A Textbook of Clinical Pharmacology and Therapeutics

298 CALCIUM METABOLISM
Diet Ultraviolet light on skin
Low plasma
calcium and
high phosphate
Vitamins D 2 and D 3
(inactive)
PTH
Liver
Vitamins D 3
(inactive)
25-hydroxycholecalciferol
(major circulating metabolite but inactive)
(�)
1,25-dihydroxycholecalciferol
(1,25-DHCC) – powerfully
active hormone
Kidney
Normal plasma calcium
and phosphate
1. Calcium and ergocalciferol tablets provide a
physiological dose of vitamin D. They are used in the
prophylaxis of rickets and osteomalacia. The small dose of
calcium is unnecessary, but a preparation of vitamin D
alone is not available.
2. Calciferol tablets provide a pharmacological dose of
vitamin D and are used for treatment of hypoparathyroidism
and in cases of vitamin D-resistant
rickets due to intestinal malabsorption or chronic liver
disease.
3. α-Calcidol rapidly undergoes hydroxylation to 1,25-
DHCC. It is used in:
• renal rickets, together with a phosphate-binding
agent;
• hypoparathyroidism and (paradoxically) secondary
hyperparathyroidism;
• vitamin D-resistant rickets;
• nutritional and malabsorptive rickets can be treated
with small doses of α-calcidol instead of conventional
vitamin D.
4. Calcitriol (1,25-DHCC) is also available for the treatment
of vitamin D-resistant rickets and is the treatment of
choice for pseudohypoparathyroidism (an uncommon
metabolic disorder where low plasma calcium is caused
by resistance to the biochemical action of PTH).
Adverse effects
Hypercalcaemia, which can accelerate renal dysfunction, is the
main problem. Regular plasma calcium and creatinine measurements
(weekly initially) are essential.
7-dehydrocholesterol
24,25-dihydroxycholecalciferol –
weak activity
CALCIUM
Figure 39.1: Metabolic pathway of vitamin D.
PTH, parathormone.
Calcium salts (lactate or gluconate) are used in conjunction
with calciferol in the treatment of rickets and osteomalacia, and
in hypocalcaemic tetany. Calcium chloride (i.v.) is uniquely
Key points
Vitamin D and calcium metabolism
• Plasma calcium concentrations are tightly controlled by
the balance of hypocalcaemic effects of calcitonin and
hypercalcaemic effects of PTH and vitamin D and Ca 2�
intake.
• Vitamin D is available in a number of forms, many of
which are derived from each other by sequential
metabolism in the skin, liver and kidney, and each of
which has specific indications.
• The most potent and rapid-acting orally available
vitamin D preparations are 1,25 dihydroxycholecalciferol,
and 1-α-hydroxycholecalciferol. They
are used in renal rickets or vitamin D-resistant rickets.
• When patients are hypocalcaemic, calcium can be
supplemented orally as calcium carbonate with or
without various preparations of vitamin D. If urgent
calcium replacement is required, a 10% solution of
calcium lactate or gluconate (the former yielding
more calcium) may be administered intravenously.
• Patients who are receiving vitamin D plus calcium
should have periodic checks of their serum Ca 2� and
creatinine concentrations, as the major adverse effect is
hypercalcaemia.