Bone Anabolic agents

BO N E AN AB O L I C A G E N T S

C A L C I U M S A L T A G E NT S

CALCIUM GLUCONATE AND CALCIUM LACTATE

• oral calcium replacements

CALCIUM CARBONATE

• chewable tablets

M E C H A N I S M O F A C T I O N

• Calcium Gluconate is the gluconate salt of calcium and is essential for normal nerve, muscle, and cardiac function as well as to prevent bone loss and maintain calcium balance. • Bone calcium is in constant exchange with plasma calcium so disturbances in the calcium balance may deplete body stores. Therefore, calcium salt agents such as these promote restoration of calcium balance. • Administration of calcium gluconate is the first step in the emergency management of hyperkalaemia: o The resting membrane potential (RMP) becomes less negative in hyperkalaemia, bringing it closer to the threshold potential (TP). o This means that the cardiac myocyte requires less of a stimulus to create an action potential. o Calcium gluconate prevents this by increasing the threshold potential. o As a result, the gap between RMP and TP is restored. This stabilises and protects the cardiac membrane, preventing the development of potentially fatal arrhythmias.

• Calcium lactate salt consists of two lactate anions for each calcium cation and is commercially prepared by neutralising lactic acid with calcium carbonate or calcium hydroxide. • In aqueous environments such as in the gastrointestinal (GI) tract, calcium lactate dissociates into calcium cation and lactic acid anions which are the conjugate base of lactic acid that is a ubiquitous intermediate in metabolic pathways such as gluconeogenesis. • Calcium must be in its freely soluble form in order to be absorbed or bound to a soluble organic molecule and absorption mainly occurs at the duodenum and proximal jejunum due to the more acidic pH and abundance of the calcium binding proteins. • Mean calcium absorption in the small intestine is about 25% of calcium intake and is mediated by both passive diffusion and active transport.

• Calcium carbonate is an inorganic salt that is basic and acts by neutralizing hydrochloric acid in gastric secretions. This neutralization results in the formation of calcium chloride, carbon dioxide and water.

Around 90% of calcium chloride is converted to insoluble calcium salts such as calcium phosphate and calcium carbonate. • The calcium is quickly taken up by skeletal tissues following absorption and distribution into extracellular fluids and can also act as a co-factor to several enzymes. • Due to their poor absorption, they can act as antacids within the stomach to minimize gastric reflux disorders.

I N D I C A TI O N S

• Calcium deficiency • Hypoparathyroidism • Supplement osteoporosis • Calcium recommended daily intake > 1200mg daily

C O N T R A I N D I C A TI O N S

• Conditions associated with hypercalcaemia or elevated vitamin D levels for example sarcoidosis • History or active renal calculi

Refer to Calcium Homeostasis lecture for more information

V I T A M I N D S U P P L E M E NT S : E R G O C A L C I F E R O L D 2

M E C H A N I S M O F A C T I I O N

• Fat soluble vitamin that is considered a hormone • Cholecalciferol (vitamin D3) is synthesized in the skin from precursor 7-dehydrocholesterol and is stimulated by UV light • Ergocalciferol (vitamin D2) is derived from plants and is added to food preparations commercially • vitamin D is metabolized in the liver via a hydroxylation reaction into a hydroxycholecalciferol • A second hydroxylation reaction occurs in the proximal renal tubular cells to activate the metabolite

Calcitriol • Calcitriol, (active vitamin D) signals through nuclear receptors and increases calcium absorption by increasing receptor expression in the intestinal mucosa • vitamin D is stored in fat tissue therefore a single large dose may be effective for several weeks

I N D I C A TI O N S

• Hyperparathyroidism • Renal and liver disease • Dietary deficiency • lack of sunlight • osteoporosis

Refer to Calcium Homeostasis lecture for more information

P A R A T H Y R O I D H O R M O NE P E P T I D E : T E R I P E P T ID E

M E C H A N I S M O F A C T I O N

• stimulate bone formation by increasing the number and action of osteoblasts