Thyroid & Antithyroid Drugs Flashcards
What are the general functions of thyroid hormones?
Growth and development
increased body temperature
Increased energy metabolism
What protein facilitates iodide uptake into thyroid gland?
Sodium/iodide symporter (NIS)
Describe path and modification of iodide from blood stream to T3 or T4
Iodide taken up by NIS into follicular cell
Converted within cell to Iodine by peroxidase
Diffuse into colloid?
Attached to tyrosine residues to form MITs and DITs
MITs and DITs combined to form T3 and T4
Which form of thyroid hormone is the active form?
T3
Which molecule is predominately secreted?
T4 (5:1 ratio)
In what form are T3, T4 present in the blood?
Majority bound to thyroxine-binding-globulin (TBG)
Describe thyroid hormone secretion.
Thyroglobulin is phago-/pinocytosed, degraded and released from follicular cell
Where is the T3 receptor and what is its function in ABSENCE of thyroid hormone?
Homo-dimer bound to TRE (thyroid response element)
Inhibits gene expression with co-repressors
Where is the T3 receptor and what is its function in PRESENCE of thyroid hormone?
T3 binds to receptor in the nucleus (T4 is converted to T3, then enters.)
Co-repressors, and 1 thyroid receptor dissociate, and are replaced with RXR; now increased gene transcription
What effect does TRH have on thyroid hormone synthesis? Regulation?
TRH promotes TSH release by pitiutary
Both hypothalamus and pituitary have negative feedback from T3, T4.
“High” serum iodide inhibits thyroid hormone synthesis in the short term
“low” iodide promotes thyroid synthesis (also short term?)
Effects of thyroid hormone on SNS?
Increase beta receptors
Decrease alpha receptors
Effects of thyroid hormone on growth and development
Brain development
Activation of osteoclasts, osteoblasts
Effect of thyroid hormone on Respiratory system
increase tissue O2 consumption, increases Co2 formation
RR increases
Effect on GI
increase secretions and motility
Effect on CNS
think faster, affect muscle tone
Effect on Skin and Hair
promote skin, hair, nail growth
Prevent glycosaminoglycan accumulation (myxedema)
Effect on CV
Increase HR
increase inotropy/contractility
Increase cardiac output
Decrease vascular resistance
Metabolic effects
Decrease circulating faat
Increase carb absorption, glycolysis, insulin secretion
Increase protein synthesis and breakdown (?)
Increased need for vitamins and cofactors
Increased basal metabolic rate
Signs of hypothyroidism
Bradycardia
Slow bone growth/MR
Fatigue, hypokinetic muscles
Myxedema
Dry scaly skin, depressed hair and nail growth
Increased body weight, atherosclerosis, cold intolerance
Signs of hyperthyroidism
Tachycardia, sweating, tremors
High respiratory rate, possible failure
Anxiety, nervous, worry, paranoia, restlessness
Diarrhea
Exophthalmos, sweating
Decreased body weight, increased appetite
Causes of hypothyroidism?
Primary and secondary
Primary:
- Congenital underdeveloped thyroid
- Autoimmine thyroiditis (Hashimoto’s)
- Iodide deficiency
- Surgery/radiation
Secondary:
- impaired TSH production secondary to ICP, neoplasm, irradiation, surgery
Treatment of hypothyroidism
Hormone replacement with synthetic hormone
Levothyroxine
MoA, pharmacokinetics
T4 analogue, activates T3 receptors
adverse effects: hyperthyroid sx
longer half-life, higher oral absorption than T3 analogue
Liothyronine
MoA, pharmacokinetics
T3 analogue, acts on T3 receptors
Adverse effects similar to other synthetic thyroid hormones
Shorter half-life, higher oral absorption, very potent!
