Pharm- Thyroid

Front 1

What are the five molecules in the synthesis of T4

Back 1

MIT, DIT, Reverse T3, T3, T4

Front 2

Five major steps of TH synthesis

Back 2

1. Uptake of I
2. Oxidation/activation of I
3. Coupling into Tg
4. Storage
5. Proteolysis and release.

Front 3

Cell to plasma ratio

Back 3

20-40:1

Front 4

How does oxidation occur

Back 4

H2O2 reacts with TPO to oxidize it.

Front 5

How does iodination occur.

Back 5

Oxidized Iodine attacks Thyroglobulin forming MIT and DIT. This causes thyroglobulin to change form to put tyrosine residues on TG close together to make T4 of T3.

Front 6

How does coupling work

Back 6

TPO and H2O2 are in close proximity with MIT or DIT and they cause synthesis of T4 or T3. This is a peptide bond. MIT and DIT monomers can still exist.

Front 7

How does storage occur?

Back 7

Moves from follicular cell to colloid. Takes a long time of stopping synthesis for any plasma drop in thyroid hormone.

Front 8

How does proteolysis and release of TH occur.

Back 8

Lysosomes fuse with colloid droplets and form phagolysosome and move toward basal membrane. These lyse Thyroglobulin (Tg) and release T3 or T4.

Front 9

What happens to uncoupled MIT and DIT.

Back 9

They are deiodinized by an enzyme and the Iodine in recycled.

Front 10

What does 5' deiodinase do.

Back 10

Converts T4 to T3 before release into plasma.

Front 11

TBG- thyroxine binding globuline

Back 11

Binds T4 and T3. A decrease in TBG can cause hyperthyroidism.

Front 12

TBPA-thyroxine binding prealbumin

Back 12

Only binds T4

Front 13

Albumin

Back 13

Binds to T3 and T4. If knocked off can cause hyperthyroidism

Front 14

What happens if you block 5'-deiodination

Back 14

You would get relative hypothyroidism because of the lost ability to go from T4 to T3.

Front 15

What are some agents that block deiodination.

Back 15

Propylthiouracil, iopanoic acid, amiodarone, propranolol, pharmacological doses of glucocorticoids.

Front 16

Neonate hypothyroidism is called what and what are the symptoms.

Back 16

Cretinism. Physicologic jaundice, constipation, somnolence, feeding problems. Screen them.

Front 17

What does hypothyroidism look like in young children.

Back 17

Protruding tongue, broad flat nose, wide set eyes, dry skin, coarse hair, impaired mental development, retarded bone growth

Front 18

What does hypothyroid look like in older kids

Back 18

retardation of growth, Delayed puberty, poor school performance.

Front 19

What does hypo look like in adults.

Back 19

fatigue, lethargy, constipation, slowing of central and muscular activity, decreased appetite, increased weight, deeper, hoarse voice, severe myxedema (doughy cool skin, enlarged heart, coma)

Front 20

What are some other diseases that might make you think hypothyroid?

Back 20

123I uptake is low. elevated choleserol (primary), eleavted CPK and ALD, pernicious anemia.

Front 21

With someone who has an endemic goiter, how do you want to treat them?

Back 21

Give synthetic T4 to inhibit TSH and then give iodine to prevent rebound hyperthyroidism.

Front 22

What is the daily T4 output and how much do we need to supplement for hypo.

Back 22

Daily is 80 micrograms and give 150-200 micros to make up for varied absorption.

Front 23

Thyroid USP

Back 23

Organic TH extract. Powder from animal thyroid glands. Calibrated by iodine contents. Not bioassayed because of batch to batch variation. Synthetics preferred b/c of immune response and safety issues.

Front 24

Thyroglobulin USP

Back 24

Purified from pig thyroid. Contasins USP standard iodide content. Is bioassayed. Synthetic preferred because of immune response and variability and safety issues.

Front 25

Levothyroxine

Back 25

Drug of choice for hypothy. L isomer of T4. More uniform than USP. Provides large pool of T4 to convert to T3. T3 profiles more uniform than with T3 administration.

Front 26

Liothyronine

Back 26

T3. Used if they have deficiency in deiodination.

Front 27

Liotrix

Back 27

Misture of levothyroxine and liothyronine (4:1 T4:T3). Tries to mimic thyroid output. Little advantate to levothyroxine.

Front 28

Methimazole and Propylthiouracil (PTU)

Back 28

Thiourea derivatives.Inhibit organification and coupling steps by inhibiting thyroid peroxidase. PTU also inhibits peripheral dediodination of T4 and T3.

Front 29

Methimazole PTU comparison

Back 29

PTU more rapidly absorbed although both are fast.
PTU 1.5 half life, Methimazole 6 hours
Dosing time- PTU-6, Methimazole-24 hours.
Both cross placental barrier.

Front 30

Why does anti-hyperthyroid drugs take a while to act.

Back 30

They have to deplete the stores first. It's hard to dose the patients and can often cause hypo.

Front 31

Toxic affects of methim and TPU

Back 31

Lupus like symptoms. Agranulocytosis. Cross-sensitivity to other similar drugs. Usually reversible with cessation.

Front 32

Perchlorate, Pertechnetate, Thiocyanate.

Back 32

Monovalent anion inhibitors. They block the iodine uptake by the follicular cells. Large doses can overcome the blockade.

Front 33

What is the drug of choice in amiodarone-induced hyperthyroidism (iodine induced thyrotoxicosis)?

Back 33

Perchlorate.

Front 34

How is Iodine usually given medicinally?

Back 34

You give it attached to something else (potassium, sodium) and it is reduced in the GI tract.

Front 35

How does Iodine help in hyperthyroid?

Back 35

Decreases release of T3,4 at level of proteolysis. Reduced vascularity of the hyperfunctioning thyroid. Inhibits organification of iodide in Wolff-Chaikoff effect which decrease TH synthesis. Benefits are rapid but there is also rapid resistance.l

Front 36

Iodinated contrast media.

Back 36

Used mainly for diagnosis of thyroid diseases but also in thyroid storm. Inhibits peripheral deiodination. Also suppresses T3,4 production. Used in conjunction with thioamide.

Front 37

I-131

Back 37

B emitter with half-life of 8 days. Destroy surrounding follicular tissue. Decrease the hormone synthesis. Drawbacks are potential hypothy.Crosses placental barrier. Need to be on replacement therapy for rest of life.

Front 38

Why give B blockers in hyper

Back 38

Decrease side affects of high TH. Propanolol is drug of choice. Besides symptoms it also inhibits peripheral deiodination. Withdrawn as levels normalize.

Front 39

Thyroid storm

Back 39

Severe acute Hyperthyroidism. Happens after some type of stress be it surgery, infection, or just stressed out (Desert Storm). Want to protect heart mainly. Give propanolol, iodine, and PTU. Maybe anti-pyretics, HF, and treat underlying cause.