LT1: PTH & treatment of osteoporosis

Question 1

What is PTH?

Answer 1

Single chain polypeptide of 84 aa, secreted by the parathyroid gland.

Question 2

What is the function of PTH?

Answer 2

Regulation of plasma conc. of Ca & phosphorus.

Question 3

How PTH maintain plasma Ca level?

Answer 3

1) Mobilizing Ca from bone.
2) Reabsorption of Ca by kidney while low phosphate reabsorption.
3) Stimulate 1,25 dihydroxyvitamin D3 production that increases Ca & phosphate absorption from intestine (& act w/ PTH to mobilize bone Ca & high Ca reabsorption by kidney.)

Question 4

How can PTH mobilize Ca from bone?

Answer 4

1- Stimulation of recruitment of osteoclast (increasing their number & activity).

2- Act on osteoblasts, leading to RANKL, which acts on osteoclasts & their precursors, increasing their number & activity, causing increase bone remodeling.

Question 5

What is the action of teriparatide on cells?

Answer 5

Higher the number & activity of the cells & lower apoptosis of osteoblasts, leading to high bone mass, structuraln integrity, & strength.

Question 6

What is teriparatide MOA?

Answer 6

act on G-protein dependent PTH receptor 1 in target cell membrane, activating adenylate cyclase, which activates phospholipase A,C,D, leading to high intracellular Ca & cAMP.

Question 7

What is the half-life of teriparatide?

Answer 7

IV=10 min, SC=1 hr.

Question 8

What are the adverse effects of Teriparatide?

Answer 8

Nausea, dizziness, headache, arthalgias, transient orthostatic hypotension, leg cramps, mild hypercalcemia (reduce the dose).

Question 9

What are contraindications of teriparatide?

Answer 9

1- Nephrolithiasis.
2- Gout.
3- Metabolic diseases (renal osteodystrophy or primary hyperparathyroidism).

Contraindicated bcz of increased risk of osteosarcoma.

Question 10

What are usage of teriparatide?

Answer 10

Treat osteoporesis in post-menopausal men & women for only 2 yrs to avoid osteosarcoma ( To prevent withdrawal bone loss, biphosphate is given at the end of the course ).