Pharmacology of calcium
Gyanendra Raj Joshi PharmD, RPh
Function / Physiological roles of calcium.
Calcium and salts as drug
Control of calcium metabolism.
Drugs affecting calcium metabolism.
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.
Absorption and Excretion
• Absorption- facilitated diffusion, carrier
mediated active transport
1) Calcium chloride
2) Calcium gluconate
3) Calcium lactate
4) Calcium dibasic
5) Calcium carbonate
Adverse effects :
GI side effects :
constipation, bloating ,
and excess gas
• As a supplement during pregnancy and lactation
or when dietary calcium is low.
• Osteomalacia and osteoporosis.
• Acute tetany: 10-20 ml calcium gluconate 10% i.v
• Cal gluconate in dermatoses , paresthesias ,
• As antacid
Control of Calcium Metabolism
• Vitamin D
• Parathyroid hormone.
• It is a fat-soluble vitamin.
• Normally, adults do not require vitamin D.
• Children and female during pregnancy and lactation require
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
Activation of vitamin D:
• D2 & D3 are made active by two hydroxylation reactions:
• 25-hydroxylation in the liver to 25-OH-cholecalciferol
• 1α-hydroxylation in the kidney under the influence of
parathyroid hormone to 1α- 25(OH)2 cholecalciferol
• Absence or deficiency of hydroxylase enzyme in the kidney
causes renal rickets.
• Renal rickets is treated with (1α-hydroxycholecalciferol) =
alfacalcidol (one alpha).
Functions of vitamin D:
• Increases absorption of calcium & phosphate
• 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
• 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
• Pregnancy and lactation
• Fanconi Syndrome
• Psoriasis: local vitamin D (creams or ointments) preparation is
Hypervitaminosis-D: hypercalcemia, hypercalciuria and
soft tissue calcification especially in the kidney & blood vessels
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:
• Alfacalcidol or one-alpha (1α- OH- cholecalciferol)
3. Vit. D analogue
It is a hormone secreted by C-cells of the thyroid gland.
• GPCR, increase cAMP
• 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.
• Natural sources (pork, salmon, eel).
It is available as solution for s.c, i.m injection and as nasal
To promote healing of bones
Metastatic bone cancer pain.
• Allergy, flushing, nausea, vomiting, and tingling of face & hands.
• Bad taste
• May interfere with action of Digoxin
• Secreted by parathyroid glands
– Rapid response to reduced calcium (minutes)
– 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
• 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.
Parathyroid hormone has no valid use. For hypoparathyroidism
vitamin D and calcium are quite effective.
• Most effective antiresorptive drugs
• 3 generations :
– First generation: etidronate, tiludronate
– Second generation: Pamidronate, alendronate
– Third generation: risedronate, zoledronate
– Pagets disease
– Hypercalcemia of malignancy
– Osteolytic bone metastasis
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.
• 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
• 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.