6-propylthiouracil

Although several metaboUtes of propylthiouracil have been found (36,44), it is mainly excreted in urine as the glucuronide. Its relatively short plasma half-life requires that it be adniinistered four times daily. 

Propylthiouracil. This compound is a white, powdery, crystalline substance of starch-like appearance with a bitter taste. It is slightly soluble in water, chloroform, and ethyl ether, sparingly soluble in ethanol, and soluble in aqueous alkaline solutions (53). An extensive compilation of its chemical, spectral, and chromatographic properties is available (43). It is assayed titrimetrically with NaOH (53). 

Hyperthyroidism may be treated in several ways. One of these is interference with the synthesis of the thyroid hormones, possibly by removal of iodine. Thiourea and cyclic thioureas have this effect and of such cyclic compounds, thiouracil (1030 R = H), its 6-alkyl derivatives (1030 R = Me or Pr) and thiobarbital (1031) are effective thyroid drugs. Today only propylthiouracil (1030 R = Pr) is widely used, probably because it has fewer side effects than the others (71MI21302). The thiouracils are made by the Principal Synthesis from a /3-oxo ester (1032 R = H, Me, Pr, etc.) and thiourea (45JA2197) their fine structures are experimentally based (64AF1004). 

Propylthiouracil (PTU), but not methyl-mercaptoi-midazole (MMI), has an additional peripheral effect. It inhibits the monodeiodination of thyroxine to triiodothyronine by blocking the enzyme 5 mono-deiodinase [1]. In humans the potency of MMI is at least 10 times higher than that of PTU, whereas in rats PTU is more potent than MMI. The higher potency of MMI in humans is probably due to differences in uptake into the thyroid gland and subsequent metabolism, because in vitro inhibition of thyroid peroxidase by MMI is not significantly more potent than by PTU [1, 6]. Whether antithyroid drags have additional immunosuppressive actions is a matter of discussion [1, 2]. 

Hyperthyroidism (thyrotoxicosis), defined as excessive thyroid activity, causes a state of thyroid hormone excess (thyrotoxicosis) characterized by an increased metabolic rate, increase in body temperature, sweating, tachycardia, tremor, nervousness, increased appetite and loss of weight. Common causes of hyperthyroidism are toxic multinodular goiter, toxic adenoma or diffuse toxic goitre ( Graves disease). Antithyroid diugs (methimazol, carbimazole, propylthiouracil) block thyroid hormone production and are hence suitable for the treatment of hyperthyroidism. 

There is an additive bone marrow depression when methimazole or propylthiouracil is administered with otiier bone marrow depressants, such as the antineo-plastic drugs, or witii radiation therapy. When methimazole is administered with digitalis, there is an increased effectiveness of the digitalis and increased risk of toxicity. There is an additive effect of propylthiouracil when the drug is administered with lithium, potassium iodide, or sodium iodide When iodine products are administered with litiiium products, synergistic hypotiiyroid activity is likely to occur. 

Agranulocytosis is potentially the most serious adverse reaction to methimazole and propylthiouracil. The nurse notifies the primary health care provider if fever, sore throat, rash, headache, hay fever, yellow discoloration of the skin, or vomiting occurs. 

If Hie patient experiences a rash while taking methimazole or propylthiouracil, tlie nurse carefully documents Hie affected areas, noting size, texture, and extent of tlie rash, and reports tlie occurrence of Hie rash to tlie primary health care provider. Soothing creams or lubricants may be applied, and soap is used sparingly, if at all, until Hie rash subsides. 

Propylthiouracil (preferred thionamide, as it blocks peripheral conversion of T4 — T3)... 

Diclofenac, fenofibrate, lovastatin, methyldopa, minocycline, nitrofurantoin, phenytoin, and propylthiouracil... 

Acetaminophen, bosentan, diclofenac, isoniazid, lovastatin, methyldopa, niacin, nefazodone, phenytoin, propylthiouracil, rifampin, trazodone, valproic acid, and venlafaxine... 

Allopurinol, aspirin, carbamazepine, chlorpropamide, clomipramine, clozapine, colchicine, desipramine, gold salts, imipramine, levodopa, penicillamine, phenothiazines, phenytoin, propylthiouracil, and sulfonylureas... 

Acetazolamide, allopurinol, aspirin, captopril, carbamazepine, chloramphenicol, chlorpromazine, dapsone, felbamate, gold salts, metronidazole, methimazole, penicillamine, pentoxifylline, phenothiazines, phenytoin, propylthiouracil, quinidine, sulfonamide antimicrobials, sulfonylureas, and ticlopidine... 

One month later, GD is back for a follow-up visit. She notes that her thyrotoxic symptoms are gone, and overall, she feels great. She is receiving propylthiouracil 100 mg three times daily. Her most recentTSH was 0.9 milliunit/L (normal 0.5-2.5 milliunits/L), and her free T4 was 1.6 ng/dL (20.6 pmol/L normal 0.7-1.9 ng/dL, or 9.0-24.5 pmol/L). However, over the past few days she has developed a sore throat and feels achy. She wonders if she has the flu. Her vital signs show a pulse of 92 beats/minute and a temperature of 38.3°C (101 °F). A complete blood count reveals a total white blood cell count of 1 00/mm3 or 0.1 x 1 09/L (normal 4000-10,000/mm3 or 4-10 x 1 09/L) with 15 neutrophils (absolute neutrophil count 150). 

Some neonates born to mothers with Graves disease will be hyperthyroid at delivery. Antithyroid drug therapy (propylthiouracil 5-10 mg/kg per day or methimazole 0.5-1 mg/kg per day) may be required for up to 12 weeks. One drop per day of SSKI may be used in the first few days to rapidly reduce thyroid hormone synthesis and release. 

Treat pregnant hyperthyroid women with propylthiouracil. 

One excellent study [151] employed intravenous and oral dosing at each of several times postsurgery (1-2 weeks, 6 and 12 months). This design permits valid conclusions about the absorption process. There was a significant reduction after surgery in ampicillin absorption but no change in propylthiouracil absorption. 

JP Kampmann, H Klein, B Lumholtz, JEM Hansen. Ampicillin and propylthiouracil pharmacokinetics in intestinal bypass patients followed up to a year after operation. Clin Pharmacokinet 9 168-176, 1984. 

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