51 - antithyroidal drugs

Question 1

intro

Answer 1

thyroid gland:

thyroid hormone secretion regulation: TRH, TSH, TSH receptor, organification of iodine + production of TH

negative feedback loop: T3/T4 –> stop TRH/TSH

other regulators:
glucocorticoids –> stop TSH
estrogens –> stimulate TSH

Question 2

thyroid hormone synthesis

Answer 2

1. iodine into follicular cell :
   Na/I symporter (2Na + I into thyroid)
2. iodine into colloid: iodine oxidation by thyroid peroxidase (I- –> Io)
3. iodine attach tyrosine (organification) on thyroglobulin molecule:
   mono-iodotyrosine –> di-iodotyrosine
4. conjugation:
   T2+T2=T4
   T1+T2=T3
5. proteolysis:
   thyroglobulin –> T3/T4

Question 3

thyroid hormone - effects

Answer 3

growth:
- normal growth in children
- deficiency –> growth retardation

development:
- development of fetal + neonatal brain
- deficiency: impaired mental function

general - metabolism:
- increased metabolism in tissues
- increased BMR

lipid metabolism:
- TH up –> activation of fat mobilization –> increased FA in blood
TH –> increased oxidation of FA in tissues
TH –> increased CH + TAG conc.
increased LDL receptors

Carbohydrate metabolism:
- TH –> increased peripheral insulin sensitivity
- increased gluconeogenesis + glycogenolysis

CVS:
- increased HR + cardiac contractility + CO
- increased vasodilation
- increased B-receptors (SNS)

CNS:
- TH –> alternation of mental state
- decreased TH –> mentally sluggish
- increased TH –> stress + anxiety

reproductive system:
- normal reproduction
- effect on menstrual cycle

kidney:
- increased renal blood flow –> increased GFR
- increased RAAS
- increased B-receptors

Question 4

intro - thyroid hormone disorder

Answer 4

hyperthyroidism
hypothyroidism

Question 5

antithyroidal drugs - hyperthyroidism

Answer 5

1. interfere with synthesis
   - different levels: organification, oxidation, ionization, conversion T4–>T3 (5-deiodinase)
2. destruction with radiation + surgery
   - radio-labeled iodine –> increase iodine concentration –> impairment
   - remove thyroid
3. modify tissue response to thyroid hormones
   - peripherally acting agents –> modify tissue response
   - B-blockers (protect heart)

Question 6

thioamide

Answer 6

mechanism:
- competitive inhibitor of thyroid peroxidase
- decreased peripheral deiodination of T3/T4 (ONLY propylthiouracil)

indication:
- hyperthyroidism, thyrotoxicosis

SE:
allergic reaction (most common), agranulocytosis (reversible)

drugs:
- propylthiouracil, carbimazol, methimazole (most potent)
SLOW ONSET (3-4 weeks)