Pharm Ii Exam Ii- Thyroid/antithyroid Agents

Front 1

1. SRIF, DA and large doses of glucocorticoids inhibit _______________

Back 1

a. TRH and therefore TSH release

Front 2

1. Two main thyroid hormones

Back 2

a. thyroxine or T4
b. triiodothyronine or T3
• they are iodinated derivatives of tyrosine.

Front 3

1. Uptake of iodine is stimulated by ________and inhibited by _________

Back 3

a. Active transport system Stimulated by TSH
b. and Inhibited by ions
• Iodide
• Thiocyanate

Front 4

1. Iodide oxidized by ________to active form

Back 4

a. thyroid peroxidase
• iodide has to be oxidized before it can be attached to tyrosyl residues in thyroglobulin

Front 5

1. thyroid hormone precursors:

Back 5

a. monoiodotyrosine (MIT) and
b. diiodotyrosine (DIT)

Front 6

1. what thyroid hormone precursors make up T3

Back 6

a. MIT + DIT = T3

Front 7

1. what thyroid hormone precursors make up T4

Back 7

a. DIT +DIT = T4

Front 8

1. Where is T4 converted into T3

Back 8

a. T4 is converted to T3 primarily in liver
• Chronic alcoholics cant convert T4T3

Front 9

1. which thyroid hormone is more active…T3 or T4?

Back 9

a. T3 is 5 times more active than T4

Front 10

1. What enzyme is used to convert T4 into T3

Back 10

a. 5'-deiodinase
• Enzyme found in liver, kidney and thyroid

Front 11

1. T4 and T3 transported bound to

Back 11

a. thyroxine binding globulin (TBG)
• T4 binds to TBG with greater affinity
• Binding to plasma proteins protects thyroid hormones from metabolism

Front 12

1. Metabolism and excretion of thyroid hormones occurs where?

Back 12

a. Metabolized in liver
b. Excreted in feces

Front 13

1. Biological actions of thyroid hormone are mediated through___________

Back 13

a. Mediated through nuclear T3 receptors
• Alter gene expression

Front 14

1. Function of thyroid hormone

Back 14

a. Brain development & protein synthesis
b. Very important in the development of the fetus

Front 15

1. Cardiovascular effects of thyroid hormone

Back 15

a.Increase heart rate,
b. Increase cardiac index,
c.Decrease vascular resistance

Front 16

1. Thyroid hormone drugs include

Back 16

a. Thyrotropin
b. thyrogen
c. Levothyroxine
d. Liothyronine
e. Liotrix
f. Thyroxine???

Front 17

1. Thyrotropin is an analog to what hormone

Back 17

a. TSH
• Bovine in nature
• Used mostly for dx purposes

Front 18

1. Thyrogen is an analog to what hormone

Back 18

a. Recombinant form of TSH

Front 19

1. Levothyroxine is an analog to what hormone

Back 19

a. T4

Front 20

1. Liothyronine is an analog to what hormone

Back 20

a. T3

Front 21

1. Liotrix is an analog to what hormone

Back 21

a. (combination of T4 and T3; 4:1)

Front 22

1. Thyroxine is an analog to what hormone?

Back 22

a. (T4) is drug of choice
• Longer duration of action
• Most individuals (as long as their liver woks) giving T4 is enough

Front 23

1. 2 forms of TSH

Back 23

a. Thyrotropin-- from bovine anterior pituitary
b. Thyrogen: --recombinant form of TSH

Front 24

1. Clinical use of TSH and its analogs

Back 24

a. Hypothyroidism diagnosis
• --Differentiate between 1° and 2° hypothyroidism
b. Thyroid carcinoma
• --Enhances uptake of 131I by thyroid gland

Front 25

1. How is TSH used to differentiate between 1° and 2° hypothyroidism

Back 25

a. If there is no elevation in T3 and T4 after you give TSH the problem is at the thyroid
b. If there is a elevation in T3 and T4 after you give TSH then the problem is the anterior pituitary

Front 26

1. Pharmicokinetics of TSH and its analog

Back 26

a. IM or SC administration
b. Half-life: 35 minutes (both forms are short acting)
c. Excreted in urine

Front 27

1. Adverse effects of TSH and its analog

Back 27

a. Nausea/vomiting, headache, fever
b. Sinus tachycardia, atrial fibrillation
• -----If you give this to a person with consistently low thyroid levels you will see cardiovascular effects
• -----A spike in thyroid levels could  irregular heart rates

Front 28

1. Contraindications of TSH and its analog

Back 28

a. Coronary artery disease
b. Adrenal insufficiency

Front 29

1. Drug interactions of TSH and its analog

Back 29

a. Sympathomimetics: additive effect
• -----Increase in rate and force of contraction (CV)
• -----Increase cardiac output
b. Hepatic enzyme inducers:
• -----Barbiturates, rifampin, carbamazepine
1. ---------------TSH gets metabolized quicker if on these
c. Estrogens increase levels of TBG

Front 30

1. Clinical use of T3 and T4

Back 30

a. Hypothyroidism – replacement therapy
• T3 can be used when faster onset of action needed
• T3 more expensive, requires frequent dosing
• No advantages to using T3/T4 mixture

b. Cretinism v. myxedema
• Thyroid hormone in the fetal brain causes lots of neural migration
• If you don’t have THYROID HORMONE IN FETAL BRAIN  CREATISM
• Mixedema can occur post partum in the developing brain if you have low thyroid hormone
• Replacement of thyroid hormone reverses these effects

c. TSH Suppression
• Nodular thyroid disease
• Diffuse goiters
• Thyroid cancer

Front 31

1. What must happen to Levothyroxine before it becomes active?

Back 31

a. Levothyroxine must be converted to T3 for clinical effect

Front 32

1. Half Life of T3 and T4

Back 32

a. T3-1day,
b. T4-7 days

Front 33

1. How long does it take T4 to achieve a steady state

Back 33

a. 4-6 weeks

Front 34

1. ROA for T3 and T4

Back 34

a. Oral administration (~80% bioavailability)
• Metabolized in liver, excreted in feces
• Children may require higher doses per Kg body weight

Front 35

1. Adverse effects of T3 and T4

Back 35

a. Headache, insomnia, tremors, fever
b. Cardiac dysrhythmias, tachycardia
c. Diarrhea, weight loss, amenorrhea

Front 36

1. Contraindications of T3 and T4

Back 36

a. Adrenal insufficiency
b. Cardiac disease

Front 37

1. Drug interactions with T3 and T4

Back 37

a. Warfarin: Increases anticoagulant activity
b. Bound by cholestyramine in GI tract
• ----Also Al(OH)2 and FeSO4 (iron supplements) and sucralfate

c. Drug interactions with TBG
• Increase binding: estrogens, tamoxifen
• Decrease binding: aspirin, phenytoin, furosemide, androgens, carbamazepine

d. Hepatic enzyme inducers:
• Barbiturates, rifampin, carbamazepine

Front 38

1. Antithyroid drug categories include

Back 38

a. THIOUREYLENES
b. Iodide
c. Iodinated contrast media

Front 39

1. THIOUREYLENE drugs include

Back 39

a. Propylthiouracil (PTU)
b. Methimazole
c. Carbimazole

Front 40

1. Iodide drugs include

Back 40

a. Lugol’s solution
b. Potassium iodide

Front 41

1. Iodinated contrast media includes

Back 41

a. Ipodate & iopanoic acid = oral administration
b. Diatrizoate = IV

Front 42

1. MOA of THIOUREYLENES

Back 42

a. Inhibits thyroid peroxidase-mediated iodination (PRIMARY)
b. Inhibits coupling of MIT and DIT
c. Inactivates oxidized form of thyroid peroxidase
d. Propylthiouracil (PTU) inhibits peripheral conversion of T4 to T3

Front 43

1. Clinical use of THIOUREYLENES

Back 43

a. Hyperthyroidism
• Graves disease
• Hyperfunctioning thyroid nodules
• Thyroid storm
---------------Propylthiouracil drug of choice

b. Treatment paradigms
• Antithyroid drugs
---------------Treatment of choice during pregnancy
• Drugs + radioactive iodine
• Drugs + surgery

Front 44

1. ROA for THIOUREYLENES

Back 44

a. Oral administration

Front 45

1. THIOUREYLENES are actively concentrated where in the body

Back 45

a. Actively concentrated in thyroid gland

Front 46

1. Half life of THIOUREYLENES

Back 46

a. PTU has shorter half-life (2 v. 7 hr), plasma protein bound
• Methimazole given once a day
• Metabolized in liver, renal excretion

Front 47

1. ADVERSE EFFECTS THIOUREYLENES

Back 47

a. Headache, vertigo, edema
b. N/V
c. Rash: urticaria, pruritus, alopecia
d. *Methimazole: agranulocytosis, aplastic anemia
e. Reduces response to oral anticoagulants

Front 48

1. MOA of iodide

Back 48

a. Inhibition of release of thyroid hormones
• Rapid effect
• Action directly on thyroid gland

b. Limits transport of iodide into thyroid
c. Inhibits synthesis of MIT and DIT

Front 49

1. Clinical use of iodide

Back 49

a. Hyperthyroidism
• Preoperative period in preparation for surgery
• Thyroid storm

Front 50

1. ROA of iodide

Back 50

a. Administered orally
• Lugol’s solution
• Potassium iodide

b. Rapid effect, accumulates in thyroid

Front 51

1. This antithyroid hormone develops tollerence after 2-3 days

Back 51

a. iodide

Front 52

1. Adverse effects of iodide

Back 52

a. Nausea/vomiting, diarrhea
b. *Acneiform rash
c. *Hypersensitivity (Type III)
• Angioedema, hemorrhage
d. *Induction of goiter and myxedema

Front 53

1. Drug interactions of iodide

Back 53

a. Lithium

Front 54

1. Components of IODINATED CONTRAST MEDIA

Back 54

a. Ipodate & Iopanoic acid - Oral
b. Diatrizoate - IV

Front 55

1. Clinical use of iodinated contrast media

Back 55

a. Hyperthyroidism
b. Inhibits conversion of T4 to T3
• (not approved by the FDA for this)
• Euthyroid in 3 days
• Suppresses T4 also
• Inhibits release of hormones

Front 56

1. MOA of radioactive Iodide

Back 56

a. Trapped by thyroid
b. Deposited in the follicle
c. Acts almost exclusively on parenchymal cells
d. ***Destroys thyroid w/o damage to surrounding tissue

Front 57

1. Clinical use of radioactive iodide

Back 57

a. Hyperthyroidism
• Poor surgical subjects
• Additional tx when subtotal thyroidectomy ineffective
• Toxic nodular goiter

Front 58

1. ROA of radioactive iodide

Back 58

a. oral

Front 59

1. Half-life of radioactive iodide

Back 59

a. 8 days
• 99% radiation lost w/I 56 days

Front 60

1. Adverse effects of radioactive iodide

Back 60

a. High incidence of delayed hypothyroidism
b. Long tx period

Front 61

1. Contraindications of radioactive iodide

Back 61

a. Pregnancy