Lecture 1: Thyroid Pharmacology

Question 1

What is most circulating TH bound to?

what is result of this?

Answer 1

TBG (thyroxin binding globulin) = plasma protein

- results in longer t 1/2 and low amt free hormone

Question 2

Does TBG bind to more T4 or T3? (which TH hormone has higher free levels)

Answer 2

TBG binds to more T4 –> more T3 is free

Question 3

What type of hormones can the pituitary respond to?

Answer 3

FREE hormones only

Question 4

What are 2 causes of incr thyroid binding proteins?

Answer 4

1. Drugs (estrogen, methadone)

2. Pregnancy

Question 5

What is the result on the levels of TH when incr thyroid binding proteins? (whole process)

Answer 5

TH levels incr
(less free hormone–> pituitary sees less–> incr TSH–> incr TH levels –> levels of TSH and free THs return to normal (euthyroid)

Question 6

Which isomers of thyroid hormones are naturally occurring and have more activity?

Answer 6

L-isomers

Question 7

Where is T4 best abosrbed from

Answer 7

duodenum and ileum

Question 8

How does hyperthyroidism affect clearance of T4 & T3?

Hypothyroidism?

Answer 8

Hyperythyroidism–> incr clearance T4/3 (shorter half life)

HYPOthyroidism –> decr clearance T4/3 (longer half life)

Question 9

T4 vs T3:

• which has longer half life (only need once daily dosing)
• which has more potency/affinity for receptors

Answer 9

T4 = longer half life 
T3 = more potency & affinity for rec

Question 10

What modifies the body’s secretion and degradation rates of basically ALL other hormones

Answer 10

thyroid status (hyper, hypo, eu)

Question 11

what is the physiologic effect of TH in nervous system

Others:

1. incr heart effect, carb abs, BMR, O2 consumption
2. breakdowns fats/proteins
3. promotes normal growth/skeletal devel
4. forms LDL rec

Answer 11

promotes normal brain development

Question 12

3 indications for TH replacement therapy

Answer 12

1. Adult HYPOthyroidism
2. Infantile HYPOthyroidism (cretinism)
3. Endemic Goiter

Question 13

MC type and cause of Adult HYPOthyroidism

Answer 13

MC type = primary (thyroid gland defective)

MC cause = Hashimoto’s thyroiditis

Question 14

What is Hashimoto’s thyroiditis?

What is characteristically seen w/this d/o?

Answer 14

autoimmune destruction of thyroid gland

assoc w/Abs to thyroid gland proteins

Question 15

3 main features of Infantile HYPOthyroidism

MC areas for this type of hypothyroidism?

Answer 15

1. Neuro impairement
2. deaf-mutism
3. Developmental failures

MC in iodine defic areas (prev w/screening)

Question 16

Why is Endemic goiter rare in developed countries

Tx for endemic goiter

How is full dose of TH benefical

Answer 16

b/c iodide added to salt

Dietary supplementation of iodide

Full dose TH–> may hasten regression of goiter

Question 17

Which thyroid prep has greater risk of cardiac toxicity and is CI in pts w/heart dz

Answer 17

T3

- Liothyronine sodium, L-triiodothyronine

Question 18

Which thyroid prep is ToC for replacement therapy in hypothyroidism?

Answer 18

T4

- levothyroid sodium, L-thyroxin

Question 19

What are the cardiac Sxs assoc w/T4?

What population must you use caution in w/T4?

Answer 19

palpitations, angina

caution in elderly

Question 20

what is the thyroid prep given at T4 to T3 ratio of 4:1

Answer 20

Liotrix

Question 21

Why is Liotrix not necessary for most pts

Who may it be benefical in?

Answer 21

body converts T4–> T3

may be beneficial in pts w/genetic polymorphism in deiodinase enzyme (cant convert T4–> T3)

Question 22

What 2 drugs interactions w/T4? their effects?

Answer 22

1. Rifampin (incr clearance of T4)

2. Cholestyramine (decr GI abs of T4)

Question 23

indication for ANTIthyroid therapy

Answer 23

hyperthyroidism

Question 24

What is MC form of hyperthyroidism

Answer 24

Graves dz

Question 25

What type of d/o is Grave's dz and what is characteristicially seen w/it

Answer 25

autoimmune d/o --> IgG antibodies

Question 26

Role of IgG antibodies in Grave's dz

Answer 26

IgG antibodies that bind to TSH rec/mimics its effects and stim thyroid--> incr TH levels

Question 27

Hyperthyroidism looks like sympathetic NS overactivity but how do you know its not?

Answer 27

Catecholamine levels are NOT increased

Question 28

What are the 4 main classes/types of drugs for Hyperthyroidism

Answer 28

1. Thioamide class 2. Anion inhibitors 3. Iodides 4. Radioactive Iodide

Question 29

What are the 2 drug prototypes for the Thioamide class? MOA for both?

Answer 29

1. MMI (Methimazole) 2. PTU (Propylthiouracil) MOA = blocks iodide organification (TH production) and blocks coupling of iodotyrosines

Question 30

What is the additional MOA for PTU

Answer 30

Acts peripherally to block conversion of T4 --> T3

Question 31

Why do PTU and MMI have a slow onset of action

Answer 31

mechanism = inhibit hormone synthesis --> takes 3-4 wks to deplete hormone

Question 32

3 major AEs a/w MMI and PTU Others: skin rash, joint pain

Answer 32

1. Agranulocytosis 2. Hepatotoxicity (worse w/PTU) 3. Birth defects (more w/MMI)

Question 33

Recommendation for pregnant women on taking MMI vs PTU

Answer 33

PTU in 1st trimester --> then MMI

Question 34

What dz is MMI and PTU the major drugs of Tx for?

Answer 34

Thyrotoxicosis

Question 35

What is benefit of giving high enough conc to suppress gland for 2 yrs w/MMI or PTU

Answer 35

possible permanent remission

Question 36

3 types of Anion inhibitors for Txing hyperthyroidism

Answer 36

1. Perchlorate (ClO4-) 2. Pertechnetate (TeO4-) 3. Thiocyanate (SCN)

Question 37

MOA for potassium perchlorate major use?

Answer 37

blocks thyroidal uptake of iodine Txs iodine induced HYPERthyroidism

Question 38

common drug that causes iodine induced HYPERthyroidism

Answer 38

amiodarone (iodine rich)

Question 39

Major AE a/w Anion inhibitors?

Answer 39

Aplastic Anemia

Question 40

What 2 ways do iodides work to tx hyperthyroidism

Answer 40

1. inhibit organification and hormone rel | 2. decr size of hypertrophic gland

Question 41

What do iodides precipitate

Answer 41

Wolff-Chaikoff effect

Question 42

In what situation is the Wolff-Chaikoff reversed w/ time? term for this reversal effect

Answer 42

effect reverses over time -- if iodides used ALONE escape

Question 43

When are iodides CI? why?

Answer 43

Pregnancy --> fetal goiter

Question 44

3 uncommon AEs that are usu reversible when iodides stopped?

Answer 44

1. acneiform rash 2. swollen salivary glands 3. mucous mem ulcerations

Question 45

When are iodides used? w/what other drugs | rarely used today

Answer 45

used w/PTU and b-blockers for thyroid storm

Question 46

After radioactive iodide concentrates in thyroid follicle cells what is its MOA

Answer 46

Beta particles selectively destroy thyroid gland | w/out injury to adj cells

Question 47

What is common eventual AE of radioactive iodide in most pts? 2 CIs

Answer 47

HYPOthyroidism CI = kids, preg

Question 48

What dz does radioactive iodide Tx

Answer 48

thyrotoxicosis

Question 49

2 benefits of radioactive iodide Tx

Answer 49

1. euthyroid in 6-8 wks | 2. no incr CA risk

Question 50

3 Things given for PREoperative Tx before subtotal thyroidectomy?

Answer 50

1. Thioamide drug 2. KI (potassium iodide) 3. beta blocker

Question 51

How long give Thioamide drug for PREoperative Tx before subtotal thyroidectomy?

Answer 51

til euthyroid (~6 wks)

Question 52

When give Kl as PREoperative Tx before subtotal thyroidectomy? Why?

Answer 52

10 days before surg | - decr gland size/vascularity --> decr surgical risk

Question 53

Why give beta blocker as PREoperative Tx before subtotal thyroidectomy?

Answer 53

antagonize cathecholamine effects --> sx relief