Lecture 49 Pth Vitd Bone Drugs

Front 1

1. Describe what parathyroid hormone is and how it regulates calcium plasma levels

Back 1

• Single chain of 84 amino acids
• Action – maintain calcium plasma levels at 10mg%
• Mechanism –
o Increases calcium mobilization from bone to plasma
 Binds to osteoblasts; the hormone-osteoblast complex activates osteoclast. This occurs because receptors on osteoblasts stimulate the activity of osteoclasts, releasing Ca2+ from bone.
o Increase calcium reabsorption in renal tubules
 PTH acts directly on kidney to decrease the renal tubular reabsorption of phosphate and increase the tubular reabsorption of calcium. This leads to increase in plasma calcium levels.

Front 2

2. Describe Forteo in terms of what it is, approved use, mechanism of action and how administered.

Back 2

• Teriparatide (Forteo) is a recombinant formulation of endogenous PTH, containing a 34 amino acid sequence which is identical to the N-terminal portion of this hormone.
• The pharmacologic activity of teriparatide is similar to the physiologic activity of PTH.
• It is approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture and the treatment of primary or hypogonadal osteoporosis in men at high risk of fracture.
• Forteo works by
o stimulating osteoblast function
o increasing GI calcium absorption
o increasing renal tubular reabsorption of calcium
• Treatment with teriparatide increases bone mineral density, bone mass, and strength. In postmenopausal women, it has been shown to decrease osteoporosis – related fractures.
• It is administered by subcutaneous injection into the thigh or abdominal wall. Suggested frequency of dosing is once daily. This drug is very expensive.

Front 3

3. Name the agent that is thought to be the reverse of parathyroid hormone and its use and mechanism of action.

Back 3

• Thyrocalcitonin (Calcitonin)
o Single chain polypeptide, 32 amino acids
o Reverse of PTH
o Secreted by parafollicular cells of thyroid gland
o Decreases plasma calcium and phosphate levels
o Blocks removal of calcium from bone (by inhibiting activity of osteoclasts)
o Used in medicine to treat hypercalcemia

Front 4

4. Describe the 2 effects of vitamin D on calcium metabolism.

Back 4

1,25 – dihydroxyvitamin D increases absorption of dietary calcium and phosphate from GI tract
(PTH stimulates the formation of 1,25 – dihydroxyhormone in the kidney. Vitamin D is involved in enhancing the actions of parathyroid hormone on bone osteoblasts. Receptors present on osteoblastic cells are stimulated by parathyroid hormone. Vitamin D stimulates this effect of parathyroid hormone to produce an anabolic effect of calcium deposition in bone.)
Vitamin D and bone – two actions
• Enhances osteoblastic activity to increase uptake of calcium into bone
• 1,25 – dihydroxyvitamin D stimulates the differentiation of osteoclasts in bone matrix

Front 5

5. Describe the mechanism of action of the SERMs as used to prevent osteoporosis.

Back 5

SERMS – Raloxifene (Evista)
• The “designer” estrogen activates estrogen receptors in bone to prevent osteoporosis.
• Does not activate estrogen receptors in breast, thus helping to prevent breast cancer
• Designed to preserve beneficial effects of estrogens including protection against CV disease, and osteoporosis, but have no undesired effects on reproductive organs.
• Summary of effects:
o Anti-resorptive action on bone (calcium retained in bone matrix)
o Absence of endometrial and breast stimulation compared to natural estrogen

Front 6

6. Name the one SERM drug that is used to prevent osteoporosis and list the side effects of this drug.

Back 6

Raloxifene (Evista)
• Used to prevent osteoporosis in postmenopausal women
• Most common side effects: hot flashes, leg cramps