E4: Thyroid Drugs Flashcards
Drugs of this section are primarily aimed towards treating what conditions?
Hypothyroidism & Hyperthyroidism
What are the synthetic thyroid Hormones discussed in the treatment of Hypothyroidism?
What are their characteristics?
Potency; Bioavailability; t1/2; Daily Doses
Hypothyroidism is treated through hormone replacement therapy
Levothyroxine (T4) & Liothyronine (T3)
Relative Potency: 1; 4
Bioavailability:80%; 95%
t1/2: 7days; 1day
Daily Doses: 1; 1-3
Describe how Thyroid hormone is synthesized
- Iodide is accumulated by thyroid follicular cells by the sodium/iodide symporter
- [Thyroperoxidase] catalyzes:
- Iodination of tyrosine residues of thyroglobulin
- Coupling of iodotyrosines to form triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)
- Thyroglobulin is stored as colloid in thyroid follicles
- Thyroglobulin undergoes proteolysis to release T4 and T3 when stimulated by thyroid-stimulating hormone (TSH) aka thyrotropin
Thioamide drugs
How do they work?
Examples?
Thioamide drugs inhibit [Thyroperoxidase], thereby inhibiting the synthesis of thyroid hormones.
Ex. Methimazole & propylthiouracil
How do elevated iodide levels & lithium affect Thyroid hormone synthesis
Elevated iodide concentrations and lithium inhibit the proteolysis & release of thyroid hormones
Which factors stimulate Thyrotropin-Releasing hormone release?
Which inhibit it?
Stimulatory:
- Cold
- Acute psychosis
- Circadian & pulsatile rhythms
Inhibitory:
- Severe Stress
What signal transduction pathway do thyroid hormones use?
Hormonal signaling
Thyroid hormones activate cytoplasmic receptors which are translocated to the cell nucleus
In the nucleus, they activate gene transcription and thereby increase the metabolic rate and accelerate a wide range of cellular activities required for normal growth and development and for the maintenance of normal metabolism
Describe the treatment plan of Hypothyroidism
Hypothyroidism: Replacement Therapy
Levothyroxine (synthetic T4) is the drug of choice
It has a long half-life (7 days) and can be administered orally once a day.
Liothyronine (synthetic T3) is more potent than levothyroxine and has a higher oral bioavailability.
It has a shorter half-life, however, and may need to be given several times a day.
Which drug types are used in the treatment of Hyperthyroidism?
- Thioamides: Methimazole & PTU
- β-Adrenoceptor antagonists
- Potassium Iodide Solutions
- RAI (131I)
What is the purpose of Thioamide drugs in the treatment of Hyperthyroidism?
Thioamide drugs (Methimazole and PTU)
- Inhibit thyroperoxidase-catalyzed steps in the synthesis of thyroid hormone
- PTU also inhibits the peripheral conversion of T4 to T3
- Onset of action of these drugs is delayed because of the time required to deplete glandular stores of thyroid hormone
- Used in an attempt to induce remission or as a means to control symptoms before surgery or RAI treatment in patients with Graves disease
What is the purpose of B-Adrenoceptor Antagonists in the treatment of Hyperthyroidism?
β-Adrenoceptor antagonists:
Used to control the cardiovascular symptoms of hyperthyroidism in patients who are;
- Suffering from acute thyrotoxicosis
- Awaiting surgery
- Awaiting a response to RAI treatment.
What is the purpose of Potassium Iodide solutions in the treatment of Hyperthyroidism?
Potassium Iodide Solutions:
Potassium Iodide solutions
Used to;
- •Control symptoms of acute thyrotoxicosis
- •Reduce the vascularity and size of the thyroid gland before surgery
- •Inhibit thyroid hormone release following RAI treatment
MoA:
- •Iodide salts present act rapidly to inhibit the release of thyroid hormones from the thyroid gland
- •Improves symptoms in 2-7 days as thyroid hormone levels decline
How does RAI (131I) effect Thyroid Hormone?
RAI (131I)
- Concentrated by the thyroid gland and emits β-particles that destroy thyroid tissue
- Used in the treatment of Graves disease & other forms of hyperthyroidism
- Absolutely contraindicated in pregnant women
Which drugs inhibit Thyroperoxidase?
Methimazole (tapazole) & Propylthiouracil (PTU)
