Thyroid and Anti-Thyroid Drugs Flashcards
What is the role of follicular cells and parafollicular cells of the thyroid gland?
Follicular Cell: secretes the thyroid hormones
Parafollicular Cell: Secretes Calcitonin
What is the function of the thyroid gland?
Take up iodine and convert it into thyroid hormones
What is the iodine pathway?
Covalently bound to tyrosine residues in the thyroglobulin molecules via thyroperoxidase
–peroxidase enzymes are responsible for oxidationg, organification, and in addition to iodide coupling reactions of MIT and DIT
MIT + DIT = triiodothyronine (referred to as T3)
DIT + DIT = Thyroxine (referred to as T4)
Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3
What is reverse triiodothyroine (reverse T3 or rT3)?
Isomer of T3
- –derived from T4 through the action of deiodinase
- -clinically silent, may come about during stressful situations
What are the physiological effects of Thyroxine (T4)?
- Increases BMR via Na/K ATPase activity (increase in RR, body temp and O2 consumption)
- Potentiates the effects of catecholamines (increases sympathetic activity of beta effects) – increase in CO and HR
- Promotes brain (CNS) development
- Promotes bone growth synergistically with GH
- Increases gluconeogensis, glycogenolysis and lyposis
- LDL receptors expression: decrease in hypothyrodism and increase in hyperthyroidism
What are the Pharmacokinetics of thyroid hormones?
Most circulating T3 is formed from deiodination of T4 in the peripheral tissue, liver, kidney
- -this enzyme also present in pituitary gland, brain and in brown fat
- -some T3 is released from thyroid
Explain the role of Thyroxin-Binding Protein (TBG) – which is a transport protein for T3 and T4
TBG decreased in hepatic failure and increased in pregnancy and oral contraceptive pills (OCP)
–normal thyroid gland produces over 90% of T4 and about 10% T3
–T3 has a greater affinity to receptors so therefore it is much more potent than T4
Only free forms of T3 and T4 are active
What are the physiological controls of thyroid gland?
The pituitary gland is regulated by hypothalamus (TRH)
- -thyroid gland is under the control of the pituitary gland (TSH)
- -negative feedback is from T3 and T4 to the hypothalamus and pituitary gland
what factors affect the hypothalamus- pituitary axis?
Hypothalamus: stimulating — cold, acute psychosis, circadian and pulsatile rhythms ; inhibitory – severe stress
On TRH: inhibitory are corticoids/dopamine and somato-statin
What is the mechanism of action of thyroid hormones?
Signaling mechanism is via TRH-IP3 mediated ; TSH-cAMP mediated and the T3 and T4 binds with the receptor in the nucleus
- -binds with intracellular receptors that control the gene expression with RNA formation and protein synthesis
- -protein synthesized depends on tissues involved (Na/K ATPase in the and Beta 1 receptor in the heart)
What are the two thyroid hormones?
Thyroxine (T4)
Triiodothyronine (T3)
What are the various thyroid hormone preparations?
- Levothyroxine (T4) longer half life (T4 is converted to T3 in target tissues such as liver, kidneys, etc)
- Liothyronine (T3) short half life ( T3 is 10 x more potent than T4)
Uses:
–cretinism (due to thyroid hormone synthesis enzyme defect) , adult hypothyroidism (myxedema)
AE: tremors, tachy, arrhythmias, and heat intolerance
P450 enzymes induction can increase the metabolism of the thyroid hormones (T3 and T4), what drugs induce P450 enzymes?
Rifampin
Phenobarbital
Phenytoin
What are the primary, secondary and tertiary causes of hypothyroidism?
Primary (Thyroid): Hashimoto’s Thyroiditis (an autoimmune disorder) — anti - TPO (thyroperoxidase)
–causes radiation exposure, iodine deficiency, inadequate supplementation, drugs (lithium and aminodarone)
Secondary (Pituitary): Decreased TSH due to radiation, surgery or tumor
Tertiary (hypothalamus): Decreased TRH production
How is dx made for hypothyroidism?
Increased TSH (if primary), decreased Total T4 , decreased free T4 and decreased T3 in blood