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Antithyroid DrugAka: Thioamide, Propylthiouracil, PTU, Methimazole, Tapazole

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  1. See Also
    1. Hyperthyroidism
    2. Hyperthyroidism Management
  2. Indications
    1. Hyperthyroidism in children and adolescents
    2. Pregnancy (PTU)
    3. Severe Grave's Disease (e.g. Thyroid Storm)
    4. Subclinical Hyperthyroidism
  3. Dose: Grave's Disease
    1. Target dose to Free T4 high end of normal range
    2. Propylthiouracil (PTU)
      1. Advantages over Methimazole
        1. No contraindication in Liver Disease
        2. Preferred in pregnancy (both are Category D)
      2. Dosing: Hyperthyroidism
        1. Start: 100 mg po tid
        2. Maximum: 150 mg every 6-8 hours
        3. Titrate PTU dose down after 4-6 weeks
          1. Goal: maintain normal Thyroid function
          2. Dose: reduce to 50-100 mg per day
      3. Dosing: Other
        1. Thyroid Storm: 1 gram load, then 300 mg PO q6 hours
        2. Subclinical Hyperthyroidism: 50-100 mg PO qd
    3. Methimazole (Tapazole)
      1. Advantages over Propylthiouracil (PTU)
        1. Once daily dosing
        2. Decreases T4 and T3 levels more rapidly
        3. Lower risk of Agranulocytosis at moderate doses
      2. Dosing: Hyperthyroidism
        1. Start: 10-30 mg PO qd
        2. Titrate Methimazole dose down after 4-6 weeks
          1. Goal: maintain normal Thyroid function
          2. Dose: reduce to 5-10 mg per day
      3. Dosing: Other
        1. Subclinical Hyperthyroidism: 5 mg PO qd
  4. Adverse effects (3 per 1000 patients)
    1. Drug-Induced Agranulocytosis (more common with PTU)
      1. Risk: over age 40 years
      2. Presentation: Infection (e.g. Pharyngitis)
      3. Course
        1. Resolves within 2-3 weeks after drug stopped
        2. Severe, refractory course may occur
      4. Contraindication to further antithyroid drugs
    2. Jaundice
      1. Cholestatic Jaundice
      2. Occurs more commonly with Methimazole
    3. Hepatitis
      1. Higher risk with Methimazole
      2. Propylthiouracil (PTU) may cause slight ALT increase
      3. No change in dose or medication required
    4. Vasculitis
    5. Lupus-like syndrome
    6. Aplastic Anemia
    7. Rash or Pruritus
      1. Switch from PTU to methimazole if severe
    8. Arthralgia or Polyarthritis
    9. Fever
    10. Congenital abnormalities possible with Methimazole
  5. Monitoring
    1. Repeat examination every 3 months
    2. Pregnancy Test before starting therapy
    3. Lab Testing monthly for 6 to 12 months
      1. Complete Blood Count (CBC)
      2. Liver Function Tests
      3. Thyroid Stimulating Hormone (TSH)
      4. Free T4
      5. Free T3
    4. Indications to discontinue medication
      1. TSH normalized for 6-12 months
    5. Indications to consider Thyroid ablation
      1. Inadequate suppression at 12 months from initiation
  6. Efficacy: Predictors of Relapse (occurs in 50% of cases)
    1. Tobacco abuse
    2. Large Goiter
    3. Thyroid Stmulating Antibody high at end of treatment

Methimazole (C0025644)

Definition (MSH)A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121) , Hormone (T125)
English1 Methyl 2 mercaptoimidazole, Mercasolyl, Mercazolyl, Merkazolil, Methimazole, METHIMAZOLE PREPARATION, Methylmercaptoimidazole, Methymazol, Thiamazole, Thiamazole preparation, Thimazol, Tiamazol
Spanishmetimazol, preparado de metimazol, preparado de tiamazol
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Propylthiouracil (C0033511)

Definition (MSH)A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)
Definition (PDQ)A thiourea derivative with antithyroid property. Propylthiouracil (PTU) interferes with the oxidation of iodine possibly by interaction with peroxidase or a peroxidase-mediated complex reaction, thereby inhibiting synthesis of thyroid hormones tri-iodothyronine (T3) and thyroxine (T4). In addition, this agent inhibits the Type I 5'-deiodinase (D1), an enzyme involved in the peripheral conversion of thyroxine to tri-iodothyronine. This results in decreased plasma triodothyronine concentrations and decreased entrance of thyroxine into cells thereby reducing thyroid hormone activity. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39288&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39288&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C781" NCI Thesaurus)
Definition (NCI)A thiourea derivative with antithyroid property. Propylthiouracil (PTU) interferes with the oxidation of iodine possibly by interaction with peroxidase or a peroxidase-mediated complex reaction, thereby inhibiting synthesis of thyroid hormones tri-iodothyronine (T3) and thyroxine (T4). In addition, this agent inhibits the Type I 5'-deiodinase (D1), an enzyme involved in the peripheral conversion of thyroxine to tri-iodothyronine. This results in decreased plasma triodothyronine concentrations and decreased entrance of thyroxine into cells thereby reducing thyroid hormone activity.
ConceptsNucleic Acid, Nucleoside, or Nucleotide (T114) , Pharmacologic Substance (T121)
English6 Propyl 2 Thiouracil, Propylthiouracil, PROPYLTHIOURACIL PREPARATION, Propylthiouracil product, PTU preparation
Spanishpreparado de propiltiouracilo, preparado de PTU, propiltiouracilo
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Thioamides (C0039875)

Definition (MSH)Organic compounds containing the radical -CSNH2.
Definition (CSP)compounds of the type R-(C=S)-N=.
ConceptsOrganic Chemical (T109)
Englishthioamide, Thioamides
Spanishtioamida
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Antithyroid Agents (C0040125)

Definition (CSP)any agent or substance which suppresses, prevents or opposes the biosynthesis of thyroid hormones.
Definition (MSH)Agents that are used to treat hyperthyroidism by reducing the excessive production of thyroid hormones.
ConceptsPharmacologic Substance (T121) , Hormone (T125)
Englishantithyroid agent, Antithyroid Agents, Antithyroid Drugs, THYROID ANTAG, Thyroid Antagonists, thyroid inhibitor, Thyroid inhibitor preparation
Spanishagente antitiroideo, preparado antitiroideo, preparado inhibidor tiroideo
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Tapazole (C0728778)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishEli Lilly Brand of Methimazole, Jones Brand of Methimazole, Tapazole
CreditsDerived from the NIH UMLS (Unified Medical Language System)



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