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Chapter: Essential pharmacology : Drugs Affecting Calcium Balance

After C, O, H and N, calcium is the most abundant body constituent, making up about 2% of body weight: 1–1.5 kg in an adult. Over 99% of this is stored in bones, the rest being distributed in plasma and all tissues and cells. Calcium serves important physiological roles.



After C, O, H and N, calcium is the most abundant body constituent, making up about 2% of body weight: 1–1.5 kg in an adult. Over 99% of this is stored in bones, the rest being distributed in plasma and all tissues and cells. Calcium serves important physiological roles.


Physiological Roles


1.   Calcium controls excitability of nerves and muscles and regulates permeability of cell membranes. It also maintains integrity of cell membranes and regulates cell adhesion.


2.   Ca2+ ions are essential for excitation-contraction coupling in all types of muscle and excitation-secretion coupling in exocrine and endocrine glands, release of transmitters from nerve ending and other release reactions.


3.   Intracellular messenger for hormones, autacoids and transmitters.


4.   Impulse generation in heart—determines level of automaticity and AV conduction.


5.   Coagulation of blood.


6.   Structural function in bone and teeth.


Plasma Calcium Level


It is precisely regulated by 3 hormones almost exclusively devoted to this function, viz. parathormone (PTH), calcitonin and calcitriol (active form of vit D). These regulators control its intestinal absorption, exchange with bone and renal excretion as summarized in Fig. 24.1. In addition, several other hormones, metabolites and drugs influence calcium homeostasis (see box).



Normal plasma calcium is 9–11 mg/dl. Of this about 40% is bound to plasma proteins—chiefly albumin; 10% is complexed with citrate, phosphate and carbonate in an un-dissociable form; the remaining (about 50%) is ionized and physiologically important. For example, in hypoalbuminemia, total plasma calcium may be low but the concentration of Ca2+ ion is usually normal. Acidosis favours and alkalosis disfavours ionization of calcium: hyperventilation precipitates tetany and laryngospasm in calcium deficiency by reducing ionization.



Calcium Turnover


Major fraction of calcium in the bone is stored as crystalline hydroxyapatite deposited on the organic bone matrix osteoid, while a small labile pool is in dynamic equilibrium with plasma. Even the fully laid down parts of the bone undergo constant remodeling by way of two closely coupled but directionally opposite processes of resorption and new bone formation (Fig. 24.2). Millions of tiny remodeling units are working on the surface of bone trabeculae and Haversian canals to dig micropits by osteoclastic activity and then repair by osteoblastic activity in which first collagen and other proteins (osteoid) are deposited followed by mineralization; the full cycle taking 4–6 months. Diet, exercise, several hormones and drugs regulate the number and efficiency of bone remodeling units at any given time. Remodeling deficits accumulate over lifetime to account for age related bone loss, the pace of which can be retarded or accelerated by modulating the above listed influences. Estrogen lack after menopause mainly causes loss of trabecular bone, particularly affecting vertebrae, wrist bones and femoral neck. Minimal trauma/compression fractures are most common at these sites.



Absorption And Excretion


Calcium is absorbed by facilitated diffusion from the entire small intestine as well as from duodenum by a carriermediated active transport under the influence of vit D. Phytates, phosphates, oxalates and tetracyclines complex Ca2+ in an insoluble form in the intestines and interfere with absorption.

Glucocorticoids and phenytoin also reduce calcium absorption.


All ionized calcium is filtered at the glomerulus and most of it is reabsorbed in the tubules. Vit D increases and calcitonin decreases proximal tubular reabsorption, while PTH increases distal tubular reabsorption of Ca2+. About 300 mg of endogenous calcium is excreted daily: half in urine and half in faeces. To maintain calcium balance, the same amount has to be absorbed in the small intestine from the diet. Because normally only 1/3rd of ingested calcium is absorbed, the dietary allowance for calcium is 0.8–1.5 g per day. However, calcium deficiency and low dietary calcium increases fractional calcium absorption.


Thiazide diuretics impede calcium excretion by facilitating tubular reabsorption.




1. Calcium chloride (27% Ca): is freely water soluble but highly irritating—tissue necrosis occurs if it is injected i.m. or extravasation takes place during i.v. injection. Orally also the solution irritates.


2. Calcium gluconate (9% Ca): is available as 0.5 g and 1 g tablets and 10% injection (5 ml amp.) It is nonirritating to g.i.t. and the vascular endothelium—a sense of warmth is produced on i.v. injection: extravasation should be guarded. It is the preferred injectable salt.


3. Calcium lactate (13% Ca): is given orally, nonirritating and well tolerated.


4. Calcium dibasic phosphate (23% Ca): is insoluble, reacts with HCl to form soluble chloride in the stomaCh. No. It is bland; used orally as antacid and to supplement calcium. 

5. Calcium carbonate (40% Ca): insoluble, tasteless and nonirritating. It has been used as an antacid—reacts with HCl to form chloride which may be absorbed from the intestines.


Side Effects


Calcium supplements are usually well tolerated; only g.i. side effects like constipation, bloating and excess gas (especially with cal. carbonate) have been reported.


Some Combined Formulations


CALCINOLRB: Cal. carb 0.375 g, Cal. Phos 75 mg + vit D3 250 IU tab.


CALCIUMSANDOZ: Cal. glucobionate 137.5 mg/ml inj. 10 ml amp., also tabs containing cal. carbonate 650 mg. KALZANA: Cal. dibasic phos 430 mg + Vit C and D3 200 IU tab, also syrup: Cal. gluconate 300 mg, Cal. lactobionate 1.1 g, Cal. phos. 75 mg per 5 ml, containing Vit A, C, niacinamide and D3 200 IU.


OSTOCALCIUM: Cal. phos 380 mg + Vit D3 400 IU tab, also syrup: Cal. phos 240 mg per 5 ml containing Vit D3 200 IU and B12.


SHELCAL: Cal. carb. 625 mg (eq 250 mg elemental cal), Vit D3 125 IU tab and per 5 ml syr.


MACALVIT: Cal. carb. 1.25 g, cholecalciferol 250 IU tab; Cal. gluconate 1.18 g, Cal. lactobionate 260 mg + Vit D3 100 IU per 5 ml syr.


CALCIMAX: Cal. carb. (150 mg cal), dibasic cal. phos. (23.3 mg cal) with magnesium, zinc and vit D3 200 IU tab.; also syrup cal. carb. (150 mg cal) with magnesium, zinc and vit D3 200 IU per 5 ml syrup.




1. Tetany


For immediate treatment of severe cases 10–20 ml of Cal. gluconate (elemental calcium 90–180 mg) is injected i.v. over 10 min, followed by slow i.v. infusion. A total of 0.450.9 g calcium (50 to 100 ml of cal. gluconate solution) over 6 hours is needed for completely reversing the muscle spasms. Supportive treatment with i.v. fluids and oxygen inhalation may be required. Long-term oral treatment to provide 1–1.5 g of calcium daily is instituted along with vit. D. Milder cases need oral therapy only.


2. As Dietary Supplement


Especially in growing children, pregnant, lactating and menopausal women. The dietary allowance recommended by National Institute of Health (1994) is—



Calcium supplement can reduce bone loss in predisposed women as well as men. It is often given to fracture patients, but if diet is adequate this does not accelerate healing.


3. Osteoporosis


In the prevention and treatment of osteoporosis with HRT/raloxifene/ alendronate, it is important to ensure that calcium deficiency does not occur. Calcium + vit D3 have adjuvant role to HRT/raloxifene/bisphosphonates in prevention and treatment of osteoporosis.


However, the efficacy of calcium ± vit D supplements alone in increasing bone mass or preventing fractures among menopausal women/elderly men is controversial. While several studies have reported a reduction in fracture risk, others have found no benefit. In the recently concluded 7 year prospective WHI study involving >36000 postmenopausal women (5179 years), the overall risk of fractures was the same in the calcium (1 g/day) + vit D (400 IU/ day) group as in the placebo group, though the bone mineral density at the hip was 1% higher in the treated group. Certain subgroups of osteoporotic subjects may benefit from calcium supplements, but the benefit appears to be marginal and limited to cortical bone loss only.


4. Empirically, Cal. gluconate i.v. has been used in dermatoses, paresthesias, weakness and other vague complaints. Any benefit is probably psychological due to warmth and other subjective effects produced by the injection.


5. As antacid (see Ch. No. 46).


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