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Endocrine Pharm > Thyroid Drugs > Flashcards

Thyroid Drugs Flashcards

1
Q

How does thyroid hormone initiate its actions?

A

They bind to nuclear receptors and change gene expression. This is weird b/c it is a peptide hormone.

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2
Q

What are the actions of thyroid hormone?

A
  1. Growth and development (esp. brain, bones, teeth)
  2. Calorigenic (hyper = thin/cachectic, Hypo = obese, increased O2 consumption)
  3. CV (increased beta 1 receptors in the heart)
  4. Increased metabolism
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3
Q 
What effect does thyroid hormone have on...
Fatty acids?
Bile acids?
Glycolysis?
Gluconeogenesis?
Cholesterol levels?
A 
Increase fatty acid synthesis and oxidation
increased bile acid synthesis
increased glycolysis
Increased gluconeogenesis
Decreased cholesterol levels
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4
Q

What effects does TSH have on the thyroid gland?

A 
TSH increases thyroid hormone synthesis and release by...
causing secretion of thyroid hormones
increasing iodide uptake 
increasing hormone synthesis
Increasing TH bound to TG.
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5
Q

What protein forms is the site of thyroid hormone synthesis and storage?

A

Thyroglobulin

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6
Q

What enzyme catalyzes the formation of thyroid hormone by iodinating tyrosine residues on thyroglobulin?

A

Thyroid peroxidase.

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7
Q

How is T3 usually formed?

A

By the removal of the 5’ iodine from T4 by thyronine 5’-deiodinase

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8
Q

Where is Thyroglobulin iodinated?

A

It is iodinated in the apical membrane of the follicular cell as it is secreted into the colloid space. Thyroid peroxidase is a transmembrane protein.

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9
Q

Does the thyroid gland preferentially make T3 or T4?

A

4x more T4 is made than T3. Unless there is an iodine deficiency then there is a higher proportion of T3

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10
Q

Is more T3 or T4 released into the blood stream?

A

There is 10x more T4 released into the blood stream.

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11
Q

How is T4 converted into the more active T3?

A

The peripheral tissues express thyronine 5’-deiodinase which converts T4 to T3.

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12
Q

Explain the two isoforms of thyronine 5’-deiodinase?

A

D1 = liver, kidney, and pancreas. It is primarily used for T3 that will be exported from the tissue.

D2 = brain, pituitary, heart, skeletal muscle, used to maintain intracellular T3

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13
Q

What is reverse T3?

A

Thyronine 5-iodinase makes rT3 which is an inactive variant of T3

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14
Q

What happen if a pregnant mother develops hypothyroidism?

A

The baby may develop cretinism. This is b/c the developing fetus needs thyroid hormone for proper CNS development. The mother is the fetus’s only source of TH.

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15
Q

How is Thyroid hormone metabolized and excreted?

A

TH is metabolized in the liver by glucuronidation and sulfate conjugation.
TH is excreted in the bile and undergoes enterohepatic recirculation thanks to the resident microbiota.

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16
Q

Explain the protein binding properties of thyroid hormone?

A

1.Mostly bound to thyroid binding globulin (TBG)
T4 binds better than T3
2. Transthyretin binds T4 better and is the main transport in the CSF
3. Albumin binds both T3 and T4 equally.

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17
Q

Is more TH bound by protein or free? Which version is physiologically active?

A

Most TH is protein bound

Only the free hormone is physiologically active.

18
Q

What stimulates the release of thyroid hormone?

A

TSH

19
Q

What factors decrease the release of TSH?

A
  1. Somatostatin
  2. Dopa
  3. Drugs
  4. Glucocorticoids
20
Q

What factors increase the release of TSH?

A

Catecholamines

21
Q

What happens to thyoid hormones when iodine levels are extremely high?

A

Extremely high iodine levels suppress the production and secretion of thyroid hormones.

22
Q

What happens in Iodine deficiency?

A
  1. decreased thyroid hormone production
  2. oversecretion of TSH
  3. Thyroid hyperplasia (Goiter)
23
Q

What are the long term effects of iodine deficiency?

A

Hypothyroidism/cretinism in adults

retardation in kids (mcc worldwide)

24
Q

What is the treatment for Iodine deficiency?

A

Iodized salt

25
Q

What are some causes of hypothyroidism?

A
  1. AI disease
  2. Congenital disease
  3. Radiation
  4. Drug induced
26
Q

What is the treatment for hypothyroidism?

A

Replace the hormone

27
Q

What are different thyroid hormone preps that are available?

A
  1. Levothyroxine
  2. Liothyronine sodium
  3. Liotrix
  4. Dessicated animall thyroid preps
28
Q

What is unique about levothyroxine?

A

T4 that can take weeks to reach a steady state level. T3 and T4 levels must be monitored closely.

29
Q

What is unique about Liothyronine sodium?

A

T3 that is available in tablet or injectable form

30
Q

What is unique about Liotrix?

A

Liotrix is a mixture of T3 and T4.

31
Q

What is unique about dessicated animal preps?

A

They do not work very well because their composition can be highly variable.

32
Q

What are some causes of hyperthyroidism?

A
  1. Graves disease

2. tumor (rare)

33
Q

What are the treatments for Hyperthyroidism?

A
  1. Surgery
  2. Radioactive iodine
  3. drugs
34
Q

What drugs are used to treat hyperthyroidism?

A

The thioureylenes

  1. Propylthiouracil
  2. methimazole
  3. Carbimazole
35
Q

What is the MOA of Propylthiouracil?

A

PTU inhibits thyronine 5’-deiodinase as well as thyroid peroxidase

36
Q

What adverse effects are associated with propylthiouracil?

A

Rash

agranulocytosis

37
Q

Which drug used for hyperthyroidism is more potent? Which has a longer half life?

A

Methimazole is both more potent and has a longer half life than PTU

38
Q

What is the preferred treatment for hyperthyroidism in a pregnant woman?

A

Propylthiouracil b/c it doesn’t cross the placenta or get concentrated in breast milk.

39
Q

What is a potential concern when using iodinated contrast media?

A
  1. Incident hyperthyoidism in euthyroid patients

2. thyroid storm in hypertrophied patients

40
Q

What is the treatment for thyroid storm?

A

Give very large dose of Iodine. This will stun the thyroid. This is also useful in preoperative gland shrinkage.

41
Q

What is the therapeutic utility of radioactive iodine?

A

radioactive I131 is concentrated in the thyroid, thus delivering focused radiation to the gland and killing it. It doesn’t affect other tissues, although it is contraindicated in pregnancy b/c it will destroy the fetus’s thyroid.

Endocrine Pharm (7 decks)

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