Thyroid drugs Flashcards
What are the three approaches to treatment of hyperthyroidism
Interfere with thyroid hormone production
Modify tissue response to thyroid hormone
Destroy thyroid gland via radiation or surgery
Name the nine classes of drugs used to tx hyperthyroidism
Iodide uptake inhibitors (anion inhibitors) Inorganic Iodide Radioactive Iodine Thioamides Beta-adrenergic Antagonists Radiocontrast agents Corticosteroids Lithium Amiodarone
Name the three Iodide uptake inhibitors and its MOA
Thiocyanate
Perchlorate
Pertechnetate
- competes with iodid for uptake into the thyroid gland follicular cells
- causes aplastic anemia, so use is limited
Name the inorganic iodide used to treat hyperthyroidism and it’s MOA
Lugol’s solution
MOA is to cause Wolff-Chaikoff effect (high concentration of iodide inhibits T4/T3 synthesis/release via negative feedback loop)
Lugol’s solution works in three ways by
inhibiting iodide organification (oxidation)
inhibiting release of thyroid hormones
decreasing the size and vascularity of enlarged thyroid gland for easier surgical excision
In order for the autoregulatory phenomenon of Wolff-Chaikoff effect to work, what pathway must be intact
negative feedback loop
*usually the case thyroid dysfunction not previously treated
What are the five disadvantages of administering Lugol’s solution
Increases the intraglandular stores of iodine
- delays onset of thionamide therapy
- delays radioactive treatment
Must be used with other therapies
-gland can “escape” from iodide block to produce severe thyrotoxicosis
Crosses placenta
- can cause fetal goiter in large doses adminisitered over prolonged times
- avoid in pregnancy
Irritating and destructive to mucosa
Causes Jod-Basedow phenomenon
What is the Jod-Basedow phenomenon
Hyperthyroidism following administration of iodine or iodide which could lead to thyrotoicosis in people who have thryoid abnormalities that cause the gland to function without the control of the pituitary.
*The Jod-Basedow effect does not occur in persons with normal thyroid glands who ingest extra iodine in any form.
What is the difference between Wolff-Chaikoff effect and Jod-Basedow phenomenon
some ways the Jod-Basedow phenomenon is the opposite of the Wolff-Chaikoff effect, which refers to the short period of thyroid-hormone suppression which happens in normal persons and in persons with thyroid disease, when comparatively large quantities of iodine or iodide are ingested. However, unlike the Wolff-Chaikoff effect, the Jod-Basedow effect does not occur in persons with normal thyroid glands, as thyroid hormone synthesis and release in normal persons is controlled by pituitary TSH secretion, which does not allow hyperhyroidism when extra iodine is ingested.
Radioactive Iodine is used to treat
thyrotoxicosis
Radioactive iodine’s MOA includes
Rapid absorption and concentration by the thyroid, and incorporation into storage follicles
*the thyroid tissue is destroyed within a few weeks
What is the goal of radioactive iodine
to administer enough to result in Euthyroid state without precipitating hypothyroidism
Radioactive iodine can only be used in adults of what age
> 35 years of age
Radioactive iodine is not used in which patient population
pregnant or nursing mothers
The incidence of hypothyroidism after 2 years and 10 years of therapy include
after 2 years up to 30%
after 10 years up to 50%
Name the two thioamides used to treat hyperthyroidism
Prophylthiouracil (PTU)
Methimazole (Tapazole)
What is the MOA of the PTU and Methimazole
Binds to thyroid-peroxidase thereby inhibiting iodine organification and synthesis of thyroid hormones
prevents coupling of iodotyrosines (DIT)
What additional MOA does PTU have that Methimazole lacks
PTU also inhibits the peripheral conversion of T4 to T3, unlike methimaxole
Name four other drugs whose MOA is similar to PTU (inhibition of T4 to T3)
Sodium Thiopental (induction agent)
Propanolol (beta adrenergic antagonist)
Mifepristone (steroid receptor antagonist used to tx cushing’s syndrome)
Sodium Ipodate (radiocontrast agent used in ERCP procedures)
Does the thioamides (PTU/Mehtimazole) inhibit the release of stored thyroid hormones
NO
What is the major SE associated with PTU/Methimazole administration
Pruritic rash with fever
What is the most life-threatening SE associated with PTU/Methimazole adminsistraton
Severe agranulocytosis (lowered WBC) bleeding tendancies
PTU/Methimazole and pregnacy
Both drugs cross the placenta and will effect the fetal thyroid
- however, PTU is preferred bc it is more highly protein bound and crosses placental less
- Okay to breast feed
Thioamides are sometimes referred to as?
Goitrogen
*as TSH levels rise in response to lowered thyroid hormone levels, the thyroid gland hypertrophies
Name the main beta-adrenergic antagonist used to tx hyperthyroidism
Propanolol
What is the MOA of beta-adrenergic antagonists
Decreases the peripheral conversion of T4 to T3
*decreases the symptoms of excess sympathetic activity (tachy, tremor, anxiety, sweating, and heat intolerance)
beta-adrenergic antagonists must be used with caution in which patient population
CHF
Reactive airway disease
What is the MOA of corticosteroids
inhibits the 5’-deiodinase enzyme that converts T4 to T3, reducing net thyroid activity.
What is the MOA of Lithium
inhibits thyroid hormone release from thyroid follicular cells, as well as inhibition of synthesis
What antidysrhythmic resembles thyroxine
amiodarone
*contains a large amount of iodine that accumulates in the thyroid when metabolized
What percent of patients taking amiodarone will develop thyroid dysregulation
14-18%
Amiodarone can cause ——- and ——-
hypothyroidism
hyperthyroidism
The hypothyroidism caused by amiodarone is a result of what effect
wolff-chaikoff
*increased iodine concentration leads to decreased T3/T4 via upregulation of negative feedback loop
the hyperthyroidism caused by amiodarone is a result of what phenomenon that is classified as type 1
jod-basedow- iodine-induced hyperthyroidism
*Increased concentration of Iodine leads to increased T4/T3
The hyperthyroidism caused be amiodarone is categorized as two types, what is the main difference between the two types
type 1: doppler shows INCREASED vascularity of gland
type 2: doppler shows DECREASED vascularity of gland
*known as destructive thyroiditis
Hypothyroidism is classifed as
primary, secondary, tertiary, and thyroid gland hormone deficiency
Hashimoto’s thyroidits is classified as what type of hypothyroidism
primary
*destructive autoantibodies Destroy the thyroid gland
VS.
* Grave’s disease whereby autoantibodies bind to the gland and stimulate thyroid hormone production
What significant consideration must be kept in mind when deciding to tx hypothyroidism
replacement must be weighed against the risk of percipitating myocardial ischemia
What main drug is used to treat hypothyroidism
Levothyroxine (T4)
Why is Levothyroxine the most commonly used thyroid supplement
Because its GI absorption is predictable up to 75%
