Drugs for Thyroid Disorders Flashcards
what class are these drugs:
Levothyroxine
Liothyronine
Liotrix
Thyroid hormone preparations
what class are these drugs:
Thioamide drugs
Methimazole
Propylthiouracil
Antithyroid agents
what enzyme converts T4–>T3/rT3
DEIODINASE
Thyroid hormones carried in blood primarily by
TBG
Thyroid hormones carried in blood primarily by
TBG
which is more potent T3 or T4
T3 about 5X more potent than T4
why is Thyroperxidase very important enzyme?
Involved in three different steps in thyroid hormone synthesis
More efficient at combining DIT than MIT, thus more T4 released than T3
Very good drug target
what are 3 functions (in order ) of thyroperoxidase (TPO)
Thyroperoxidase oxidizes I- to I2 and transports it into the follicular lumen
Thyroperoxidase couples I2 to tyrosine residues present on thyroglobulin (organification), forms MIT and DIT
Thyroperoxidase couples MIT and DIT residues to form T3 and T4
how is iodide conserved inn thyroid hormone synthesis
Thyroglobulin is broken down by lysosomes, releasing T3 and T4 into the bloodstream; MIT and DIT are broken down by deiodinase and the iodide is conserved
MOA of Levothyroxine (Synthetic T4)
Nuclear receptor –> Thyroid Receptor with Retinoid X Receptor –>Gene transcription –> Growth, development, and calorigenesis
Stable composition leads to consistent and predictable blood levels
Few allergic reactions, Once-daily dosing
Adverse effects of Levothyroxine (Synthetic T4)
Tachycardia, heat intolerance, tremors, arrhythmias
Adverse effects of Levothyroxine (Synthetic T4)
- Coffee, fiber, soya products, aluminum hydroxide, calcium supplements, cholestyramine, ferrous sulfate, sucralfate –> Reduce absorption
- Estrogens, androgens, glucocorticoids alter TBG and TOTAL T3 and T4 levels [Free form is normal]
Liothyronine (Synthetic T3)
difference vs synthetic T4
More potent and greater bioavailability than levothyroxine but seldom used
Shorter half-life
Does not affect plasma T4 levels
More cardiovascular effects
More expensive
May be used when rapid onset or termination of action is desired
determine DX:
End-stage result of untreated hypothyroidism
Progressive weakness, stupor, hypoventilation, hypothermia
Elderly patients with underlying vascular and pulmonary disease
myxedema coma
myxedema coma RX:
Intubation with mechanical ventilation
Loading dose of IV thyroxine, followed by maintenance dosing
Add liothyronine if response is suboptimal
what are the 5 classifications of antithyroid drugs
Thioamide drugs
Beta adrenoceptor antagonists
Iodide salts
Perchlorate
Radioactive Iodine I-131
CLASSIFICATION AND MOA of Propylthiouracil (PTU)
thioamides
Inhibit thyroperoxidase –> inhibits organification & coupling
Also inhibits peripheral conversion of T4 to T3
Highly protein bound
It is choice in 1st trimester of pregnancy
what is drug of choice in 1st trimester of pregnancy
PTU- propylthiouracil
what is drug of choice in 2nd/3rd trimester of pregnancy
Inhibit thyroperoxidase –> inhibits organification & coupling
long half life, less hepatotoxic
No effect on peripheral deiodinase
No plasma protein binding
Crosses placenta; 3X incidence of birth defects
It can be used in 2nd and 3rd trimester of pregnancy otherwise cause aplasia cutis, esophageal atresia, etc
Excessive treatment with either _____,______ in pregnant women can cause cretinism – monitor T4 levels carefully
Propylthiouracil (PTU)
Methimazole
what is the drug of choice for Antithyroid Drugs: β- Adrenoceptor Blockers
Propranolol
MOA of Propranolol
Hyperthyroidism increased beta-adrenergic receptors
Manage cardiovascular symptoms of thyrotoxicosis
Tachycardia, palpitations, sweating, tremor, heat intolerance, hyperreflexia, and arrhythmias
Inhibition of peripheral conversion of T4 to T3
uses for propanolol
thyroid storm
adverse effects for propanolol
Hypotension, bradycardia, AV blockade
what is the drug classification for the following drugs:
thiocyanate, perchlorate, fluoroborate, lithium
ionic inhibitors
MOA of ionic inhibitors
Interfere with concentration of iodide by thyroid gland
specific MOA of Perchlorate, fluoroborate
Inhibits sodium-iodine symporter, blocks iodide uptake at step 2
Grave’s disease and amiodarone induced thyrotoxicosis
Cause fatal aplastic anemia
MOA of Potassium Iodide, Lugol’s Solution
Inhibit iodide organification and hormone release
Reduce size and vascularity of thyroid gland prior to thyroidectomy
Wolf-Chaikoff effect —> hypothyroidism
Jod basedow phenomenon —-> hyperthyroidism
USES of Potassium Iodide, Lugol’s Solution
Pre-thyroidectomy & Post RAI treatment
Prophylaxis in case of nuclear accidents or following RAI treatment
Potassium iodide competitively inhibits thyroid uptake of radioactive isotopes –> prevent the development of thyroid carcinoma
which antithyroid drug is the only isotope used for treatment of thyrotoxicosis (Others are used in diagnosis
Radioactive Iodine (131I)
MOA of Radioactive Iodine (131I)
Emits β-particles –> destroy thyroid tissue
uses of Radioactive Iodine (131I)
Treatment of hyperthyroidism (Graves disease, toxic nodular goiter, hyperthyroidism in older patients and in those with heart disease)
Diagnosis of disorders of thyroid function
Contraindications for 131 I
ABSOLUTE CI IN PREGNANCY
Contraindications for 131 I
ABSOLUTE CI IN PREGNANCY
list some advantages of Radioactive Iodine (131I):
Spare the risks and discomfort of surgery
Cost is low
Hospitalization is not required
Patients can participate in their customary activities during the entire procedure
list some disadvantages of Radioactive Iodine (131I)
High incidence of delayed hypothyroidism
Significant increase in specific types of cancer, including stomach, kidney, and breast.
Can induce a radiation thyroiditis
The three primary methods for controlling hyperthyroidism are:
Antithyroid drug therapy
Destruction of the gland with radioactive iodine
Surgical thyroidectomy
what is the management of Graves’ Disease
Methimazole (preferred) or propylthiouracil is administered until the disease undergoes spontaneous remission.
why is Methimazole is preferable to propylthiouracil for managment in graves disease
(except in pregnancy and thyroid storm) because it has a lower risk of serious liver injury and can be administered once daily, which may improve adherence.
RX. for Thyroid Storm
Propranolol
PTU
Potassium iodide
Supportive therapy
Toxic multinodular goiter is usually associated with a large goiter and is best treated by preparation with _____(preferable) or __________ followed by subtotal thyroidectomy.
methimazole or propylthiouracil
Pharmacology of Toxic Adenoma
-RAI treatment destroys adenoma and spares contralateral gland (uptake suppressed by low TSH)
-Patients usually end up euthyroid
-Thioamides may be used to suppress symptoms prior to RAI
adverse effects of: Propylthiouracil (PTU) &
Methimazole
Nausea, gastrointestinal disturbances, rash, agranulocytosis, hepatitis (PTU-warning), hypothyroidism
adverse effects of: Radioactive iodine (131I) (RAI)
Sore throat, hypothyroidism
adverse effect for propanolol
Asthma, AV blockade, hypotension, bradycardia
