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Pharmacology > Thyroid & Antithyroid drugs > Flashcards

Thyroid & Antithyroid drugs Flashcards

1
Q

How is iodine synthesized into thyroid hormones?

A

iodine is covalently bound to tyrosine residues in the thyroglobulin molecules via thyroperoxidase.

MIT + DIT = triiodothyronine (T3)
DIT + DIT = thyroxine (T4)

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2
Q

what is reversible triiodothyronine (rT3)?

A
  • isomer of T3.
  • derived from T4 through deiodinase.
  • blocks action of T3.
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3
Q

what are the synthesis and secretion steps of thyroid hormones?

A
  1. uptake of iodine
  2. synthesis of thyroglobulin from A.A
  3. iodination
  4. condensation
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4
Q

What are the physiological effects of thyroxine?

A
  1. increase BMR via Na/K ATPase
    - increase RR
    - increase temperature
    - increase O2
  2. potentiates the effects of catecholamines
    - increase CO
    - enhances HR
  3. promotes CNS development.
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5
Q

PK of thyroid T3 and T4?

A
  • T3 formed from deiodination (5’-deiodinase) of T4 in the peripheral tissues, liver, kidney.
  • Thyroxin-binding protein transport T3 and T4
  • T3 has greater affinity than T4
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6
Q

Physiological controls of thyroid gland?

A
  • the pituitary gland is regulated by hypothalamus (TRH)
  • – activated by cold, acute psychosis, circadian and pulsatile rhythm.
  • – inhibited by severe stress.
  • thyroid gland is under control of the pituitary gland (TSH)
  • negative feedback is from T3 and T4.
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7
Q

MOA of thyroid hormones?

A
  • signaling mechanism is via TRH-IP3 mediated, TSH-cAMP mediated, T3 & T4 binds with receptor in the nucleus.
  • mechanism: binds c intracellular receptors that control gene expression c RNA formation and protein synthesis.
  • proteins synthesized depends on tissues involved
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8
Q

What are some thyroid preps?

A

Levothyroxine (T4) - longer t1/2

Liothyronine (T3) - short t1/2

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9
Q

Levothyroxine
Liothyronine

uses?

A 
cretinism (thyroid hormone syn defect)
adult hypothyroidism (myxedema)
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10
Q

Levothyroxine
Liothyronine

A.E?

A

tremors
tachycardia
arrythmias
heat intolerance

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11
Q

what are some P450 inductions that can increase the metabolism of T3 and T4?

A

rifampin
phenobarbital
phenytoin

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12
Q

primary hypothyroidism?

A 
Hashimoto's thyroiditis - anti-TPO
radiation exposure 
"I" deficiency
excision
drugs - lithium, amiodarone
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13
Q

secondary hypothyroidism?

A

pituitary pathology.

  • radiation, surgery or tumor
  • decrease TSH
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14
Q

Tertiary hypothyroidism?

A

hypothalamus pathology.

decreased TRH

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15
Q

hypothyroidism lab diagnosis?

A

elevated TSH
decreased total T4
decreased free T4
decreased T3

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16
Q

clinical fts of hypothyroidism?

A 
cold tolerance
constipation
poor memory
hair loss - queen anne's sign (thinning of hair lateral third of eye brow)
carpal tunnel syndrome
hoarse voice
puffy face
bradycardia
delayed DTRs
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17
Q

describe cretinism…

A

fts: mentally retarded, short stature child c protruding umbilicus, pot belly, pale& puffy face and tongue is protruding
causes: lack of dietary iodine; defect in T4 syn or devel failure of thyroid

screen and tx pts, including congenital defect, c T4 (c/in -2 wks of life)

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18
Q

hyperthyroidism lab diagnosis?

A

decreased TSH
elevated T4
elevated free T4
elevated T3

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19
Q

hyperthyroidism causes?

A 
Graves' disease
toxic multinodular goiter
toxic adenoma
molar pregnancy
postpartum thyrotoxicosis
postviral thyroiditis
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20
Q

PE/History of Hyperthyroidism?

A 
weight loss
heat tolerance
nervousness
palpitation
bowel frequency
insomnia
abnl menses
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21
Q

what are fts of Graves?

A

ophthalmopathy

pertibial myxedema

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22
Q

what are two thioamides to treat hyperthyroidism?

A

propythiouracil

methimazole

23
Q

what are two iodine & iodide salts to treat hyperthyroidism?

A

lugol sln

potassium iodide

24
Q

what is a beta blocker used in hyperthyroidism?

A

propanolol

25
Q

propythiouracil
methimazole

MOA?

A

block iodination of thyroglobulin
inhibit coupling rxn of DIT c MIT & DIT
inhibit thyroperoxidase

26
Q

Which thioamides is preferred in thyroid storm and why?

A

propythiouracil d/t its inhibitory effect on 5-deiodinase that result in decrease peripheral conversion from T4 and T3.

27
Q

what are the two uses for propythiouracil?

A
  1. reserved for pts who are intolerant to methimazole

2. preferred in thyroid storm.

28
Q

propythiouracil
methimazole

A.E?

A

propythiouracil:
rash, arthralgia
rare - agranulocytosis, aplastic anemia, hepatotoxicity, vasculitis

methimazole:
less A.E
possible teratogenic.

29
Q

What is the Wolff-Chaikoff effect?

A

give large doses of iodide inhibit thyroid synthesis.

30
Q

What is the Jod-Basedow phenomenon?

A

multinodular goiter devel after Wolff-Chaikoff effect is lost after 10-14 days.

31
Q

lugol sln
potassium iodide

actions?

A

decrease vascularity and size of the thyroid gland.

32
Q

lugol sln
potassium iodide

uses?

A

before surgery for easy thyroid excision.

conjunction c PTU, and beta blockers in thyrotoxic crisis

33
Q

lugol sln
potassium iodide

preparations?

A

Lugol: a mixture of iodine and postassium iodide.

KI: saturated sln.

34
Q

lugol sln
potassium iodide

A.E?

A

chronic iodide intoxication (iodism)
anaphylactoid rxn
- angioedema, swelling of larynx, eyelids
brassy taste
burning of teeth and gums
enlargement of parotid and maxillary glands

35
Q

Radioactive iodine 131(I)

MOA?

A

taken up and sequestered by thyroid gland -> damage the tissue through emission of toxic beta rays, no effect on other tissues.

36
Q

Radioactive iodine 131(I)

uses?

A

hyperthyroidism
Graves’ disease

refractory to other antithyroid drugs and persistent sx’s even after a subtotal thyroidectomy

37
Q

Radioactive iodine 131(I)

A.E?

A

hypothyroidism

38
Q

Radioactive iodine 131(I)

contraindications?

A

pregnant women and nursing mothers.

39
Q

propanolol

MOA?

A

prevents conversion of T4 and T3

40
Q

nadolol or atenolol

uses?

A

control tachycardias, htn, a fib during thyroid storm

41
Q

esmolol use?

A

control intra-operative thyroid storm

42
Q

diltiazem use?

A

Ca channel blocker - use in thyroid storm for pts c asthma

43
Q

what is thyroid storm?

A

assoc c extreme effects of hyperthyroidism

- caused by illness, surgery, and other stresses

44
Q

what are the two iodinated radiocontrast media?

A

diatrizoate

iohexol

45
Q

diatrizoate
iohexol

MOA?

A

suppress conversion of T4 and T3 in peripheral tissues, kidney, and liver.

46
Q

diatrizoate
iohexol

uses?

A

rapidly reduce T3 conc in thyrotoxicosis

47
Q

Perchlorate
thiocyanate
pertechnetate

MOA?

A

inhibit iodide conc in the gland by blocking transportation

48
Q

Perchlorate
thiocyanate
pertechnetate

A.E?

A

aplastic anemia

49
Q

what are drugs that can induce hypothyroidism?

A

amiodarone
interferon alpha & IL-2
lithium

50
Q

amiodarone

fts?

A

structurally similar to thyroxine

51
Q

amiodarone

A.E and tx?

A

iodine assoc hyperthyroidism - tx c thiamides
autoimmune mediated infl - tx c steroids
hypothyroidism - tx c levothyroxine

52
Q

Lithium

MOA?

A

inhibits release of hormones (hypothyroidism) and thyroid enlargement.

53
Q

what are the two goitrogens?

A

cabbage

cassava

54
Q

what is the function of the thyroid gland?

A
  • take up iodine and convert it into thyroid hormones.

Pharmacology (13 decks)

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