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ABBEY MSII Unit 5 > Pharm: thyroid and antithyroid drugs > Flashcards

Pharm: thyroid and antithyroid drugs Flashcards

1
Q

what is the precursor for thyroid hormone

A

tyrosine

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2
Q

T4

A

thyroxine

prohormone

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3
Q

T3

A

3,5,3 triiodothyronine

active hormone

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4
Q

reverse T3

A

3,3,5 triiodothyronine

inactive***

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5
Q

how is T4 converted to T3

A

type 1 (D1) and type 2 (D2) deiodinases

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6
Q

D1 expressed where

A

liver and kidney

~24% T4-T3 conversion

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7
Q

D2 expressed where

A

CNS, pituitary, thyroid, heart, adipose, skeletal muscle

~60% T4-T3 conversion

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8
Q

Type 3 (D3) deiodinase

A

predominantly expressed in the brain and skin in healthy adults
functions to INACTIVATE T3 - converts to T2 and reverse T3

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9
Q

how is iodide transported into thyroid

A

sodium-iodide symporter

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10
Q

what are the diseases caused by defective sodium-iodide symporter

A
  • symporter gene mutation (congenital hypothyroidism)

- autoimmune (Hasimoto’s) thyroiditis (autoantibodies against the symporter)

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11
Q

what enzyme leads to the synthesis of thyroid hormone from tyrosine

A

thyroid peroxidase (adds iodine and couples tyrosines)

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12
Q

what transports thyroid hormone to target cells in blood?

A

thyroxin-binding globulin (TBG)

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13
Q

how is thyroid hormone transported from colloid to blood?

A

endocytosed, fuse with lysosome, free thyroid hormone released

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14
Q

how is thyroid hormone transported into the target cells?

A
  1. simple diffusion
  2. MCT (monocarboxylate transporter family)
  3. OATP (organic anion transporting polypeptides)
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15
Q

where are MCT and OATP expressed? what are they important for?

A

expressed in liver, kidney, brain, heart

maintain intracellular concentrations of thyroid hormone

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16
Q

regulation of thyroid function (hypothalamus, anterior pituitary)

A

hypothalamus: TRH

anterior pituitary: TSH

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17
Q

TSH and T4 levels in: hyperthyroidism, hypothyroidism primary, hypothyroidism secondary

A

hyperthyroidism: TSH low and T4 high
hypothyroidism primary: TSH high and T4 low
hypothyroidism secondary: TSH low and T4 low

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18
Q

what does binding of T3 to thyroid hormone receptor lead to?

A

transcriptional regulation (activation or suppression) of thyroid hormone regulated genes

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19
Q

what hormone is released from the thyroid?

A

80% T4 and 20% T3

20
Q

symptoms of hypothyroidism

A

fatigue, depression, sensitivity to cold (lower metabolism), weight gain, goiter, muscle weakness, coarsening of the skin, dry or brittle hair, constipation, muscle cramps, increased risk of miscarriage

21
Q

hypothyroid diseases

A
  1. hashiimoto’s thyroiditis: autoimmune antibodies against thyroid peroxidase or sodium-iodide symporter or TSH receptor
  2. iodine deficiency
  3. thyroid ablation
  4. secondary (central) hypothyroidism (pituitary or hypothalamus)
22
Q

myxedema

A

severe form of hypothyroidism, mostly adult onset

23
Q

cretinism

A

infancy/childhood hypothroidism. causes mental retardation and dwarfism

24
Q

treatment for hypothyroidism

A

thyroid hormone replacement therapy

  1. levothyroxine sodium T4
  2. liothyronine sodium T3
  3. liotrix mixture of T4:T3
25
Q

what is the preferred drug for use in the treatment of hypothyroidism? how is it administered?

A 
levothyroxine sodium (T4) - longer half life and can be converted to T3 in peripheral tissues
oral administration - IV or IM for people with GI diseases
26
Q

which drug is for more acute scenarios of hypothyroidism

A

IV liothyronine - more rapidly effective (2-4 hr)

*it is also more potent than levothyroxine)

27
Q

side effects of thyroid replacement drugs

A

dose related and more quickly occur with liothyronine

  • heart palpitations
  • nervousness
  • heat intolerance
  • excessive sweating
  • insomnia
  • tremor
  • frequent bowel movements
  • excessive weight loss
28
Q

in which patients should thyroid hormone replacement be used with caution

A 
angina, coronary artery disease, hypertension 
pregnant women (need adequate doses)
29
Q

what is the most common preventable cause of mental handicap in the world?

A

iodine deficiency

30
Q

iodine sources

A

soil and water

31
Q

symptoms of hyperthyroidism

A
  • rapid heart beat
  • weight loss
  • nervousness and alertness
  • heat intolerance
  • fatigue
  • increased bowel frequency
  • loss of sleep
  • tremors
  • excessive sweating
  • exophthalmus
32
Q

grave’s disease

A

MCC hyperthyroidism

autoimmune thyroid-stimulating antibodies causing overproduction of thyroid hormone

33
Q

what are the causes of hyperthyroidism

A
  1. graves disease
  2. nodular goiter (most are benign)
  3. thyroiditis
  4. thyroid cancer
34
Q

lab findings for hyperthyroidism

A

serum TSH decreased

T3 and free T4 elevated

35
Q

hyperthyroid treatment strategies

A
  1. subtotal thyroidectomy + replacement of T4
  2. irradiate thyroid gland (radioactive iodine 131I) + replacement of T4
  3. inhibit thyroid peroxidase activity with antithyroid drugs (propylthiouracil, methimazole, carbimazole)
  4. interfere with thyroid hormone facilitation of sympathetic activite (beta blocker propranolol)
36
Q

what are the antithyroid drugs

A

propylthiouracil, methimazole, carbimazole (prodrug of methimazole)

37
Q

what is the mechanism of action of the antithyroid drugs propylthiouracil, methimazoke, carbimazole?

A

inhibits the organification of iodide and coupling of iodotyrosine causing inhibition of thyroid hormone synthesis (blocks thyroid peroxidase enzyme)

38
Q

which antithyroid drug has additional activity and what is it?

A

propylthiouracil also reduces the deiodination of T4 to T3 by inhibiting D1 deiodinase activity

39
Q

methimazole and propylthiouracil severe side effects

A

agranulocytosis, hepatitis, lupus-like syndrome

40
Q

which antithyroid drug is safer with respect to agranulocytosis?

A

methimazole

41
Q

which drug is the choice for pregnant women?

A

propylthiouracil

42
Q

people developing one of the severe side effects from antithyroid drugs are then treated with what?

A

131I or surgery since agranulocytosis, hepetitis, and SLU Like syndrome are absolute contraindications

43
Q

131 I

A

thyroid specific 131 I isotope is used to destroy sufficient thyroid tissue to restore euthyroid

44
Q

what does 131 I emit

A

gamma rays and beta particles

45
Q

how are patients with severe hyperthyroidism looking to use 131 I treated?

A

combination with antithyroid drugs or a beta blocker because effects are not seen for over 4 weeks

46
Q

contraindications for radioiodine

A

pregnancy and breast feeding

47
Q

mechanism for beta-adrenergic-antagonist drugs

which ones are used?

A

propranolol, metoprolol, atenolol, nadolol
used as adjunctive agents in patients with graves’ hyperthyroidism to control symptoms such as tremor, anxiety, palpitations

ABBEY MSII Unit 5 (8 decks)

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