Thyroid and Antithyroid Drugs Flashcards
Synthesis and Transport of Thyroid Hormones
TRANSPORT
iodide ion is converted to iodine by thyroid peroxidase (TPO)
IODINE ORGANIFICATION
tyrosine residues in thyroglobulin are iodinated to form monoiodotyrosine (MIT) or diiodotyrosine (DIT)
COUPLING
2 molecules of DIT to form T4
1 molecule of each MIT and DIT to form T3
PROTEOLYSIS
T4 and T3 released from the thyroid and transported in the blood by thyroxine binding globulin (TBG)
Thyroid Hormones for Hypothyroidism
maximum effect seen after 6-8 weeks of therapy
Levothyroxine - T4
Liothyronine - T3
Liotrix and Thyroid USP - 4:1
Thyroglobulin - 2:1
Medical emergency representing the end state of untreated hypothyroidism
progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock and death
Myxedema Coma
TREATMENT:
Levothyroxine - 300 -400 mcg followed by 50-100 mcg daily
Treatment of Myxedema Coma
IV loading dose of Levothyroxine (300 - 400 mcg) followed by 50-100 mcg daily
IV hydrocortisone - if patient has associated adrenal or pituitary insufficiency
Inhibits thyroid peroxidase reactions
Blocks iodine organification
(-) peripheral conversion of T4 into T3
THIOAMIDES
Propylthiouracil
Side effects of Propylthiouracil
maculopapular pruritic rash
FULMINANT HEPATITIS
AGRANULOCYTOSIS
Lupus like syndrome
Inhibits thyroid peroxidase reactions
Blocks iodine organification
THIOAMIDES
Methimazole
Carbimazole
Preferable during the 1st trimester of pregnancy, thyroid storm and those experiencing adverse reactions to methimazole
Propylthiouracil
DOC for nonpregnant hyperthyroid px because of longer DOA (24 h)
Methimazole
Side effects of Methimazole
aplasia cutis congenita
choanal atresia
esophageal atresia
The mainstay of the treatment of postpartum hyperthyroidism in particular during lactation
Methimazole
Acute severe neutropenia
Heralded by SORE THROAT or HIGH FEVER
Increased susceptibility to infections
AGRANULOCYTOSIS
discontinue PTU or methimazole
administer recombinant G-CSF (Filgrastin) to accelerate recovery
treat w/ prophylactic broad-spectrum antibiotics
(-) iodide uptake (trapping)
INORGANIC ANIONS
K Perchlorate
K Thiocyanate
HIGHLY TOXIC
(-) iodine organification and hormone release
reduce size and vascularity of thyroid gland
improvement in thyrotoxic symptoms occurs rapidly - 2-7 days
IODIDE
Lugol’s solution
Potassium Iodide
Potassium Iodide Saturated Solution (KISS)
Side effects of Iodides
iodinism
acneiform rash
metallic tase
Ingestion of IODINE causes HYPOthyroidism
Wolf-Chaikoff effect
Ingestion of IODINE causes HYPERthyroidism
Jod-Basedow effect
(-) peripheral conversion
(-) deiodinase
(-) proteolysis
RADIOCONTRAST DYES
Ipodate
Iopanoic Acid
control HR and other cardiac abnormalities of severe thyrotoxicosis
(-) peripheral conversion of T4 into T3
cause clinical improvement WITHOUT altering thyroid hormone levels
BETA BLOCKERS
Propranolol
Esmolol
Metoprolol
Atenolol
May be used to treat thyrotoxicosis-related arrhythmias
Esmolol
Emits beta rays causing destruction of thyroid parenchyma
Patients should be EUTHYROID or on BETA BLOCKERS before RAI
Onset of action - 6-12 weeks
Maximum effect - 3-6 mos
Radioactive Iodine 131
Preferred treatment for most patients
Permanent cure of thyrotoxicosis w/o surgery and no effect on other tissues
Radioactive Iodine 131
Sudden acute exacerbation of all of the symptoms of thyrotoxicosis presenting as a life threatening syndrome
Thyroid Storm
Treatment for Thyroid Storm
Propylthiouracil (PTU) - blocks thyroid hormone synthesis
Iodides (SSKI) - retards release of thyroid hormones
Propranolol - controls severe cardiovascular manifestations
Hydrocortisone - protects against shock and also blocks peripheral conversion of T4-T3
