1. Calcium Mohammed Almeziny BsPharm R,Ph. Msc PhD Consultant clinical pharmacist

3. Corrected Calcium Equation n Corrected calcium mmol/L= serum calcium mmol/L+ 0.02 (40 - serum albumin g/L) n Corrected calcium mg/dl = serum calcium mg/dl + 0.8 (4 - serum albumin g/dL)

4. Functions n It regulates the secretary activities of –Exocrine glands –Endocrine glands n Cofactor –Enzyme systems –Coagulation cascade. n An essential component of bone metabolism. n Muscle contractility

5. 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.

6. Calcium Regulation

7. Calcium Regulation cont’d

8. How PTH Protects against Hypocalcemia? – Tubular reabsorption of Ca 2+. – Ca ++ and PO 4 release from osteoclastic bone resorption. – Intestinal absorption of Ca 2+. – Synthesis of 1-25DHCC (active Vit. D). – Excretion of phosphate.

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

10. Vitamin D Analogue Product Availability Calcitriol (1, 25 (OH) 2 D 3 ) Rocaltrol  Capsules 0.25 mcg 0.5 mcg Chole-calciferol (not used in renal) Vi-De 3  Alfacalcidol (1-alfa hydroxy- vitamin D 3) (Hydroxy-cholecalciferol) One-Alfa  Capsules 1 mcg and 0.25mcg Drops: 2 mcg/ml 1drop = 0.1mcg Injection: 1 mcg/0.5 ml ampule

11. Hypercalcemia etiology n Malignancy n Primary Hyperparathyroidism n Other conditions –Post-kidney transplantation, –Immobilization, –Hyperthyroidism, –Addison's disease,

12. Hypercalcemia etiology cont’d n Drugs –Vitamin A intoxication, –Vitamin D intoxication, –Thiazide diuretics, – Lithium, –Estrogens, –Tamoxifen, –Excessive calcium

13. Clinical Manifestations n The severity of the symptoms correlates well with free calcium concentrations. –Neurologic. –Cardiovascular. –Renal. –GI. –Musculoskeletal systems.

14. Therapeutic approaches n Increasing urinary excretion. n Inhibiting release of calcium from bone. n Reducing intestinal calcium absorption, n Enhancing calcium complex formation with chelating agents.

15. Therapeutic approaches cont’d n The underlying disease should also be treated if possible. n The specific treatment used depends on: – The serum ionized calcium conc. –The presenting signs and symptoms. –The severity and duration of hypercalcemia.

16. Pharmacological treatment

17. Hydration and Diuresis n Hydration and forced diuresis with furosemide generally are the first steps in the acute treatment of hypercalcemia. n Depresses Ca ++ reabsorption in tubules. n Lowers [Ca + + ] within 24 hrs. n Treatment of choice in patients without CHF or renal failure

18. Calcitonin n Used when saline hydration and furosemide diuresis fail to lower serum calcium concentration adequately or when their use is contraindicated. n Provides a rapid onset of hypocalcemic effect, but its duration of action is relatively short. n Reduces calcium conc.by inhibiting osteoclastic bone resorption.

19. Calcitonin cont’d n It may also increase the renal excretion of calcium and phosphorus. n The serum calcium conc. is often reduced several hours after it is administered, and the response may last approximately 6 to 8 hours. n After long-term therapy, antibodies may develop.

20. The bisphosphonates n could be used to elicit a longer hypocalcemic response. n They induce apoptosis of osteoclasts as well as certain tumor cells. n Onset 48 hrs, Duration >10 days

21. The bisphosphonates cont’d n Etidronate, n Pamidronate n Zoledronic acid ( Preferred biphosphonate for hypercalcemia of malignancy).

22. Gallium nitrate n Inhibits bone resorption. n Patients should be well hydrated during therapy. n A urine output of ~2 L/day should be maintained owing to risk for nephrotoxicity (10%). n It is effective in the treatment of cancer- related hypercalcemia when compared with agents such as calcitonin and bisphosphonates.

23. Phosphate n Inhibits bone resorption; soft tissue calcification. n IV onset 24 hrs, but not drug of choice. n Oral agents used for chronic therapy. n Contraindicated in renal failure

24. Hypocalcemia

25. Hypocalcemia etiology PTH deficiency acquired Thyroidectomy Parathyroidectomy Hypomagnesemia Irradiation Infiltrative Developmental defect of parathyroid glands

26. Hypocalcemia etiology cont’d Vitamin D Deficiency Nutritional deficiency and lack of skin exposure Osteomalacia Adult Proximal muscle weakness Rickets Type 1 Hereditary vitamin D deficiency due to lack of 1-alpha hydroxylase Renal insufficiency

27. 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

28. Clinical Manifestations n Tendon reflexes are hyperactive n Life threatening complications –Laryngospasm –Cardiac arrhythmias n ECG changes

29. Clinical Manifestations cont’d Latent tetany n Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic) n Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)

30. Treatment of Hypocalcemia Calcium PO vs IV Vitamin D 25 and/or 1,25 (OH) Vitamin D

31. Treatment of Hypocalcemia cont’d n Hypocalcemia: I.V.: n 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 n Moderate-to-severe (without seizure or tetany; ionized calcium [<1 mmol/L]): 4000 mg (9.3 mmol) over 4 hours

32. Treatment of Hypocalcemia cont’d n Hypocalcemia: I.V.: n Severe symptomatic (eg, seizure, tetany): 1000-2000 mg (2.325-4.65 mmol) over 10 minutes; repeat every 60 minutes until symptoms resolve.

33. Treatment of Hypocalcemia cont’d n Hypocalcemia: I.V.: n Continuous infusion: 5-20 mg/kg/hour

34. Treatment of Hypocalcemia cont’d n Repeat ionized calcium measurement 6-10 hours after completion of administration. n Check for hypomagnesemia and correct if present. n Consider continuous infusion if hypocalcemia is likely to recur due to ongoing losses

35. Administration: I.V. n 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.

36. Administration: I.V. cont’d n Not for I.M. administration; not for routine SubQ administration (exception: treatment of hydrofluoric acid burns [unlabeled route/use]).

37. 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.

38. Questions?