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Flashcards in Thyroid Drugs Deck (49)
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1

major steps in thyroid hormone synthesis

  1. Uptake of iodide ion (I–) by the thyroid gland.
  2. Oxidation of iodide to iodine.
  3. Iodination of tyrosyl groups of thyroglobulin.
  4. Coupling of iodotyrosine residues to generate the thyroid hormones.
  5. Resorption of the thyroglobulin colloid from the lumen into the cell.
  6. Proteolysis of thyroglobulin and the release of thyroxine and triiodothyronine into the blood.

2

T_ acts more rapidly and is more potent than T_
because it is __ tightly bound to plasma proteins and binds more avidly to TH receptors

T3 acts more rapidly and is more potent than T4 

because T3 is less tightly bound to plasma proteins and binds more avidly to TH receptors

3

physiological effects of thyroid hormone 

4

mechanisms thyroid hormone is metabolized

  • Deiodination (most important)
  • Glucuronidation
  • Sulfation

5

Deiodination of T4 by ____ results in the production of either T3 (more potent than T4) or reverse T3 (metabolically inactive)

Deiodination of T4 by 5′deiodinase results in the production of either T3 (more potent than T4) or reverse T3 (metabolically inactive)

6

5′deiodinase inhibited by:

1. Drugs such as (4)

2. Severe illness and starvation

3. Iodinated compounds such as the radiographic agents iopanoic acid and ipodate

5′deiodinase inhibited by:

1. Drugs: propylthiouracil, propranolol, corticosteroids, amiodarone

2. Severe illness and starvation

3. Iodinated compounds such as the radiographic agents iopanoic acid and ipodate

7

T4 and T3 are also conjugated in the ___ to form sulfates and glucuronides

These conjugates enter the __ and pass into the intestine where they are hydrolyzed

some are ___ (enterohepatic circulation), others are excreted in stool

T4 and T3 are also conjugated in the liver to form sulfates and glucuronide

These conjugates enter the bile and pass into the intestine where they are hydrolyzed

some are reabsorbed (enterohepatic circulation), others are excreted in stool

8

In the intestine, ____ (e.g. __) bind to and prevent the enterohepatic cycling of thyroid hormones

In the intestine, Bile acid sequestrants (e.g. cholestyramine) bind to and prevent the enterohepatic cycling of thyroid hormones

9

Deiodinase and UDP-glucuronosyltransferase enzymes are inducible, ___ the metabolism of T3 and T4

Enzyme inducer: ___

Clinical use for this? 

 

Deiodinase and UDP-glucuronosyltransferase enzymes are inducible, increasing the metabolism of T3 and T4

Enzyme inducer: rifampin

Patients dependent on T4 replacement medication may require increased dosages to maintain clinical effectiveness if they are also on an enzyme inducer

10

clinical manifestations of hypothyroidism

  • goiter
  • muscle weakness, lethary
  • dry coarse skin and hair
  • yellowish tint of the skin
  • cold intolerance, cold skin
  • decreased sweating
  • thick tongue
  • delayed DTRs

11

___ is the most common cause of hypothyroidism in the USA

___ is the most common cause worldwide

 

Hashimoto's thyroiditis the most common cause of hypothyroidism in the USA

Iodine deficiency is the most common cause worldwide

12

list other causes of hypothyroidism

  • thyroidectomy
  • external neck irradiation
  • RAI therapy
  • drug-induced

13

Drugs that can cause hypothyroidism

  • Thioamides
  • Iodides
  • Amiodarone
  • Lithium
  • Aminoglutethimide
  • Rifampin
  • TKI's (e.g., imatinib, sunitinib, sorafenib)
  • Interleukin 2
  • Interferon-α
  • Sulfonylureas

14

treating amioderone-induced hypothyroidism

Levothyroxine even after amioderone discontinuance (bc of amioderones very long half-life)

15

Levothyroxine Vs. Liothyronine

16

Synthetic _____ is the preparation of choice for thyroid hormone replacement therapy

Synthetic levothyroxine (T4) is the preparation of choice for thyroid hormone replacement therapy

17

Thyroid replacement therapy AEs

  • hyperthyroid-like manifestations
  • ↑ risk of atrial fibrillation and osteoporosis

18

____ is a severe and long-standing form of hypothyroidism

describe cardinal features

 

Myxedema coma is a severe and long-standing form of hypothyroidism:

Hypothermia
Respiratory depression
Decreased consciousness

19

Management of myxdemea coma: IV ___

 ___ may be added until the patient is stable and conscious

Management of myxdemea coma: IV levothyroxine

Liothyronine may be added until the patient is stable and conscious

20

During pregnancy, adequate dose of ___ is important as early development of the fetal ___ depends on maternal thyroxine

During pregnancy, adequate dose of levothyroxine is important as early development of the fetal brain depends on maternal thyroxine

21

A higher dose of levothyroxine is usually required in pregnant patients - why? 

 

1. ↑ [TBG] induced by estrogen

2. Expression of 5′deiodinase 3 (D3) by the placenta

3. Small amount of transplacental passage of levothyroxine from mother to fetus

22

Congenital hypothyroidism treatment depends on the __ and ___ with which hypothyroidism is corrected 

If ____ is instituted within ___, normal physical and mental development can be achieved

Congenital hypothyroidism treatment depends on the age and speed with which hypothyroidism is corrected 

If levothyroxine is instituted within first 2 weeks of life, normal physical and mental development can be achieved

23

Clinial features of hyperthyroidism

  • nervousness, heat intolerance
  • increased sweating, palpitations
  • fatigue, weakness, dyspnea
  • weight loss with increased appetite
  • signs: goiter with bruit over thyroid, tachycardia, skin changes and eye signs

24

____ is most common cause of hyperthyroidism

Other causes?

Grave’s disease (toxic diffuse goiter) is most common cause of hyperthyroidism

  • toxic adenoma
  • toxic multinodular goiter
  • factitious hyperthyroidism
  • Drug-induced

25

Drug-induced hyperthyroidism 

  • Iodides
  • Amiodarone
  • Interleukin 2
  • Interferon-α
  • Lithium

26

Drugs used in the management of hyperthyroidism

  • Thioamides
  • Iodides
  • β-antagonists
  • Glucocorticoids
  • Bile acid sequestrants

27

Thiomides

Methimazole, Propylthiouracil (PTU)

28

Methimazole, Propylthiouracil (PTU) inhibit formation of thyroid hormones by inhibiting ____ 

Methimazole, Propylthiouracil (PTU) inhibit formation of thyroid hormones by inhibiting thyroid peroxidase (oxidation, iondination, coupling) 

29

what effect does propylthiouracil have that Methimazole does not?

making PTU the preferred treatment of ____

Propylthiouracil can also inhibit conversion of T4 → T3 

making PTU the preferred treatment of severe hyperthyroid and thyroid storm

30

Thioamides clinical indications 

  • hyperthyroidism
  • PTU: DOC for thryoid storm
  • In conjunction with radioactive iodine, to hasten recovery while awaiting the effects of radiation
  • Control hyperthyroidism in preparation for surgical treatment