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Pharmacology > EXAM #5: THYROID AND ANTITHYROID DRUGS > Flashcards

EXAM #5: THYROID AND ANTITHYROID DRUGS Flashcards

1
Q

What is the difference between T3 and T4?

A 
T3= active 
T4= pro-hormone
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2
Q

What are four general functions of the thyroid hormones?

A

1) Growth
2) Development
3) Body temperature
4) Energy metabolism

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3
Q

Outline the steps of thyroid hormone synthesis.

A

1) Iodide uptake
2) Oxidation of Iodide to Iodine
3) “Iodide Organification” i.e. iodination of tyrosine residues on the thyroglobulin molecule
- MIT
- DIT
4) “Coupling” - MIT and DIT are combined to make T3 and T4

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4
Q

What is responsible for Iodide uptake into the thyroid gland?

A

Sodium-Iodide Symporter (NIS)

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5
Q

How are the thyroid hormones secreted?

A

1) Thyroglobulin is taken up by thyroid cell
2) Degradation of Thyrogobulin releases T3 and T4
- 5:1 ratio of T4:T3
3) Majority is bound to thyroxine-binding globulin in the blood

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6
Q

Describe the MOA of the thyroid hormone.

A

Absence of hormone:

  • T3 receptor (TR) has a ligand binding domain and a DNA binding domain
  • Dimer of TR is bound to TRE and represses transcription

Hormone:

  • Ligand binding causes dissociation of TR from TRE
  • Transcription ensues
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7
Q

What converts T4 into active T3?

A

5’-deiodinase

Note that this is a drug target

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8
Q

Outline the regulation of thyroid hormone release (HPA axis).

A

1) Hypothalamus= TRH
2) Anterior Pituitary= TRH promotes release of TSH
3) Thyroid= TSH promotes synthesis of T3 and T4

Thyroid hormone feedsback on Hypothalamus and Anterior Pituitary

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9
Q

How does iodine regulate thyroid hormone synthesis?

A
  • High blood iodine= inhibit thyroid hormone synthesis

- Low blood iodine= promotes thyroid hormone synthesis

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10
Q

What are the effects of thyroid hormone on the SNS?

A

1) Increased B-adrenergic receptors

2) Decreased a-adrenergic receptors

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11
Q

What is the effect of thyroid hormone on the respiratory system?

A

Increased O2 consumption and respiratory rate

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12
Q

What is the effect of thyroid hormone on the GI system?

A

Increased secretions and motility

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13
Q

What is the effect of thyroid hormone on glycosaminoglycans?

A

Prevents accumulation of glycosaminoglycans in the interstitial space

These result in edema and puffy/baggy eyes in HYPOTHYROIDISM

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14
Q

What is the effect of thyroid hormone on LDL receptor expression and cholesterol?

A

Thyroid hormone:

1) Decreases circulation of cholesterol
2) Increases LDL expression

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15
Q

What is myxedema?

A

Puffy/baggy eyes in HYPOTHYROIDISM

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16
Q

What are the causes of Type I/ Primary Hypothyroidism?

A

1) Congenital defect–Cretinism
2) Autoimmune Thyroiditis–Hashimoto’s Disease
3) Iodide Deficiency
4) Other
- Surgery
- Radiation
- Medications e.g. Lithium

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17
Q

What causes Type II or Secondary Hypothyroidism?

A

Impaired TSH production:

  • Head trauma
  • Cranial neoplasm

…etc.

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18
Q

What drugs are used to treat Hypothyroid?

A

Levothyroxine
Liothyronine
Liotrix

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19
Q

What is Levothyroxine?

A

T4

*Most common b/c it is more stable and cheaper

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20
Q

What is Liothyroine?

A

T3

*More potent with short half-life

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21
Q

What is Liotrix?

A

T3 and T4

22
Q

What do you need to remember about Hypothyroidism and the geriatric population?

A

Hypothyorid is PROTECTIVE; treating it can be detrimental

23
Q

What are the adverse effects of thyroid replacement in children?

A
  • Restlessness
  • Insomnia
  • Accelerated bone maturation
24
Q

What are the adverse effects of thyroid replacement in adults?

A
  • Nervousness
  • Heat intolerance
  • Palpitations
  • Tachycardia
  • Weight loss
25
Q

What are the adverse effects of thyroid replacement in the geriatric population?

A

A-fib and osteoporosis

26
Q

What are the causes of Primary Hyperthyroidism?

A

1) Grave’e Disease
2) Thyroid adenoma/ carcinoma
3) Autoimmune thyroiditis
4) Thyroid storm
5) Excess iodide

27
Q

What is Grave’s Disease?

A

Autoantibodies stimulate TSH receptors to increase T3 and T4

TSH will be LOW

28
Q

What is a thyroid storm?

A

Acute episode of excessive thyroid hormone release e.g.

  • Surgery
  • Infection
  • DKA

This can be fatal b/c of the cardiovascular effects*

29
Q

What is the mechanism by which excess iodide causes HYPERthyroid?

A
  • Negative regulatory processes have failed*
  • Idiopathic
  • More common with UNDERLYING thyroid disease
30
Q

What is Secondary Hyperthyroidism?

A

Dysfunction of the Hypothalamis of Pituitary leading to elevated thyroid hormones

31
Q

List the thioamides.

A

Methimazole

Propylthiouracil

32
Q

What is the MOA of the thioamides?

A

Inhibition of all the processes that are taking place in the colloid of the thyorid follicle

I.e. inhibition thyroid synthesis

33
Q

What is the black box warning with Propylthiouracil (PTU)?

A

Severe hepatitis

34
Q

What is the adverse effect assocaited with Methimazole?

A

Altered taste and smell

35
Q

Which thioamide is better to use in pregnancy?

A

PTU

36
Q

What thioamide is better to use for thyroid storm?

A

PTU b/c it is absorbed faster

37
Q

What is the MOA of the iodides?

A

Increased iodine that has a negative regulatory effect on thyroid hormone synthesis

38
Q

List the Iodides.

A

Potassium iodide

Lugol’s Solution

39
Q

What are the drawbacks to the Iodides?

A
  • Will only work for 2-8 weeks

- Sudden withdrawal will cause thyrotoxiosis (burst of thyroid hormone)

40
Q

What are the iodides a good strategy to treat?

A

1) Thyroid storm

2) Preoperative prep for surgery

41
Q

What key adverse effects are associated with Iodides?

A

Cold sx.

42
Q

What is the MOA of radioactive iodine?

A

Emission of beta and gamma rays

  • Beta= induces tissue damage
  • Gamma= measure levels/ dose
43
Q

What is the most common adverse effect of radioactive iodine?

A

Complete knockout of the thyroid gland–Hypothyroidism

44
Q

What patient population is radioactive iodine contraindicated in?

A

Pregnant

45
Q

What is the MOA of the anion inhibitors?

A

Inhibition of the NIS transporter

46
Q

List the Anion Inhibitors.

A

Perchlorate
Pertechnetate
Thiocyanate

47
Q

What is the clinical utility of the anion inhibitors?

A

Treatment of iodide-induced hyperthyroidism

48
Q

What are the key antithyroid adjuncts?

A

1) Propanolol
2) Diltiazem
3) Barbiturates
4) Bile acid seqestrants

49
Q

Why is propanolol a good drug for hyperthyroid?

A

1) Blocks sx. of hyperthyroid

2) Prevents conversion of T4 to T3

50
Q

What is the utility of Diltiazem in Hyperthyroid?

A

Good alternative to propanolol in a patient with asthma

Pharmacology (64 decks)

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