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Pharm > Lecture 29: Thyroid Gland Pharmacology > Flashcards

Lecture 29: Thyroid Gland Pharmacology Flashcards

1
Q

What classes does the thyroid gland release?

A
  • T3 (triiodothyronine) and T4 (thyroxine) thyroid hormones

* Calcitonin

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2
Q

What is the most active thyroid hormone?

A

T3 (triiodothyronine)

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3
Q

What causes the release of TSH from the anterior pituitary?

A

The release of TRH from the hypothalamus

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4
Q

What is TRH and what does it do?

A

A hormone released from the hypothalamus that stimulates TSH to be released from the anterior pituitary

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5
Q

What does TSH do?

A

It is released from the anterior pituitary and causes the release of T4 and T3 from the thyroid

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6
Q

What inhibits the release of TRH from the hypothalamus?

A

T4 and T3 from the thyroid

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7
Q

What inhibits the release of TSH from the anterior pituitary?

A

T4 and T3 from the thyroid

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8
Q

What are the physiological effects of T4 and T3?

A
  • Increased basal metabolic rate
  • Sensitization to catecholamine (increased cardiac output, heart rate, breathing rate)
  • Important role in growth and development
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9
Q

What are Thyroid hormones made up of?

A

Two modified tyrosine molecules

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10
Q

What is the precursor protein to Thyroid hormone and what is it rich in?

A

Thyroglobulin and it is tyrosine rich

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11
Q

What happens to the tyrosines to make thyroid hormones?

A
  • They are enzymatically iodinated

* The iodinated tyrosines are enzymatically coupled

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12
Q

What does TSH stimulation do?

A

Causes the thyroid hormone precursor protein to be endocytosed and processed. And then T4 and T3 can be released

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13
Q

Where does Iodination and coupling of thyroglobulin happen?

A

On the Apical side (follicle lumen)

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14
Q

Where is Thyroglobulin processed after it has been iodinated and coupled?

A

Within the cell (so not the lumen of the follicle)

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15
Q

Where are T4 and T3 released from after being generated from thyroglobulin?

A

The basolateral side of the cell, so to the bloodstream

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16
Q

What are thyroid follicles?

A

Rings made up of multiple cells that form around a lumen

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17
Q

What do the thyroid cells release into the follicle?

A

Thyroglobulin

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18
Q

What does Thyroperoxidase do?

A

It iodinates and couples Thyroid hormone

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19
Q

What happens if the thyroid is inactive?

A

The lumen of the gland will fill with colloid

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20
Q

What is Colloid?

A

Fluid that is rich in unprocessed thyroglobulin that is waiting for the signal to be processed

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21
Q

What does TSH trigger?

A

Exocytosis of thyroglobulin so it can be processed into T3 and T4

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22
Q

How does the the Thyroid gland get iodine?

A

It concentrates iodine from the bloodstream using the Na+/I- cotransporter

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23
Q

Where is Iodide transported?

A

To the follicle lumen and eventually added to thyroglobulin

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24
Q

What kind of receptor is the thyroid hormone receptor?

A

An intracellular type receptor

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25
Q

What does the thyroid hormone receptor do after binding of thyroid hormone?

A

Acts as a transcription factor after binding of thyroid hormone

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26
Q

What do T3 and T4 need to do in order to bind the Thyroid hormone receptor?

A

They need to be taken up into cells by a transporter protein (instead of just diffusing through the membrane) in order to access the receptor

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27
Q

Where is the receptor for T3 or T4 located?

A

In the nucleus already bound to transcription factors

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28
Q

What happens with at rest/unbound thyroid hormone receptors?

A

They associate with response elements and recruit co repressors which weakens gene transcription

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29
Q

What happens if T4 is taken up into a cell?

A

T4 is typically de-iodinated to form T3

30
Q

What does T3 binding in the nucleus cause?

A

It causes recruitment of RAR (retinoic acid receptor) to form a heterodimer with the thyroid hormone receptor

31
Q

What does the recruitment of coactivators when T3 is bound do?

A

Leads to enhanced transcription of gene

32
Q

How fast is T3 and T4 activation of receptors?

A

It is slow

33
Q

What is Hypothyroidism?

A

Deficient thyroid function (not enough release of thyroid hormone)

34
Q

What are the most common causes of Hypothyroidism?

A
  • Iodine deficiency (dietary)
  • Autoimmunity towards thyroid (Hashimoto’s thyroiditis)
  • Congenital defect
  • Inappropriate hormonal regulation (insufficient TSH or TRH)
35
Q

What are the symptoms of Hypothyroidism?

A
  • Fatigue
  • Weight gain
  • Hypersensitivity to cold
  • Bradycardia
36
Q

What are the two types of Hypothyroidism?

A

Primary and Secondary hypothyroidism

37
Q

What causes primary hypothyroidism?

A

Defect in thyroid function

38
Q

What are the features of Hypothyroidism? (hormone levels)

A

Low T4 and T3 but high TSH

39
Q

What is the cause of Secondary Hypothyroidism?

A

•Central defect (poor function of anterior pituitary or hypothalamus)

40
Q

What are the feature of secondary hypothyroidism?

A
  • Low T4 and T3

* Low TSH

41
Q

Why does secondary hypothyroidism have low Low TSH and the other one has high TSH?

A

Because in primary hypothyroidism the gland is not producing enough T4 and T3 so there is no negative feedback inhibiting TSH. In Secondary hypothyroidism, the CNS us unable to release TSH

42
Q

What is the treatment for Hypothyroidism?

A

Hormone replacement with Synthetic thyroxine (levothyroxine)

43
Q

What is Hyperthyroidism?

A

Overactive Thyroid function (excessive production of thyroid hormone)

44
Q

What are the most common causes of Hyperthyroidism?

A
  • Graves disease

* Hyperplasia of the thyroid

45
Q

What is Graves disease?

A

When stimulatory antibodies are released against the TSH receptor and activates them leading the excess thyroid hormone release

46
Q

What are the symptoms of Hyperthyroidism?

A
  • Sleep difficulty
  • Heat (temperature) intolerance
  • Tachycardia
  • Weight loss
  • Tremor
47
Q

What is Graves disease caused by?

A

Stimulation of thyroid by anti-TSH receptor antibodies

48
Q

What are the features of graves disease? (Hormones)

A
  • High T4 and T3
  • Low TSH
  • Detection of anti-TSH antibodies
  • Bulging eyes
49
Q

What is Thyroid hyperplasia caused by?

A

Thyroid adenoma, goiter

50
Q

What are the features of Thyroid Hyperplasia? (hormones)

A
  • High T4 and T3

* Low TSH

51
Q

What is the cause of Secondary Hyperthyroidism?

A

Central defect (excessive production of TSH by anterior pituitary)

52
Q

What are the features of Secondary Hyperthyroidism? (hormones)

A

High T4 and T3 and high TSH

53
Q

What are the two Thyroid Autoimmune diseases?

A

Graves disease and Hashimoto’s disease

54
Q

What happens in graves disease?

A

The antibodies cause stimulation of the TSH receptor

55
Q

What happens in Hashimoto’s thyroiditis?

A

Antibodies recognize other thyroid-specific proteins and lead to damage of the thyroid

56
Q

What happens to the cells around the follicle when they become active?

A

The cells around become larger and the lumen becomes smaller

57
Q

What happens to the follicle in graves disease?

A

Hyperstimulation of the follicles and so they look like an active state where the cells are big and the lumen will shrink and all the colloid is used up and spit out as thyroid hormone

58
Q

What happens to the follicles in Hashimoto’s thyroiditis?

A

Lymphocytes infiltrate the thyroid gland that attack the thyroid follicle and cause it to die

59
Q

What are some of the physical features of Hyperthyroidism?

A
  • Exophthalmos (bulging eyes)

* Goiter (swelling in the neck)

60
Q

What are the four treatments of Hyperthyroidism?

A
  • Surgery
  • Radioactive iodine treatment
  • Antithyroid drugs
  • Symptomatic treatment with beta-blockers
61
Q

What is the drawback to using surgery to treat hyperthyroidism?

A
  • It can disrupt the parathyroid glands causing disturbances in Ca2+
  • It needs management for hypothyroidism
62
Q

What is the approach for radioactive iodine treatment for Hyperthyroidism?

A

Iodine is concentrated within the thyroid and radiation leads to the destruction of the thyroid

63
Q

What are the drawbacks to radioactive iodine treatment?

A

It should not be used during pregnancy

64
Q

What is the approach to anti-thyroid drugs to treat hyperthyroidism?

A

They prevent several steps in T4/T3 synthesis

65
Q

What are the drawback to anti-thyroid drugs?

A

They have diverse side effects

66
Q

What is the approach to Symptomatic treatment of hyperthyroidism with Beta-blockers?

A

They may help with issues such as tachycardia

67
Q

What is the drawback to treatment of hyperthyroidism with betablockers?

A

It does not influence the underlying cause of the disease

68
Q

What is a drug to treat hyperthyroidism?

A

Thioamides (Methimazole)

69
Q

What is Methimazole used to treat?

A

Hyperthyroidism

70
Q

How does Methimazole work?

A

It prevents the iodination and coupling steps mediated by Thyroperoxidase

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