Lecture pharmacology of calcium metabolism

1. Pharmacology of calcium
metabolism
Gyanendra Raj Joshi PharmD, RPh

2. Objectives:
Function / Physiological roles of calcium.
Calcium and salts as drug
Control of calcium metabolism.
Parathyroid hormone.
Calcitonin.
Vitamin D.
Drugs affecting calcium metabolism.

3. Calcium is required for:
•Muscle and nerve functional integrity.
•Cardiac function.
•Coagulation of blood.
•Cementing substance of the bones.
Daily requirements: 0.5-0.75g/day. It increases during
pregnancy and lactation.
Normal serum calcium: 9 -11mg%. 6 - 6.5 mg% exists in
ionized form, which is the active form.

5. Absorption and Excretion
•Absorption- facilitated diffusion, carrier
mediated active transport
•Filtration
•Reabsorption
•Excretion

6. Preparations
1)Calcium chloride
2)Calcium gluconate
3)Calcium lactate
4)Calcium dibasic
phosphate
5)Calcium carbonate
Adverse effects :
GI side effects :
constipation, bloating ,
and excess gas
Irritation
Tissue necrosis

7. Uses:
•As a supplement during pregnancy and lactation
or when dietary calcium is low.
•Osteomalacia and osteoporosis.
•Hypoparathyroidism.
•Acute tetany: 10-20 ml calcium gluconate 10% i.v
in emergency.
•Cal gluconate in dermatoses , paresthesias ,
weakness
•As antacid

8. Control of Calcium Metabolism
•Vitamin D
•Calcitonin
•Parathyroid hormone.

9. Vitamin D
•It is a fat-soluble vitamin.
•Normally, adults do not require vitamin D.
•Children and female during pregnancy and lactation require
400-800 units/day.
Forms of vitamin D:
•Vit.D2 (ergocalciferol): it is of plant origin & formed by
ultraviolet irradiation of ergosterol in plants.
•Vit.D3 (cholecalciferol): it is made by ultraviolet irradiation of
7-dehydrocholesterol. It is the form presents in natural foods
and is formed in the skin.
•Vitamin D1: mixture of antirachitic substances

10. Activation of vitamin D:
• D2 & D3 are made active by two hydroxylation reactions:
•25-hydroxylation in the liver to 25-OH-cholecalciferol
(calcifediol).
•1α-hydroxylation in the kidney under the influence of
parathyroid hormone to 1α- 25(OH)2 cholecalciferol
(calcitriol).
•Absence or deficiency of hydroxylase enzyme in the kidney
causes renal rickets.
•Renal rickets is treated with (1α-hydroxycholecalciferol) =
alfacalcidol (one alpha).

11. Functions of vitamin D:
•Increases absorption of calcium & phosphate
from intestine.
•Increases reabsorption of calcium &
phosphate from renal tubules.
•It deposits calcium into bone.
•It raises plasma calcium and phosphate.
•Increases excretion of magnesium in the
urine.

12. Uses:
•Rickets and osteomalacia. In renal failure & renal rickets use
1α-OH- cholecalciferol (alfacalcidol or one-alpha) that needs
only hepatic hydroxylation to be more active (1α- 25(OH)2
cholecalciferol)
•Pregnancy and lactation
•Hypoparathyroidism.
•Hypophosphatemia.
•Osteoporosis.
•Fanconi Syndrome
•Psoriasis: local vitamin D (creams or ointments) preparation is
available.
Adverse reactions:
Hypervitaminosis-D: hypercalcemia, hypercalciuria and
soft tissue calcification especially in the kidney & blood vessels
(calcinosis)

13. Forms available for clinical uses include
1. Natural forms:
•D2 = ergocalciferol. It is of plant origin.
•D3 = cholecalciferol. It is of an animal origin and
formed by sunrays in the skin.
2. Active metabolites:
•Calcitriol.
•Alfacalcidol or one-alpha (1α- OH- cholecalciferol)
3. Vit. D analogue
•Dihydrotachysterol.

14. Calcitonin
It is a hormone secreted by C-cells of the thyroid gland.
Mechanism:
•GPCR, increase cAMP
Role :
•It inhibits osteoclasts  reduces bone resoption.
•It reduces re-absorption of calcium & phosphorus in the kidney.
•Lowering serum calcium.
•It also has an analgesic effect in Paget’s disease, metastatic bone
cancer and after vertebral fracture due to osteoporosis.
Source:
•Natural sources (pork, salmon, eel).
•Synthesizes.
Preparation:
It is available as solution for s.c, i.m injection and as nasal
spray.

15. Uses:
•Hypercalcemia
–Hyperparathyroidism
–Hypervitaminosis
–Malignancy
•Postmenopausal osteoporosis.
•To promote healing of bones
•Paget’s disease
•Metastatic bone cancer pain.
Adverse effects:
•Allergy, flushing, nausea, vomiting, and tingling of face & hands.
•Bad taste
•May interfere with action of Digoxin

16. Parathyroid hormone
•Secreted by parathyroid glands
–Rapid response to reduced calcium (minutes)
•Polypeptide
–84 amino acid residues
–9,500 daltons M.W.
•Peptide fragments can be active for periods
measured in hours
•Operates in tissues via cAMP second
messenger

17. Functions:
•Increasing absorption of calcium from the intestine through
activation of vitamin D in the kidney.
•Increasing reabsorption of calcium from the distal convoluted
tubule in the kidney.
•Increasing mobilization of calcium from bones to blood through its
binding to osteoblast  RANKL  stimulation of osteoclasts 
enhance bone resorption (normal bone destruction)
•Increasing excretion of phosphates in the urine.
Uses:
Parathyroid hormone has no valid use. For hypoparathyroidism
vitamin D and calcium are quite effective.

18. Hypoparathyroidism
•Low plasma Ca levels
•Tetany
•Convulsions
•Laryngospasm
•Paresthesia
•Cataract
•Psyciatric changes
•Pseudohypoparathyroidism
Hyperparathyroidism
•Hypercalcemia
•Decalcification of bone
•Renal stones
•Muscle weakness
•Constipation
•Anorexia
•Metastatic calcification

19. Bisphosphonates
•Most effective antiresorptive drugs
•3 generations :
–First generation: etidronate, tiludronate
–Second generation: Pamidronate, alendronate
–Third generation: risedronate, zoledronate
•Uses:
–Osteoporosis
–Pagets disease
–Hypercalcemia of malignancy
–Osteolytic bone metastasis

20. Other Drugs Affecting Calcium Metabolism
•Estrogen: inhibits PTH-stimulated bone resorption, so it can
prevent or delay bone loss in postmenopausal women. It is
used in postmenoposal osteoporosis (unless contraindicated).
•Glucocorticoids: chronic systemic use causes protein
catabolism and increase calcium excretion leading to
osteoporosis. It is of benefit in treatment of hypercalcemia.

21. •Fluoride: as additive in drinking water and in
dentifrice, it prevents dental caries. Chronic
ingested high concentration of the ion leading
to new bone synthesis.
•Mithramycin(Plicamycin): decreases serum
calcium in Paget's disease and reduces
hypercalcemia associated with cancer. It
inhibits bone resorption (inhibits the
osteoclasts).

22. •Thiazides: inhibit excretion of calcium. Used
to reduce kidney stone formation.
•Furosemide plus saline infusion: enhance
Calcium excretion  Decreases serum
calcium and used in acute hypercalcemia.

23. Probable questions :