Propylthiouracil

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Propylthiouracil
Clinical data
Other names6-n-propylthiouracil (PROP)
AHFS/Drugs.comMonograph
MedlinePlusa682465
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • US: WARNING[2]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability80%-95%
Metabolism?
Elimination half-life2 hours
Excretion?
Identifiers
  • 6-propyl-2-sulfanylpyrimidin-4-one
JSmol)
Melting point219 to 221 °C (426 to 430 °F)
  • S=C1N/C(=C\C(=O)N1)CCC
  • InChI=1S/C7H10N2OS/c1-2-3-5-4-6(10)9-7(11)8-5/h4H,2-3H2,1H3,(H2,8,9,10,11) checkY
  • Key:KNAHARQHSZJURB-UHFFFAOYSA-N checkY
  (verify)

Propylthiouracil (PTU) is a medication used to treat

radioactive iodine is not possible.[3] It is taken by mouth.[3]

Common side effects include itchiness, hair loss, parotid swelling, vomiting, muscle pains, numbness, and headache.

thyroxine (T4) to triiodothyronine (T3).[3]

Propylthiouracil came into medical use in the 1940s.[5] It is on the World Health Organization's List of Essential Medicines.[6]

Side effects

Propylthiouracil is generally well tolerated, with side effects occurring in one of every 100 patients.[citation needed] The most common side effects are related to the skin and include rash, itching, hives, abnormal hair loss, and skin pigmentation.[citation needed] Other common side effects are swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headache, allergic reactions, and hair whitening.[citation needed]

Its notable side effects include a risk of

FDA published an alert "notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil."[7] As a result, propylthiouracil is no longer recommended in non-pregnant adults and in children as the front line antithyroid medication.[8]

One possible side effect is agranulocytosis,[9] a decrease of white blood cells in the blood. 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. Side effects are suspected and the drug is sometimes discontinued if the patient complains of recurrent episodes of sore throat.

Another life-threatening side effect is sudden, severe,

fulminant liver failure resulting in death or the need for a liver transplantation, which occurs in up to 1 in 10,000 people taking propylthiouracil. Unlike agranulocytosis which most commonly occurs in the first three months of therapy, this side effect may occur at any time during treatment.[8]

Pregnancy

Propylthiouracil is classified as

methimazole is preferred to avoid the risk of liver complications from PTU in the mother.[8]

The primary effect on the fetus from transplacental passage of PTU is the production of a mild hypothyroidism when the drug is used close to term. This usually resolves within a few days without treatment. The hypothyroid state may be observed as a goiter in the newborn, and is the result of increased levels of fetal pituitary thyrotropin.[11] The incidence of fetal goiter after PTU treatment in reported cases is approximately 12%.

Mechanism of action

Thyroid

Thyroid hormone synthesis
, with the oxidation step labeled at center-left.

PTU inhibits the enzyme

thyroxine (T4).[12]

PTU does not inhibit the action of the

sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors, such as perchlorate and thiocyanate
.

T3/T4 target tissues

PTU also acts by inhibiting the enzyme 5'-deiodinase (

methimazole
, which shares propylthiouracil's central mechanism, but not its peripheral one.)

It is important to recognize that these enzymes only work on the conjugated tyrosine molecules of T3 and T4: a completely different enzyme family is responsible for the deiodinase activity of iodized single tyrosine molecules within the thyroid follicular cells. For information on that enzyme family, see Iodotyrosine deiodinase.

Pharmacokinetics

The administration is oral, with peak serum concentrations occurring in one hour, and actively concentrated to the thyroid gland. Depending on several patient variables, however, euthyroid status may not be achieved until 2–4 months after treatment initiation. Of note, the drug is approximately 70% protein-bound and significantly ionized at normal physiologic pH, while the antithyroid agent

methimazole is substantially less protein bound. However, both are equally transferred across the placenta.[13]

The plasma half-life is one hour and is not altered appreciably by the thyroid status of the patient. Due to the concentration in the thyroid, however, dosing intervals may last 8 hours or longer. Less than 10% of the drug is excreted unchanged, with the remaining fraction undergoing extensive hepatic metabolism via glucuronidation.

Chemical synthesis

Propylthiouracil can be prepared from ethyl 3-oxohexanoate and thiourea.[14]

Role in taste

Propylthiouracil, together with phenylthiocarbamide (PTC), are known to have bitter taste.[15] However, it seems the propensity for tasting these compounds is genetically based and the bitter taste is likely to be engendered by the thiocyanate moiety, also present in PTC.[15]

History

It was approved by the United States Food and Drug Administration in 1947.

References

  1. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Retrieved 13 May 2022.
  2. FDA
    . Retrieved 22 Oct 2023.
  3. ^ a b c d e f g h i "Propylthiouracil". The American Society of Health-System Pharmacists. Archived from the original on 27 December 2016. Retrieved 8 December 2016.
  4. ISBN 9780857111562
    .
  5. ISBN 978-0323221535. Archived
    from the original on 2016-12-26.
  6. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. FDA. Archived
    from the original on 2009-06-06. Retrieved 2009-05-03.
  8. ^
    PMID 19583480
    .
  9. PMID 16491833. Archived from the original
    on 2008-12-22.
  10. ^ "propylthiouracil". Online.epocrates.com. Archived from the original on 2013-12-03. Retrieved 2013-11-29.
  11. S2CID 28728514
    .
  12. ^ Boron WF, Boulpaep EL (2005). Medical Physiology (Updated ed.). Philadelphia, PA: Elsevier Saunders.
  13. PMID 17948378
    .
  14. PMID 21005687
    .
  15. ^
    PMID 15723792
    .

External links

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