Lecture 89 - Thyroid Pharm + Bone Mineral Pharm

Question 1

Describe the process of thyroid hormone biosynthesis central and peripheral

Answer 1

Iodide transport and Organification

Tyrosine iodination –> MIT, DIT by peroxidase

Coupling of MIT/DIT = t3 or t4, by peroxidase

5:1 T4:3

Exocytosis

Tranasport by TBG

Reaches target tissues where 5’ Deiodinase converst t4 –> t3

Question 2

how is thyroid hormone transported in the blood

Answer 2

TBG

Question 3

how is thyroid hormone activated in the periphery

Answer 3

T4/T3 dissociate from TBG

5’ De iodinase (in the periphery) – T4 —-> T3

Question 4

what tissues are highly responsive to thyroid hormone

which are not responsive?

Answer 4

responsive: Pituitary, Kidney, Heart, Lung, Skeletal muscle, intestines

Unresponsive: Spleen, testes

Question 5

what is the mainline treatment for hypothyroid

Answer 5

hormone supplement

Question 6

what drugs can sometimes induce hypothyroid?

Answer 6

steroids, Beta blockers

Question 7

first line medical therapy for hypothyroid?

how long does it take to see improvement?

Answer 7

Synthetic T4 - Levothyroxine –

takes a few weeks to see improvement in symptoms

Question 8

why is synthetic T4 prefered over synthetic T3?

Answer 8

T4 is less potent; less side effects and body regulates the amount it wants to convert to T3

Question 9

side effects of t3 supplements?

Answer 9

liothyronine

Hyperthyroid symptoms
Afib, tachycardia

Question 10

pathophysiology for some cases of hypothyroid during pregancy…how should you adjust the medical regimen?

Answer 10

There is an increased TBG, therefore patients may be effectively hypothyroid (need to increase dose of synthetic thyroid)

Question 11

treatment for myxedema coma

Answer 11

IV therapy – but avoid excess
Loading dose of T4 to fill the empty TBG

Then give active dose

Question 12

Toxicity of thyroid hormone replacement

Answer 12

Symptoms of Hyperthyroid

Older patients – sensitive to T4; cardiotoxicity (afib, tachycardia), osteoporosis

Question 13

two classes of drugs used to treat hyperthyroid

Answer 13

Thiomides

Anion Inhibitors:

Question 14

name three thiomides and mechanism of each

Answer 14

Carbimazole – pro drug of methimazol

Methimazol (blocks peroxidase)

Propylthiouracil (PTU): blocks peroxidase and 5’ deiodinase

Question 15

how long before effects of thiazides?

side effects of methimazole

Answer 15

Onset of action will be slow, bc stops synthesis;

May take 3-4 weeks before effects

Possible Teratogen; Agranulocytosis, Hepatotoxicity

Question 16

how do anion inhibitors work?

which anion inhibitors are used?

indications :

Answer 16

Percholate (CLO4-), Thiocyante (SCN-)

block uptake of Iodide through competitive inhibition of iodide transport mechanism

Thyroid Storm
Pre thyroidectomy

Question 17

what medical therapy is used for thyroid ablation ?

how does this work?

Answer 17

Radioactive Iodine – (I 131)

Mechanism: taken up by thyroid; secretes Beta Rays Destruction of the thyroid Parenchyma —

Question 18

contraindications for RAI

Answer 18

Pregnant or Nursing women

Question 19

what other medication may be used to help manage symptoms of thyrotoxicosis

Answer 19

Propranolol

Question 20

what drugs can be used for treatment of thyroid storm

Answer 20

Propranolol
Diltiazem (if prop can be used bc of heart failure)

Saturated Potassium Iodide

PTU

Barbiturates - T4 –> rT3

Hydrocortisone - T3 –>rT3

Question 21

how do glucocorticoids lead to stunted growth in kids and osteoporsis in adults

Answer 21

Antagonizes Vit D stimulated Calcium Transport

Stimulates renal calcium excretion

Blocks Collagen syntehsis

Increases PTH stimulated bone resorption

Question 22

How does menopause lead to bone loss?

Answer 22

Estrogen Receptors on Bone == Bone remodeling

Question 23

what drugs which act on the ER may be used to protect from bone loss?

Answer 23

SERM (Selective estrogen receptor Modulator)

such as Riloxifene

Question 24

what non hormonal therapy is used for bone stabilization

theories of its mechanism

Answer 24

Bisphosphonates

Question 25

increased risk for ____ with bisphosh use

Answer 25

Atypical Subtrochanteric femur fracture

Question 26

what antibody therapy is used for bone stabilization. how does it work?

Answer 26

RANKL inhibitor (Denosumab)
OB RANKL activates OC RANK; therefore this antibody blocks OC activaiton