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Pharmacology B > Lecture 11 - Thyroid > Flashcards

Lecture 11 - Thyroid Flashcards

1
Q

Describe the thyroid hormone loop (slide 3)

A

Hypothalamus releases TRH and it goes to the anterior pituitary.
Anterior pituitary releases TSH to the thyroid.
T3 and T4 then release tissue effects.

*T4 and T3 has negative feed-back inhibiton on the anterior pituitary

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2
Q

TRH

A

thyrotropin releasing hormone

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3
Q

TSH

A

thyroid stimulating hormone

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4
Q

T4 is also known as _______

A

levothyroxine

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5
Q

T4 splits up into ??

A

T3 and rT3

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6
Q

What is the half-life of T4 (levothyroxine)?

A

7 days

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7
Q

What is the half-life of T3?

A

1 day

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8
Q

Describe the metabolism of T4 (levothyroxine)?

A

20% inactivated
80% converted to T3

(35% to T3, 45% to rT3)

  • glucuronidation and salvation in the liver
  • excretion in urine and bile
  • conjugates reconverted to T4 in lower GIT
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9
Q

T4 and T3 have a negative feedback relationship on ___

A

TSH

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10
Q

Normal range for T4?

A

64-142 nM

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11
Q

Normal range for T3?

A

1.5-2.9 nM

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12
Q

Normal range for TSH?

A

0.3-5 mU/L

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13
Q

Normal range for Serum Thyroglobulin?

A

<40 ng/mL

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14
Q

Hypothyroid range for T4?

A

low

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15
Q

Hyperthyroid range for T4?

A

high

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16
Q

Hypothyroid range for T3?

A

normal or low

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17
Q

Hyperthyroid range for T3?

A

high

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18
Q

Hypothyroid range for TSH?

A

high

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19
Q

Hyperthyroid range for TSH?

A

low

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20
Q

Hypothyroid range for Serum Thyroglobulin?

A

low

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21
Q

Hyperthyroid range for serum Thyroglobulin?

A

high

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22
Q

Children have higher ___ than adults

A

T3

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23
Q

Hypothyroidism is a ___% incidence

A

0.6

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24
Q

Hypothyroidism is more common in _____

A

women

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25
Q

______ ______ is an autoimmune disorder

A

Hashimoto’s Thyroiditis

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26
Q

Describe the presentation of hypothyroidism

A

Slowing of body functions:
-Heart, mental acuity, strength, response to catecholamines, cold and scaly skin, sparse hair, puffiness (myxadema), droopy eyelids, saddle nose thickened lips

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27
Q

What is the cause of Hashimoto’s thyroiditis?

A

Antibodies against thyroid peroxidase and/or thyroglobulin gradually destroy thyroid gland follicles

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28
Q

Symptoms of Hashimoto’s thyroiditis?

A

Slower metabolism, reduced CNS activity - weight gain, fatigue, depression, bradycardia, constipation, muscle weakness, memory loss, infertility, hair loss

**NOTE - HT can also cause reactive HYPERthyroidism (inflammation), and thus mania, tachycardia, panic attacks. Mania due to HT is called Prasad’s Syndrome

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29
Q

What is Hashimoto’s thyroiditis often misdiagnosed as ?

A

depression or anxiety, sometimes even as bipolar disorder

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30
Q

How do we detect Hashimoto’s thyroiditis?

A
  • Presence of specific antibodies is diagnostic

- Also see increased TSH and often lymphocyte invasion of thyroid gland

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31
Q

Describe the Diagnosis of Hashimoto’s Diagnosis

A
  • Enlargement of the thyroid, known as a goiter
  • High levels of antibodies against thyroglobulin (TG) and thyroid peroxidase (TPO), detected via blood test
  • Fine needle aspiration of the thyroid (also known as a needle biopsy), which shows lymphocytes and macrophages
  • A radioactive uptake scene, which would show diffuse uptake in an enlarged thyroid gland
  • Ultrasound, which would show an enlarged thyroid gland
32
Q

What do thyroid hormones do?

A

Increase adrenergic receptor sensitivity to catecholamines:

-Normal adrenalin/Noradrenalin, hyper response

33
Q

Do thyroid hormones cross the placenta?

A

Not in clinically meaningful amounts

34
Q

Pregnant patients with hypothyroidism is ______

A

difficult

35
Q

Pregnant patients with hyperthyroidism causes _____

A

abortion

36
Q

If pregnant, must carefully monitor dose regiment because of _____

A

stimulation

37
Q

What is the treatment for hypothyroidism?

A

*If due to iodine deficiency, then add iodine to the diet (elderly/poverty)

  • For gland failure, levothyroxine (T4) is the treatment of choice:
  • Long half life
  • Lag before effects are observed
  • Given at birth to prevent cretinism
  • Body then converts T4 (levothyroxine) to T3 as required
38
Q

Prevalence of hyperthyroidism?

A
  • most common between 20-60 years of age

- more prevalent in females

39
Q

What is grave’s disease?

A
  • most common form of hyperthyroidism

- activating Ab to TSH receptor causes increased T3 and T4 levels

40
Q

Diagnosis of hyperthyroidism of patients less than 40?

A

mainly nervous system effects

41
Q

Diagnosis of hyperthyroidism of patients more than 40?

A

mainly CV effects

42
Q

Another diagnostic criteria for hyperthyroidism?

A

catecholamine response

43
Q

Describe Radioiodone

A

-The treatment of choice at many centres
125I half life = 60 days
131I half life = 8 days (beta particles, kills cells)
123I half life = 0.55 days (would need quick delivery)

  • Ionizing radiation destroys the gland
  • Caution with other antithyroid drugs as must be concentrated into uptake gland
  • Stop for 2 days before and after
44
Q

Radioiodine contraindications?

A

CI in pregnancy and in children

45
Q

Describe some precautions with radioiodine

A
  • Delay in therapeutic response (2-6 months)
  • Depending on symptoms, may need other pharm intervention because of delay
  • Radiation-induced thyroiditis
  • Hypothyroidism - if destroy too much
  • Thyroid cancer - discourages some patients, may choose surgery (but also damage risk … i.e. parathyroids)
  • Pregnancy!!!
46
Q

List 3 Antithyroid drugs

A
  • Propylthiouracil
  • Methimazole
  • Carbimazole
47
Q

MOA of Thioamide drugs?

A

Blocks synthesis of thyroid hormones:

  • Interferes with organification of iodine - a competitive inhibitor of peroxidase
  • Blocks MIT conversion to DIT
  • Inhibits coupling of iodinated tyrosines
  • Does not affect uptake of iodine or T4 or T4 release
  • Onset requires depletion of thyroid hormone stores
48
Q

Propylthiouracil inhibits conversion of ______?

A

T4 to T3

49
Q

Describe Thioamide Drug Disposition

A
  • Concentrated in the thyroid gland (~100 x)
  • Potency of methimazole compared to PTU is ~ 100X
  • Disposition altered in cirrhosis and in renal failure
  • Treatment: methimazole once daily and PTU every 8 hours
50
Q

Methimazole:

Half life ?

A

6 hours

51
Q

PTU:

Half life ?

A

1 hour

52
Q

Methimazole:

Protein binding ?

A

Nil

53
Q

PTU:

Protein binding ?

A

High

54
Q

Antithyroid drug therapy adjusted and/or reduced every _____ weeks

A

4-6

55
Q

Methimazole:

Maintenance dose ?

A

5-10 mg/day

56
Q

PTU:

Maintenance dose ?

A

50-100 mg/day

57
Q

PTU is used for what?

A

fast decrease in T3 due to peripheral effects - feel better faster

58
Q

In pregnancy, ____ is preferred

A

PTU

  • crosses placenta less
  • no teratogenic reports
  • only 1/10 crosses into breast milk
59
Q

SE of thioamide drugs?

A

1-5% show fever, rash, arthritis-like symptoms

  • Most common = leukopenia (WBC < 4000 mm^3)
  • Low cross reactivity between methimazole and PTU
60
Q

____ changes with thyroid status

A

WBC

*therefore, routine monitoring not recommended

61
Q

When should you stop thioamide drug therapy

A

Stop drug therapy at first sign of a sore throat and/or fever
*Then determine WBC status

62
Q

Thioamide drugs could also cause Agranulocytosis - what is that?

A

an acute condition involving a severe and dangerous leukopenia (lowered white blood cell count), most commonly of neutrophils causing a neutropenia in the circulating blood

*rare and usually reversible when drug treatment is stopped

63
Q

Describe a thyroid storm

A
  • Greatly increased blood temperature
  • Shortness of breath
  • Anxiety
  • Sweating
  • Tachycardia
  • Chest pain
  • MI
64
Q

Describe how propranolol works?

A
  • It is used to ameliorate CV symptoms/toxicity

- Some suppression of T4 to T3

65
Q

Dexamethasone:

MOA

A

inhibits T4 to T3

66
Q

Lithium:

MOA

A

inhibits secretion and degradation in peripheral tissue

67
Q

Sulfonamides:

MOA

A

interfere with organification of iodine

68
Q 
Sodium nitroprusside (long term):
MOA
A

thiocyanate accumulation inhibits iodine uptake by the thyroid

69
Q

Amiodarone:

MOA

A

contains lots of iodine

70
Q

SCN (found in some foods) and ClO4-:

MOA

A

block iodide uptake

71
Q

Iodide (large doses):

MOA

A

Decreases degranulation of thyroglobulin and gland vascularity.
It is useful prior to surgery but the effect disappears after a few days of intake.

72
Q

_________ for replacement therapy

A

Levothyroxine (T4)

73
Q

______ for hyperthyroidism except in women of child-bearing age

A

Radioiodine

74
Q

______ and ____ for hyperthyroidism

A

Methimazole and PTU

75
Q

____ is the drug of choice in pregnancy for hyperthyroidism

A

PTU

76
Q

List a few other agents with antithyroid action

A
  • amiodarone
  • lithium
  • sulfonamides

Pharmacology B (21 decks)

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