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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?

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
What are the adverse effects of thyroid replacement in the geriatric population?
A-fib and osteoporosis
26
What are the causes of Primary Hyperthyroidism?
1) Grave'e Disease 2) Thyroid adenoma/ carcinoma 3) Autoimmune thyroiditis 4) Thyroid storm 5) Excess iodide
27
What is Grave's Disease?
Autoantibodies stimulate TSH receptors to increase T3 and T4 *TSH will be LOW*
28
What is a thyroid storm?
Acute episode of excessive thyroid hormone release e.g. - Surgery - Infection - DKA ****This can be fatal b/c of the cardiovascular effects*****
29
What is the mechanism by which excess iodide causes HYPERthyroid?
* Negative regulatory processes have failed* - Idiopathic - More common with UNDERLYING thyroid disease
30
What is Secondary Hyperthyroidism?
Dysfunction of the Hypothalamis of Pituitary leading to elevated thyroid hormones
31
List the thioamides.
Methimazole | Propylthiouracil
32
What is the MOA of the thioamides?
Inhibition of all the processes that are taking place in the colloid of the thyorid follicle I.e. inhibition thyroid synthesis
33
What is the black box warning with Propylthiouracil (PTU)?
Severe hepatitis
34
What is the adverse effect assocaited with Methimazole?
Altered taste and smell
35
Which thioamide is better to use in pregnancy?
PTU
36
What thioamide is better to use for thyroid storm?
PTU b/c it is absorbed faster
37
What is the MOA of the iodides?
Increased iodine that has a negative regulatory effect on thyroid hormone synthesis
38
List the Iodides.
Potassium iodide | Lugol's Solution
39
What are the drawbacks to the Iodides?
- Will only work for 2-8 weeks | - Sudden withdrawal will cause thyrotoxiosis (burst of thyroid hormone)
40
What are the iodides a good strategy to treat?
1) Thyroid storm | 2) Preoperative prep for surgery
41
What key adverse effects are associated with Iodides?
Cold sx.
42
What is the MOA of radioactive iodine?
Emission of beta and gamma rays - Beta= induces tissue damage - Gamma= measure levels/ dose
43
What is the most common adverse effect of radioactive iodine?
Complete knockout of the thyroid gland--Hypothyroidism
44
What patient population is radioactive iodine contraindicated in?
Pregnant
45
What is the MOA of the anion inhibitors?
Inhibition of the NIS transporter
46
List the Anion Inhibitors.
Perchlorate Pertechnetate Thiocyanate
47
What is the clinical utility of the anion inhibitors?
Treatment of iodide-induced hyperthyroidism
48
What are the key antithyroid adjuncts?
1) Propanolol 2) Diltiazem 3) Barbiturates 4) Bile acid seqestrants
49
Why is propanolol a good drug for hyperthyroid?
1) Blocks sx. of hyperthyroid | 2) Prevents conversion of T4 to T3
50
What is the utility of Diltiazem in Hyperthyroid?
Good alternative to propanolol in a patient with asthma

Pharmacology (64 decks)

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