1. Pharmacology of drugs used in calcium & vitamin D disorders

2. Objectives By the end of lecture, the students will be able to :
Recognize the common drugs used in calcium & vitamin D disorders
Classify them according to sources & Pharmacological effects
Detail the pharmacology of each drug , regarding , Mechanism, clinical utility in affecting calcium & vitamin D

4. BONE
Is a dynamic organ undergoes continuous remodeling process involving resorption of old bone by osteoclast & formation of new bone by osteoblast.
The dominant site of calcium storage in the body is bone, which contains nearly 99.9% of body calcium.

5. Parathyroid hormone ( PTH) Teriparatide vitamin D calcitonin
The principal agents involved in calcium metabolism & bone remodeling are :
Parathyroid hormone ( PTH)
Teriparatide
vitamin D
calcitonin
PTH and vitamin D play central roles in the regulation of bone metabolism

6. The target tissues
Bone
kidney
Intestine

7. Parathyroid Hormone
Released from the parathyroid gland in response to hypocalcemia

8. Effects of of PTH
BONE
In response to hypocalcemia , PTH stimulates osteoclast cells to increase the outward flux of calcium to restore serum calcium level.

9. Continue kidney  Ca2+ reabsorption
 formation of calcitriol which is the active form of vitamin D

10. Continue
GIT
 absorption of Ca2+

12. Continue
Daily , intermittent administration of PTH for 1 to 2 hours / day leads to a net stimulation of bone formation .
Continuous exposure to elevated PTH leads to bone resorption .

13. PTH RESPONSE TO PTH Intermittent Continuous  osteoclast
 bone resorption
 serum Ca++
 osteoblast number/function
 bone formation
 bone mass/strength
The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. In monkey studies, teriparatide improved trabecular microarchitecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, the anabolic effects of teriparatide are manifest as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. By contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation.

14. Clinical uses Treatment of severe osteoporosis
Resistance cases failed to response to other medications

15. Teriparatide
Synthetic polypeptide form of PTH. It affects calcium homeostasis in the same way as PTH.
Given daily Subcutaneous injection

16. Therapeutic uses of Teriparatide
Osteoporosis in postmenopausal women at high risk of fracture.
Hypogonadal osteoporosis in men at high risk of fracture
or treatment of osteoporosis in people who have a risk of getting fracture
Postmenopausal osteoporosis.

17. Side effects Carcinogenic effect (osteosracoma)
Diarrhea, heart burn, nausea
headache
Hypotension
Elevated serum calcium can occur in some cases can lead to kidney stones

18. Contraindications People having bone tumors Paget,s disease of bone
People who had radiation treatment involving bones
Children

19. Vitamin D Cholecalciferol ( vitamin D3) Ergocalciferol ( vitamin D2) .
Vitamin D2 is the prescription form of vitamin D & is also used as food additive.
Vitamin D3 is usually for vitamin D- fortified milk & foods & also available in drug combination products.
Both of them are routinely added to calcium supplements and milk for the purpose of preventing rickets in children and osteomalaciea in adults.

20. Sources of Vitamin D D2
Diet as in
milk
egg yolk
fish oils

21. Continue Sunshine : Cholecalciferol (D3) )
Generated in the skin from 7- dehydrocholesterol by the action of ultraviolet radiation (sunshine).

22. Vitamin D Metabolism
Liver converts vitamin D to 25-hydroxycholecalciferol
In the kidney : parathyroid hormone stimulates the formation of active form of vitamin D ( calcitriol ) { 1,25-(OH)2 D3}

23. Calcium and Vitamin D
major circulating form and principle storage form of vitamin D
Vit D3
Vitamin D increases bone resorption, increases Ca2+ absorption from the intestine, increases renal Ca2+ reabsorption, and decreases the production of PTH by the parathyroid glands. The overall effect of vitamin D is to increase plasma Ca2+ concentrations.

24. Effect of active metabolite of vitamin D
Increase serum calcium and phosphate by promoting their uptake from GIT
Increase bone resorption
Decrease renal excretion of both electrolytes
Inhibit PTH formation

25. Calcitonin
Released from the parafollicular cells (C cells) of the thyroid gland in response hypercalcemia.

26. Effects of calcitonin
Bone : Decrease bone resorption by inhibiting osteoclast activity
Kidney : Decreases reabsorption of Ca2+ & PO4 , thus increasing their excretion

27. Clinical uses of Calcitonin
Osteoporosis
Hypercalcemia
Hypercalcemia due to Paget,s disease
Routes of administration
S.C.
Nasal spray( calcitonin salmon )(

28. Adverse effects Nausea local inflammation ( injection )
Flushing of face & hands
Nasal irritation