Antithyroid drugs ANJALI SAJI
Role of the Thyroid gland participates in normalizing growth and development and
energy levels and the proper functioning and maintenance of tissues / organs
critical for the nervous, skeletal and reproductive tissues it affects secretion and degradation rates of all hormones
Function of the Thyroid Gland secretion of the following hormones:
triiodothyronine (T3) ; 59% iodine tetraiodothyronine (T4; also known as
thyroxine); 65% iodine calcitonin
THYROID PHYSIOLOGY
Iodide Metabolism The recommended daily adult iodide (I-) intake is
150 mcg Biosynthesis of Thyroid Hormones Transport of Thyroid Hormones
thyroxine-binding globulin (TBG) about 0.04% of total T4 and 0.4% of T3 exist in
the free form.
Biosynthesis of thyroid hormones
Steps in Biosynthesis
Iodide trapping
Oxidation of iodide to iodine
Iodide Organification
Formation of T4 and T3
Release of T4 and T3
Peripheral metabolism of thyroid hormones The primary pathway for the peripheral metabolism of thyroxine (T4) is
deiodination deiodination of T4 may occur by monodeiodination of the outer ring, producing 3,5,3'-triiodothyronine (T3), which is three to four times more potent than T4
Anti-thyroid Drugs Thioamides
Iodides
radioactive iodine
Beta adrenoceptor blocking agents
Biosynthesis of thyroid hormones
Thioamides Methimazole Propylthiouracil (PTU) Carbimazole MOA:
inhibit synthesis by acting against iodide organification (both)
coupling of iodotyrosines (both) Blocks peripheral conversion of T4 to T3 (PTU)
Thioamides Pharmacokinetics:
almost completely absorbed in the GIT serum half life: 90mins(PTU) ; 6 hours (methimazole) excretion: kidney – 24 hours (PTU) ; 48 hours (Methimazole) can cross placental barrier (lesser with PTU) Methimazole 10x more potent than PTU PTU more protein-bound
Thioamide uses
Definitive therapy Graves disease Toxic nodular goitre
Preoperatively In thyrotoxic patients
Along with RAI PTU in hyperthyroidism in pregnancy
Thioamides Adverse Effects:
maculopapular rash benign transient leukopenia agranulocytosis hepatitis (PTU) ; cholestatic jaundice (Methimazole) vasculitis lupus-like syndrome
Iodine131
preparations: sodium iodide 131
MOA: trapped within the gland and enter intracellularly and delivers strong beta radiations destroying follicular cells
Penetration range-400-2000µm Clinical uses: Grave’s,
primary inoperable thyroid CA Contraindication: pregnancy
Iodine131
Advantages Easy administration Effectiveness Low expense Absence of pain
Iodine131
Thioamides should be given initially and stop 5-7 days before radioactive iodine administration
131I dosage generally ranges between 80-120uCi/g of estimated thyroid wt. corrected for uptake. May be repeated after 6 months
Adverse effects permanent hypothyroidism potential for genetic damage may precipitate thyroid crisis
Anion Inhibitors Monovalent anions such as
perchlorates, pertechnetate and thiocyanate can block uptake of iodide by the gland by competitive inhibition
can be overcome by large doses of iodides useful for iodide-induced hyperthyroidism
(amiodarone-induced hyperthyroidism) rarely used due to its association with
aplastic anemia
Inorganic Iodines major anti-thyroids before the
introduction of thioamides (1950s) preparations:
strong iodine solution (Lugol’s) potassium iodide iodone
Inorganic Iodines MOA:
acutely blocks release of thyroid hormone from the gland by inhibiting thyroglobulin proteolysis
inhibit iodide organification Uses:
useful in thyroid storms: 2-7 days Preoperatively - iodides decrease vascularity, size
and fragility of hyperplastic gland Caution:
it may delay onset of thioamide effects; should be given after initiation of thioamides
Iodinated Contrast Media Iodinated contrast media Ipodate (oral) Iopanoic acid (oral) Diatrizoate (intravenous) valuable in hyperthyroidism (but is not
labeled for this indication) MOA: inhibits conversion of T4 to T3 in the liver,
kidney, brain and pituitary Another MOA is due to inhibition of
hormone release secondary to iodide levels in blood
Useful in thyroid storms (adjunctive therapy)
Beta Blockers Drugs: Propranolol,esmolol, Atenolol MOA:
Membrane-stabilizing action: inhibits T4 to T3
Ameliorate symptoms – tremor,palpitation,anxiety secondary to increased circulating catecholamines by blocking beta receptors
Indications: Grave’s, Thyroid storm
Corticosteroids gain rapid control of hypermetabolic effects of peripheral
T4 and T3 Methyl Prednisolone iv is given for patients with Grave’s
ophthalmopathy 1mg/kg/day (60mg/day 3 divided doses); if it should be
given for more than 4 weeks, taper to decrease risk of adrenal crisis
Thyroid storm
Sudden exacerbation of thyrotoxic symptoms Life threatening condition Vigorous management
Propanalol 1-2mg i/v or 40-80mg PO Q6h Diltiazem 90-120mg Po Q8-6 hrs or 5-10mgs
intravenous infusion/hour
Thyroid storm
Potassium iodide Propylthiouracil Hydrocortisone
Supportive therapy Plasmapheresis/peritoneal dialysis
Hyperthyroidism and Pregnancy
Ideal situation- treat before pregnancy Pregnancy-Radioactive iodine CI Propylthiouracil
Dose limitation≤ 300mgs/day Methimazole alternative- fetal scalp defects
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