Propylthiouracil ( PTU ) is a drug used to treat hyperthyroidism. These include hyperthyroidism due to Graves' disease and toxic multinodular goitre. In thyrotoxic crises it is generally more effective than methimazole. Otherwise, it is usually only used when methimazole, surgery, and radioactive iodine is not possible. It was taken by mouth.
Common side effects include itching, hair loss, swelling, vomiting, muscle aches, numbness, and headaches. Other severe side effects include liver problems and low blood cell count. Use during pregnancy may harm the baby. Propylthiouracil is present in the family of antithyroid drugs. It works by reducing the amount of thyroid hormone produced by the thyroid gland and blocking the conversion of thyroxine (T4) into triiodothyronine (T3).
Propylthiouracil began to be used in the 1940s. It's in the List of Essential Medicines of the World Health Organization, the most effective and safe drugs needed in the health system. The cost of wholesale in developing countries is around 3.62 USD per month. In the UK a month the cost of the NHS is about 52.51 pounds. In the United States the wholesale price is 38.34 USD per month.
Video Propylthiouracil
Side effects
Propylthiouracil is generally well tolerated, with adverse events occurring in one out of every 100 patients. The most common side effects are related to the skin and include rashes, itching, itching, abnormal hair loss, and skin pigmentation. Other common side effects are swelling, nausea, vomiting, heartburn, loss of feeling, joint or muscle pain, numbness and headaches, allergic reactions, and hair whitening.
Known side effects include the risk of agranulocytosis and aplastic anemia. On June 3, 2009, the FDA issued a warning "notifying health care professionals about the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil." As a result, propylthiouracil is no longer recommended in non-pregnant adults and in children as front-line antithyroid drugs.
One possible side effect is agranulocytosis, a decrease in white blood cells in the blood. Symptoms and signs of agranulocytosis include infection lesions of the throat, gastrointestinal tract, and skin with overall pain and fever. Reduced blood platelets (thrombocytopenia) may also occur. Because platelets are important for blood clots, thrombocytopenia can cause problems with excessive bleeding. Side effects are suspected and these drugs are sometimes discontinued if the patient complains of recurring sore throat episodes.
Other life-threatening side effects are sudden, severe, fulminant liver failure resulting in death or liver transplant, which occurs in 1 to 10,000 people who use propylthiouracil. Unlike the most common agranulocytosis in the first three months of therapy, these side effects can occur at any time during treatment.
Pregnancy
Propylthiouracil is classified as Class D Drugs in pregnancy. Class D indicates there is positive evidence of fetal risk in humans. The benefits of the mother may be greater than the risk of the fetus in a life-threatening situation. PTU is preferred over methimazole (which is also class D) only in the first trimester of pregnancy and in women who may become pregnant due to increased risk of teratogenicity of methimazole during critical organogenesis. In the second and third trimesters, this risk is reduced and methimazole is preferred to avoid the risk of liver complications from the PTU in the mother.
The main effect on the fetus from the transplacental part of the PTU is the production of mild hypothyroidism when the drug is used close to the term. It usually goes away within a few days without treatment. The hypothyroid state can be observed as mumps in newborns, and is a result of elevated levels of fetal pituitary thyrotropin. The incidence of fetal mump after PTU treatment in reported cases was about 12%.
Maps Propylthiouracil
Action mechanism
Thyroid
PTU inhibits the enzyme thyroperoxidase, which usually acts in thyroid hormone synthesis by oxidizing the iodide anion (I - ) to iodine (I 0 ), facilitating the addition of iodine to the tyrosine residue in the precursor hormone thyroglobulin. This is one of the important steps in the formation of thyroxine (T4).
PTU does not inhibit the action of a sodium-dependent iodide transporter located on the basolateral membrane of the follicle cells. Inhibition of this step requires competitive inhibitors, such as perchlorate and thiocyanate.
target network T3/T4
PTU also acts by inhibiting the 5'-deiodinase enzyme (tetraiodothyronine 5 'deiodinase), which converts T 4 to a more active form T 3 . (This differs from methimazole, which shares a propylthiouracil center mechanism, but not a peripheral.)
It is important to recognize that these enzymes only work on T3 and T4 conjugated tyrosine molecules: completely different enzyme families responsible for the deiodinase activity of a single iodine tyrosine molecule in the thyroid follicle cells. For information on the enzyme's family, see Iodotyrosine deiodinase.
Pharmacokinetics
Oral administration, with peak serum concentrations occurring within an hour, and actively concentrating on the thyroid gland. Depending on some patient variables, the eutyroid status may not be reached for 2-4 months after starting treatment. Of note, the drug is about 70% protein bound and significantly ionized at normal physiological pH, whereas the anthyroid agent methimazole is substantially less attached to the protein. However, both are equally transferred to the placenta.
The half-life of plasma is one hour and is not clearly altered by the patient's thyroid status. Because of the concentration in the thyroid, however, the dose interval can last 8 hours or longer. Less than 10% of the drug is excreted unchanged, with the remaining fraction undergoing extensive liver metabolism through glucuronidation.
Chemical synthesis
Propylthiouracil can be prepared from ethyl 3-oxohexanoate and thiourea.
Role in taste
Propylthiouracil, along with phenylthiocarbamide (PTC), is known to have a bitter taste. However, it seems that the tendency to taste these compounds is genetically based and the bitter taste likely to be generated by the thiocyanate, is also present in the PTC.
History
It was approved by the Food and Drug Administration in 1947.
See also
- Phenylthiocarbamide
- Supertaster
- TAS2R38
- Methylthiouracil
References
External links
- "Clinical Clinical Pharmacology Database". Archived from the original in 2007-12-16.
Source of the article : Wikipedia
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