MECHANISM OF THIOAMIDE ANTITHYROID DRUG ASSOCIATED HYPOPROTHROMBINEMIA

@article{Lipsky1988MECHANISMOT,
  title={MECHANISM OF THIOAMIDE ANTITHYROID DRUG ASSOCIATED HYPOPROTHROMBINEMIA},
  author={JamesJ. Lipsky and Mar{\'i}a Pilar Orgaz Gallego},
  journal={Drug Metabolism and Drug Interactions},
  year={1988},
  volume={6},
  pages={317 - 326}
}
  • J. Lipsky, M. Gallego
  • Published 1988
  • Biology, Medicine, Chemistry
  • Drug Metabolism and Drug Interactions
The thioamide class of antithyroid drugs has been associated with the development of hypoprothrombinemia. Two drugs in this class, propylthiouracil and methimazole, resemble the methyltetrazole-thiol leaving group of certain cephalosporin antibiotics. Both were found in vitro to inhibit the vitamin K dependent step in clotting factor synthesis, the gamma-carboxylation of glutamic acid with 50 per cent inhibitory concentrations of 2 mM for propylthiouracil and 0.1 mM for methimazole. Methimazole… 
View on PubMed
doi.org
9 Citations
Background Citations
2

Figures from this paper

9 Citations

Medical management of hyperthyroidism.
  • L. Trepanier
  • Medicine, Biology
    Clinical techniques in small animal practice
  • 2006
TLDR
All cats treated with methimazole should be monitored with BUN and creatinine, in addition to serum T4, complete blood count, and liver enzymes, and moderate to severe hypertension should be treated concurrently with-atenolol, amlodipine, or an ACE inhibitor.
Pharmacologic management of feline hyperthyroidism.
  • L. Trepanier
  • Medicine, Biology
    The Veterinary clinics of North America. Small animal practice
  • 2007
Cirrhosis‐induced pseudoglucagonoma syndrome in a patient with Type 2 Diabetes: an autopsy study
TLDR
It is worth noting that the patient suffered from irondeficiency anaemia already on initial presentation, indicating that pre-existing gastrointestinal disease may have contributed to the severe gastrointestinal haemorrhage following antithyroid treatment.
Long-term propylthiouracil use and acute myeloid leukemia: A case report and review of the literature
TLDR
A 31-year-old female who had been administered propylthiouracil for 15 years and shortly after delivery developed acute myeloid leukemia with complex karyotype, including a rare t(2;21) translocation.
Antithyroid medications and psychosis
TLDR
Patients who develop mental disorders while under ATD should be followed by an accurate evaluation of TSH, free triiodothyronine (FT3), and free thyroxine ( FT4) levels throughout the course of the psychiatric disease.
Severe gastrointestinal haemorrhage after methimazole intake
TLDR
A 65-year-old patient admitted to the emergency room (ER) for palpitations and readmitted to the ER for fatigue, tachycardia and melaena, where he was discharged on day 7, with the diagnosis of Graves’ disease.
Metal-induced B-H bond activation: reactions between half-sandwich Ir and Rh complexes with carboranylthioamide.
Novel half-sandwich metal (Ir, Rh) complexes constructed from carboranylthioamide ligands containing an unexpected metal-boron bond were synthesized and characterized. The strong base n-butyllithium…
Gene expression profiling in rat liver treated with various hepatotoxic-compounds inducing coagulopathy.
TLDR
It is concluded that these probe sets could be a good starting point in developing mechanism-based biomarkers for diagnosis or prognosis of hepatotoxicity-related coagulation abnormalities in the early stage of drug development.
Coagulopatías de las vías extrínseca y común

References

SHOWING 1-10 OF 17 REFERENCES
Antibiotic-associated hypoprothrombinemia: a review of prospective studies, 1966-1988.
TLDR
Patients at high risk for coagulopathy should be carefully monitored and serious consideration should be given to the use of prophylactic vitamin K in such cases, according to the hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia.
Deficiency of prothrombin and proconvertin after therapy with propylthiouracil.
TLDR
Observations on two patients have suggested a similarity between this apparently rare reaction to propylthiouracil and the therapeutic response to bishydroxycoumarin (Dicumarol), which appears to be a serious but little-known complication of the use of the latter drug.
Effect of N-methyl-thiotetrazole on vitamin K epoxide reductase.
Production of hypoprothrombinemia by moxalactam and 1-methyl-5-thiotetrazole in rats
To determine whether the hypoprothrombinemia associated with antibiotics containing a 1-methyl-5-thiotetrazole (MTT) group is a result of the presence of the MTT group, rats were maintained on a…
N-METHYL-THIO-TETRAZOLE INHIBITION OF THE GAMMA CARBOXYLATION OF GLUTAMIC ACID: POSSIBLE MECHANISM FOR ANTIBIOTIC-ASSOCIATED HYPOPROTHROMBINAEMIA
Mechanism of the inhibition of the gamma-carboxylation of glutamic acid by N-methylthiotetrazole-containing antibiotics.
  • J. Lipsky
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1984
TLDR
The in vitro observations presented here and a closer examination of the clinical evidence raise the possibility that MTT-containing antibiotic-induced hypoprothrombinemia may not be a vitamin K reversible phenomenon and suggest that a slowly formed metabolite of MTT may be directly responsible for the observed inhibition.
Partial sequence of rat prothrombin and the activity of two related pentapeptides as substrates for the vitamin K‐dependent carboxylase system
Hypoprothrombinemia following the use of propylthiouracil: case report.
  • G. Mirrer
  • Medicine
    Annals of internal medicine
  • 1955
Excerpt The most frequent toxic manifestations in the clinical use of propylthiouracil include drug fever, dermatitis, agranulocytosis and leukopenia. Severe hypoprothrombinemia following propylthi...
Hydro, oxido and other derivatives of vitamin K1 and related compounds.
Clindamycinに対する Bacteroides fragilis の耐性獲得に関する研究第1報:Clindamycin服用による糞便内のClindamycin耐性 Bacteroides fragilis の出現
...
...