Calcium

Mohammed Almeziny BsPharm R,Ph. Msc PhD

Consultant clinical pharmacist

Corrected Calcium Equation

Corrected calcium mmol/L=

serum calcium mmol/L+ 0.02 (40 - serum albumin g/L)

Corrected calcium mg/dl =

serum calcium mg/dl + 0.8 (4 - serum albumin g/dL)

Functions It regulates the secretary activities of

– Exocrine glands – Endocrine glands

Cofactor – Enzyme systems – Coagulation cascade.

An essential component of bone metabolism.

Muscle contractility

osteoclasts

osteoblasts

An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone. This process is known as bone resorption.

Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are sophisticated fibroblasts that express all genes that fibroblasts express, with the addition of the genes for bone sialoprotein and osteocalcin.

Calcium Regulation

Calcium Regulation cont’d

How PTH Protects against Hypocalcemia?

– Tubular reabsorption of Ca2+ .

– Ca++ and PO4 release from osteoclastic bone resorption.– Intestinal absorption of Ca2+ .

– Synthesis of 1-25DHCC (active Vit. D).– Excretion of phosphate.

The UV wavelength of 290-315 nm does not penetrate the windows glass

The UV wavelength of 290-315 nm

Vitamin D Analogue

Vitamin D Analogue Product Availability

Calcitriol(1, 25 (OH)2D3)

Rocaltrol Capsules 0.25 mcg 0.5 mcg

Chole-calciferol (not used in renal)

Vi-De 3

Alfacalcidol (1-alfa hydroxy- vitamin D3)

(Hydroxy-cholecalciferol)

One-Alfa Capsules1 mcg and 0.25mcgDrops: 2 mcg/ml1drop = 0.1mcgInjection: 1 mcg/0.5 ml ampule

Hypercalcemia etiology

Malignancy Primary Hyperparathyroidism Other conditions

– Post-kidney transplantation, – Immobilization, – Hyperthyroidism, – Addison's disease,

Hypercalcemia etiology cont’d

Drugs – Vitamin A intoxication, – Vitamin D intoxication, – Thiazide diuretics,– Lithium, – Estrogens, – Tamoxifen, – Excessive calcium

Clinical Manifestations The severity of the symptoms correlates

well with free calcium concentrations.– Neurologic.– Cardiovascular. – Renal.– GI.– Musculoskeletal systems.

Therapeutic approaches Increasing urinary excretion. Inhibiting release of calcium from bone. Reducing intestinal calcium absorption, Enhancing calcium complex formation

with chelating agents.

Therapeutic approaches cont’d

The underlying disease should also be treated if possible.

The specific treatment used depends on:– The serum ionized calcium conc.– The presenting signs and symptoms.– The severity and duration of hypercalcemia.

Pharmacological treatment

Hydration and Diuresis Hydration and forced diuresis with

furosemide generally are the first steps in the acute treatment of hypercalcemia.

Depresses Ca++ reabsorption in tubules. Lowers [Ca+ +] within 24 hrs. Treatment of choice in patients without

CHF or renal failure

Calcitonin

Used when saline hydration and furosemide diuresis fail to lower serum calcium concentration adequately or when their use is contraindicated.

Provides a rapid onset of hypocalcemic effect, but its duration of action is relatively short.

Reduces calcium conc.by inhibiting osteoclastic bone resorption.

Calcitonin cont’d

It may also increase the renal excretion of calcium and phosphorus.

The serum calcium conc. is often reduced several hours after it is administered, and the response may last approximately 6 to 8 hours.

After long-term therapy, antibodies may develop.

The bisphosphonates

could be used to elicit a longer hypocalcemic response.

They induce apoptosis of osteoclasts as well as certain tumor cells.

Onset 48 hrs, Duration >10 days

The bisphosphonates cont’d

Etidronate, Pamidronate Zoledronic acid ( Preferred

biphosphonate for hypercalcemia of malignancy).

Gallium nitrate Inhibits bone resorption. Patients should be well hydrated during

therapy. A urine output of ~2 L/day should be

maintained owing to risk for nephrotoxicity (10%).

It is effective in the treatment of cancer-related hypercalcemia when compared with agents such as calcitonin and bisphosphonates.

Phosphate

Inhibits bone resorption; soft tissue calcification.

IV onset 24 hrs, but not drug of choice. Oral agents used for chronic therapy. Contraindicated in renal failure

Hypocalcemia

Hypocalcemia etiology PTH deficiency

acquiredThyroidectomyParathyroidectomyHypomagnesemiaIrradiationInfiltrative

Developmental defect of parathyroid glands

Hypocalcemia etiology cont’d

Vitamin D Deficiency

Nutritional deficiency and lack of skin exposureOsteomalacia

Adult Proximal muscle weakness

Rickets Type 1Hereditary vitamin D deficiency due to lack of 1-alpha

hydroxylase

Renal insufficiency

Hypocalcemia etiology cont’d

Calcium Deposition Extravascular Deposition

Hyperphosphatemia due to tumor lysis, rhabdo, renal failure

“Hungry bone syndrome” Intravascular deposition

Citrate in blood transfusion lactate

Clinical Manifestations Tendon reflexes are hyperactive Life threatening complications

– Laryngospasm– Cardiac arrhythmias

ECG changes

Clinical Manifestations cont’d

Latent tetany Trousseau sign of latent tetany

(eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)

Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)

Treatment of Hypocalcemia

CalciumPO vs IV

Vitamin D25 and/or 1,25 (OH) Vitamin D

Treatment of Hypocalcemia cont’d

Hypocalcemia: I.V.: Mild (ionized calcium: [1-1.2 mmol/L]):

1000-2000 mg (2.325-4.65 mmol) over 2 hours; asymptomatic patients may be given oral calcium

Moderate-to-severe (without seizure or tetany; ionized calcium [<1 mmol/L]): 4000 mg (9.3 mmol) over 4 hours

Treatment of Hypocalcemia cont’d

Hypocalcemia: I.V.: Severe symptomatic (eg, seizure,

tetany): 1000-2000 mg (2.325-4.65 mmol) over 10 minutes; repeat every 60 minutes until symptoms resolve.

Treatment of Hypocalcemia cont’d

Hypocalcemia: I.V.: Continuous infusion: 5-20 mg/kg/hour

Treatment of Hypocalcemia cont’d

Repeat ionized calcium measurement 6-10 hours after completion of administration.

Check for hypomagnesemia and correct if present.

Consider continuous infusion if hypocalcemia is likely to recur due to ongoing losses

Administration: I.V.

Administer slowly (~1.5 mL calcium gluconate 10% per minute; not to exceed 200 mg/minute except in emergency situations) through a small needle into a large vein in order to avoid too rapid increases in the serum calcium and extravasation.

Administration: I.V. cont’d

Not for I.M. administration; not for routine SubQ administration (exception: treatment of hydrofluoric acid burns [unlabeled route/use]).

Conversions:

Calcium Gluconate10%

1 gram (10ml) = 93 mg elemental

calcium = 4.65 mEq

= 2.325 mmol.

20mg of elemental calcium per mEq.

0.5 mmol of elemental calcium = 1.0 mEq.

Questions?