Thyroid/Antithyroid Agents Flashcards
How do TSH and methimazole affect the thyroid hormone synthesis pathway?
Methimazole: this is an antithyroid agent that blocks the transport of iodide
TSH: stimulates all steps involved in T4 synthesis pathway
What are the roles of TSH, TRH, iodine, and antibodies to TSH receptors in the regulation of thyroid hormone secretion?
TSH: Stimulates all steps involved in T2 synthesis pathway
TRH: Stimulates the release of TSH and prolactin by anterior pituitary
Iodide: Needed for synthesis
TSH-R(AB): activates TSH receptors, which increases T3 and T4 secretion and causes hyperthyroidism (Humans)
What effects do different stressor (ie cold) have on thyroid hormone secretion?
Increased TRH = Increased TSH = Increased T4
What are the three major carriers of T3 and T4 in circulation?
Thyroxine binding globulin: high affinity low capacity
Prealbumin
Albumin
T/F Throxine binding globulin is 4x higher in humans than it is in dogs and is not found in cats, rabbits, or birds
TRUE
What do cats, rabbits, and birds use to bind T3 and T4?
Transthyretin (Prealbumin)
In humans, what % of T4 and T3 is bound by plasma proteins. Is this higher or lower in dogs?
T4 = 99.98%
T3 = 99.8%
Dogs = lower, about 99%
T/F when treating a dog with hypothyroidism, a human dose will usually treat them
FALSE
Why can you not treat dogs with hypothyroidism with human levels of T4?
It is too low; the half life of T4 in dogs is 8-16 hours, while it is 7 days in humans
How are thyroid hormones excreted/
Conjugates enter the bile and into the gut where they are removed via feces
What are some factors that can affect plasma protein levels and binding?
Estrogen = Increase TBG synthesis
Liver and kidney dz = decreased half-life
NSADIS and CNS drugs = competition for albumin binding sites to free T3 and T4
What is the fate of most of the T4 in the system?
50% –> rT3
30-40% –> T3
15-20% –> Conjugates in liver
Where is Type I deiodinase found?
Liver and kidney
Transformation from T3 and T4
Where is Type II deiodinase found? What does it do?
Deiodinates T4
Brain, pituitary, and brown fat
Where is Type 3 deiodinase found and why is it important?
Placenta and brain
Fetus is surrounded by the placenta. Fetus has a lot of T3 so it is a way to control it and save the mom
What increases the rate of T4 to T3 conversion?
Hypothyroidism
Hyperthyroidism causes a decreased rate of T4 –> T3
What is the current perspective regarding the cold temperature on calorigenesis?
Cold > increased EPI, NE > increased Type 2 deiodinase > increased T3 > increased uncoupling protein in mitochondria > generates heat
Where are a large number of mitochondria with uncoupling proteins located?
Brown fat cells; located between scapulas, in thorax, and abdomen
What is the action of thyroid hormones on growth and development?
Increases GH secretion and action; shortage of this can lead to cretinism.
Critical for development and maintenance of neural tissues
What is the action of thyroid hormones on calorigenesis?
Increase in heat generation and oxygen consumption
What is the action of thyroid hormones on CV system?
Increased CO needed to keep up with an increased oxygen consumption
What is the action of thyroid hormone on lipid metabolism?
Facilitation of the effect of the lipolytic hormones
Increased conversion into bile acids
What dermatologic effects does the thyroid hormones have?
They are needed for hair and skin turnover
See alopecia in hyperthyroidism
What effects does thyroid hormone have on the neuromuscular gland?
Increased synthesis of proteins associated with nueromuscular activity
What effects does thyroid hormone have on GI and repro system?
Needed for normal GI motility and reproduction
What are some clinical signs of hyperthyroidism/
Weight loss in spite of ravenous appetite, hyperactivity, PU/PD, diarrhea, vomiting, tachycardia, and hair loss
What are some clinical signs of hypothyroidism?
Lethargy, weakness, coma, obesity, cold intolerance, skin lesions, infertility, number 2 underlying cause of demodicosis
Why is T4 preferred over T3 for treatment of hypothyroidism?
T4 has a longer half life and giving T4 as replacement therapy will get plenty of T3 generated in the brain anyway
How does 131-I work as an antithyroid agent in hyperthyroidism?
It is a beta-R antagonist everywhere, especially the thyroid
This is used for non-surgical thyroidectomy
Which group of antithyroid drugs is preferred in the control of hyperthyroidism?
Methimazole
What is Methimazole’s method of action
Blocks iodide transport
What are some adverse effects of Methimazole?
Anorexia, vomiting, lethargy, eosinophilia, severe scratching, and hepatopathy
Cetecholamines devastate hyperthyroid myocardium. What drug can be used to counteract this?
Beta-blockers: Propanolol and atenalol
