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Spring Pharm 2 > Thyroid > Flashcards

Thyroid Flashcards

1
Q

Where does T3/T4 synthesis occur?

A

Follicle cells of the thyroid

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2
Q

Steps of T3/T4 production

A
  1. Iodide –> iodine
  2. Incorp into tyrosine residues in thyroglobulin molecules
  3. DIT/MIT made
  4. Put DIT/MITs together –> T3/T4
  5. Endocytosis into colloid droplets
  6. Lysosomes act and release T3/T4
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3
Q

D1

A

Activates T4 -> T3

Liver, kidney, thyroid

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4
Q

D2

A

Activates T4 -> T3

fat, heart, skeletal muscle, CNS

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5
Q

D3

A

Inactivates T4 -> rT3

Placenta, skin, brain

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6
Q

What can inhibit D1 activity?

A

States: Illness, low calories, fetal period, selenium deficiency, lots of fatty acids
Drugs: glucocorticoids, B blockers, PTU, amiodorone

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7
Q

What cofactor is required for all deiodinases?

A

Selenium

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8
Q

Binding of thyroid hormones

A

99% bound in plasma
T4 more highly bound than T3
Mostly TBG, a little of albumin and TBPA

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9
Q

What causes and what can happen with an increase in binding proteins?

A

Cause: estrogen, methadone, pregnancy

Free levels would fall, TSH stim, more hormone produced, normal levels achieved

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10
Q

Factors that increase binding of T4 to TBG

A

Estrogen, methadone, 5FU, heroin, liver dz, HIV

HHELM5

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11
Q

Factors that decrease binding of T4 to TBG

A

Glucocorticoids, androgens, salicylate, antisezuire meds, illness
SAAIG

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12
Q

Compared to T4, T3 is…

A

More potent
Has higher affinity for Receptor
Shorter t 1/2

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13
Q

Where is T4 absorbed best?

A

Duodenum, ileum – modified by intraluminal factors (drugs, food, flora)

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14
Q

Which is more absorbed, T3 or T4?

A

T3 - minimally affected by intraluminal binding proteins

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15
Q

Effects of non-euthyroid states on pharmacokinetics

A

Hyperthyroidism: can inc clearance of T3/T4
Hypothyroidism: can dec clearance

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16
Q

Naturally occurring isomers are in which form

A

L isomer

17
Q

Indications for thyroid replacement

A 
Adult hypothyroid (Hashimoto)
Infantile cretism (iodine def)
Endemic goiter
18
Q

Drug of choice for hypothyroid?

A

levothyroxin (T4)

19
Q

AE of levothyroxin

A

Cardiac sx - angina and palpitations, caution in elderly

20
Q

Issues with L-triiodothyronine (T3)

A

Rarely used
Short half life – take often
Expensive
Greater risk in cardiotoxicity

21
Q

Liotrix

A

Biological ratio of T4:T3 (4:1)
Not necessary, body can convert
May be good for genetic polymorphism in deiodinase enzyme

22
Q

Drug interactions with thyroid replacement therapy

A

Pregnancy (more), elderly (less) dose adjustment
Rifampin increases T4 clearance
Cholestyramine decreases GI absorption

23
Q

Major drugs for thyrotoxicosis

A

Methimazole (MMI)

Propyltiouracil (PTU)

24
Q

MMI/PTU mechanism

A

Inhibits TPO catalyze reactions to block iodide organification
Blocks coupling of iodotyrosines
PTU also blocks D1

25
Q

Onset, duration of tx of MMI/PTU

A

Slow, takes 3-4 weeks to deplete hormone

Tx for 2 years, may have permanent remission

26
Q

AE of MMI/PTU

A

Skin rash
Joint pain
Agranulocytosis
Hepatotoxic (PTU +)

27
Q

Pregnancy and hyperthyroid tx

A

PTU first trimester and nursing mothers

Then switch to MMI (MMI greater birth defects)

28
Q

What drug tx for thyroid storm

A

PTU

29
Q

Anion inhibitors MOA and AE

A

MOA: blocks thyroid uptake in those with iodide induced hyperthyroidism (amiodorone)
AE: aplastic anemia

30
Q

Iodides - use and MOA

A

with PTU and beta blocker in thyroid storm

MOA: Wolff Chaikoff effect to inhibit hormone release, decrease size of hyperplastic gland

31
Q

AE of iodide

A

Uncommon and reversible
Rash, swollen salivary glands, mucus membrane
FETAL GOITER IN PREG

32
Q

Pre-op tx for subtotal thyroidectomy

A

thioamide for 6 weeks until euthyroid
KI x 10 days to reduce size
B blocker for sx relief

33
Q

Radioactive iodide (I-131)

A

Rapidly concentrates in thyroid follicle where B articles selectively destroy gland w/o injury to adjacent cells –> 6-8 weeks
No kids or preg
80% of pts become hypothyroid

Spring Pharm 2 (5 decks)

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