1.

Title & synonyms :

Brand name : Thyreostat II Forms : Common synonyms: Procasil Propacil Propilthiouracil PropycilPropyl-Thiorist - Propyl-Thiorit - Propyl-Thyracil Propylthiorit Propythiouracil - Prothiucil Prothiurone Prothycil Prothyran Protiural PTU Thiuragyl

Preparation or combination : Graphic drug formula :

2.Chemistry &stability :
Chemical & structure description :

IUPAC name : 6-propyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidin-4one

Physical description : Odorless white crystalline powder of starch-like

appearance. Bitter taste. Saturated solution is neutral or slightly acid to litmus Sensitive to light. May be sensitive to prolonged exposure to air. Insoluble in water. Propylthiouracil is incompatible with strong oxidizing agents, strong acids and strong bases. Forms complexes with divalent metals. Reacts with sulfhydryloxidizing agents . When reduced will produce hydrogen sulfide.
mp Fp storage temp. Water Solubility Merck Stability: Absorption Protein binding Metabolism Route of elimination Half life Clearance Toxicity Affected organisms Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours. 2 hours Not Available Oral, rat: LD50 = 1250 mg/kg. 218-220 C(lit.) 300 C Refrigerator 1.1 g/L 7869 Stable. Combustible. Incompatible with strong oxidizing agents, strong acids, strong bases. Light sensitive. Well absorbed following oral administration. 82%

Volume of distribution Not Available

Humans and other mammals

DRUG CLASS AND MECHANISM: Propylthiouracil (PTU) is used to manage hyperthyroidism which is due to an overactive thyroid gland. It is considered an anti-thyroid agent, like methimazole (Tapazole). Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4 ) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. (PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones.) GENERIC AVAILABLE: yes PRESCRIPTION: yes PREPARATIONS: Tablet: 50mg.

STORAGE: PTU should be stored at room temperature, 15-30C (59-86F). PRESCRIBED FOR: PTU is used to manage hyperthyroidism associated with Grave's disease. It is also used to decrease symptoms of hyperthyroidism in preparation for surgically removing the thyroid gland or before inactivating the thyroid gland with radioactive iodine therapy. PTU may also be used when it is not advisable to remove the thyroid gland. DOSING: The initial adult dose of PTU is 300 mg/day. The drug should be taken every eight hours. Occasionally adult doses may exceed 300 mg/day if moderate or severe hyperthyroidism is present. A common, long-term adult dose after initial treatment is 100-150 mg/day. Children's initial and continuing doses vary. DRUG INTERACTIONS: PTU may increase the effect of oral blood thinners, for example warfarin (Coumadin). Therefore, warfarin dose changes and monitoring for the effects of warfarin on blood clotting are necessary. PREGNANCY: There is evidence that PTU may cause harm to the fetus during pregnancy. If hyperthyroidism becomes more severe during pregnancy, however, PTU may be considered useful under physician supervision. NURSING MOTHERS: There is evidence that PTU may cause harm to the fetus during nursing. Use of PTU while nursing should be done under careful physician supervision. SIDE EFFECTS: PTU is generally well-tolerated with side effects occurring in 1 of every 100 patients. The most common side effects are related to the skin and include rash, itching, hives, abnormal hair loss, and skin pigmentation. Other common side effects are swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headache. Less common but serious side effects have occurred with PTU therapy. A decrease of white blood cells in the blood (agranulocytosis) may occur. Symptoms and signs of agranulocytosis include infectious lesions of the throat, the gastrointestinal tract and skin with an overall feeling of illness and fever. A decrease in blood platelets (thrombocytopenia) also may occur. Since platelets are important for the clotting of blood, thrombocytopenia may lead to problems with excessive bleeding. There also have been rare occurrences with PTU of hepatitis and death of liver cells (hepatic necrosis). Failure of the liver due to hepatic necrosis may lead to severe brain swelling, gastrointestinal bleeding, and death.
Reference: FDA Prescribing Information

Used to manage hyperthyroidism which is due to an overactive thyroid gland (Grave's disease). Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid Pharmacodynamics hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases Indication

Mechanism of action

thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole. Propylthiouracil binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.

Important warning : Propylthiouracil may cause severe liver damage in adults and
children. Some people who took propylthiouracil needed liver transplants and some people died because of the liver damage. Because of this risk, propylthiouracil should only be given to people who cannot receive other treatments such as surgery, radioactive iodine, or a different medication called methimazole (Tapazole). Propylthiouracil may also be given to women during the first months (about 12 weeks) of pregnancy because methimazole may cause birth defects if it is used during this part of a pregnancy. If you are taking propylthiouracil, call your doctor immediately if you develop any of the following symptoms: fever, loss of appetite, nausea, vomiting, tiredness, itching, dark urine, pale or light colored stools, yellowing of the skin or eyes, or pain in the upper right part of the stomach. Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with propylthiouracil and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm).

http://www.drugbank.ca/drugs/DB00550 http://www.chemicalbook.com/ProductChemicalPropertiesCB9777662 _EN.htm http://www.medicinenet.com/propylthiouracil/article.htm