients of variation were 5.7 and 3.3%, respectively. The assay was linear to 3 micrograms/ml with a lower detection limit of 40 ng/ml for a sample volume of 1 ml.

Caffeine↗

PubMed1990

High-performance liquid chromatographic determination of propylthiouracil in plasma.

A high-performance liquid chromatographic method for the determination of the antithyroid drug propylthiouracil in dog plasma has been developed. Propylthiouracil and the internal standard, methylthiouracil, are extracted from plasma with methylene chloride at pH 6 and the organic layer is evaporated to dryness. The residue is chromatographed on a Chromspher C18 reversed-phase column using Pic B-7 (0.005 M 1-heptanesulphonic acid in water)-1% acetic acid-methanol (40:45:15, v/v/v) as the mobile phase. Quantification is achieved by monitoring the UV absorbance at 300 nm. The response is linear (0.1-15 micrograms/ml) and using 100 microliters of plasma the detection limit is 50 ng/ml. The within-run coefficient of variation is less than or equal to 5% and the accuracy is within 10% of the theoretical value at concentrations between 0.1 and 15 micrograms/ml plasma.

Animals↗

PubMed1979

Kinetics of propylthiouracil in the elderly.

The pharmakokinetics of propylthiouracil was evaluated in 9 elderly patients and compared to previous results from 6 younger subjects. By giving the drug both by the intravenous and oral route of administration it was possible to estimate the rate and extent of bioavailability. The various kinetic parameters were calculated according to a two-compartment model by use of two different methods: a graphical hand drawn one and by a special developed computer program based on a least squares minimalisation. While no significant differences could be demonstrated between the two age groups concerning volumes of distribution, clearance and extent of absorption, a large difference was found with regard to the absorption rate constant ka, which was about 3 times higher in the younger than in the elderly subjects, presumably due a reduced gastric emptying time. Considering the comparison between the two methods of calculations all the kinetics parameters were similar except ka and the slow disposition rate constant betw which were underestimated by the graphical method. It is concluded that no-age dependent changes exist concerning the kinetics of propylthiouracil except for a decreased rate of absorption. Graphical methods in pharmacokinetics are useful in obtaining distribution and elimination data but seem often biased for the evaluation of absorption rate constants.

Age Factors↗