Hypercalcemia medical therapy: Difference between revisions

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==Overview==
==Overview==
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==Medical Therapy==
==Medical Therapy==
===Pharmacotherapy===
===Pharmacotherapy===
The goal of therapy is to treat the hypercalcemia first and subsequently effort is directed to treat the underlying  cause.  
The goal of therapy is to treat the hypercalcemia first and subsequently effort is directed to treat the underlying  cause.<ref name="pmid1532633">{{cite journal| author=Bilezikian JP| title=Management of acute hypercalcemia. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 18 | pages= 1196-203 | pmid=1532633 | doi=10.1056/NEJM199204303261806 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1532633  }}</ref>
====Initial Therapy: Fluids and Diuretics====
====Initial Therapy: Fluids and Diuretics====
*hydration, increasing salt intake, and [[forced diuresis]].
*Hydration, increasing salt intake, and [[forced diuresis]]<ref name="pmid7342172">{{cite journal| author=Hosking DJ, Cowley A, Bucknall CA| title=Rehydration in the treatment of severe hypercalcaemia. | journal=Q J Med | year= 1981 | volume= 50 | issue= 200 | pages= 473-81 | pmid=7342172 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7342172  }}</ref>
**hydration is needed because many patients are dehydrated due to vomiting or renal defects in concentrating urine.
**Hydration is needed because many patients are dehydrated due to vomiting or renal defects in concentrating urine.
**increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary calcium excretion (In other words, calcium and sodium (salt) are handled in a similar way by the kidney. Anything that causes increased sodium (salt) excretion by the kidney will, ''en passant'', cause increased calcium excretion by the kidney)
**Increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary calcium excretion (In other words, calcium and sodium (salt) are handled in a similar way by the kidney. Anything that causes increased sodium (salt) excretion by the kidney will, ''en passant'', cause increased calcium excretion by the kidney)
**after rehydration, a [[loop diuretic]] such as [[furosemide]] can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and thence [[pulmonary edema]]. In addition, [[loop diuretics]] tend to depress renal calcium reabsorption thereby helping to lower blood calcium levels
**After rehydration, a [[loop diuretic]] such as [[furosemide]] can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and thence [[pulmonary edema]]. In addition, [[loop diuretics]] tend to depress renal calcium reabsorption thereby helping to lower blood calcium levels.
**can usually decrease serum calcium by 1-3 mg/dL within 24 h
**Can usually decrease serum calcium by 1-3 mg/dL within 24 h.
**caution must be taken to prevent potassium or magnesium depletion
**Caution must be taken to prevent potassium or magnesium depletion.


====Additional Therapy: Bisphosphonates and Calcitonin====
====Additional Therapy: Bisphosphonates and Calcitonin====
*[[bisphosphonates]] are [[pyrophosphate]] analogues with high affinity for bone, especially areas of high bone-turnover.  
*[[Bisphosphonates]] are [[pyrophosphate]] analogues with high affinity for bone, especially areas of high bone-turnover.  
**they are taken up by [[osteoclast]]s and inhibit osteoclastic bone resorption
**They are taken up by [[osteoclast]]s and inhibit osteoclastic bone resorption
**current available drugs include (in order of potency): (1st gen) [[etidronate]], (2nd gen) [[tiludronate]], IV [[pamidronate]], [[alendronate]], [[risedronate]], and (3rd gen) zolendronate
**Current available drugs include (in order of potency): (1st gen) [[etidronate]], (2nd gen) [[tiludronate]], IV [[pamidronate]], [[alendronate]], [[risedronate]], and (3rd gen) zolendronate
**all patients with cancer-associated hypercalcemia should receive treatment with [[bisphosphonates]] since the 'first line' therapy (above) cannot be continued indefinitely nor is it without risk. Further, even if the 'first line' therapy has been effective, it is a virtual certainty that the hypercalcemia will recur in the patient with hypercalcemia of malignancy. Use of bisphoponates in such circumstances, then, becomes both therapeutic and preventative
**All patients with cancer-associated hypercalcemia should receive treatment with [[bisphosphonates]] since the 'first line' therapy (above) cannot be continued indefinitely nor is it without risk. Further, even if the 'first line' therapy has been effective, it is a virtual certainty that the hypercalcemia will recur in the patient with hypercalcemia of malignancy. Use of bisphoponates in such circumstances, then, becomes both therapeutic and preventative.
**patients in [[renal failure]] and [[hypercalcemia]] should have a risk-benefit analysis before being given [[bisphosphonates]], since they are relatively contraindicated in [[renal failure]].
**Patients in [[renal failure]] and [[hypercalcemia]] should have a risk-benefit analysis before being given [[bisphosphonates]], since they are relatively contraindicated in [[renal failure]].


*[[Calcitonin]] blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption
*[[Calcitonin]] blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption.
**Usually used in life-threatening hypercalcemia along with rehydration, diuresis, and bisphosphonates
**Usually used in life-threatening hypercalcemia along with rehydration, diuresis, and bisphosphonates.
**Helps prevent recurrence of hypercalcemia
**Helps prevent recurrence of hypercalcemia.
**Dose is 4 Units per kg via subcutaneous or intramuscular route every 12 hours, usually not continued indefinitely
**Dose is 4 Units per kg via subcutaneous or intramuscular route every 12 hours, usually not continued indefinitely.


====Other Therapies====
====Other Therapies====
*rarely used, or used in special circumstances
*Other thearapies are rarely used, or used in special circumstances.
**[[plicamycin]] inhibits bone resorption (rarely used)
**[[Plicamycin]] inhibits bone resorption (rarely used)
**[[gallium]] [[nitrate]] inhibits bone resorption and changes structure of bone crystals (rarely used)
**[[Gallium]] [[nitrate]] inhibits bone resorption and changes structure of bone crystals (rarely used)
**[[glucocorticoids]] increase urinary calcium excretion and decrease intestinal calcium absorption
**[[Glucocorticoids]] increase urinary calcium excretion and decrease intestinal calcium absorption
***no effect in calcium level in normal or 1' hyperparathyroidism
***No effect in calcium level in primary hyperparathyroidism.
***effective in hypercalcemia due to osteolytic malignancies ([[multiple myeloma]], [[leukemia]], [[Hodgkin's lymphoma]], [[breast cancer|carcinoma of the breast]]) due to antitumor properties
***Effective in hypercalcemia due to osteolytic malignancies ([[multiple myeloma]], [[leukemia]], [[Hodgkin's lymphoma]], [[breast cancer|carcinoma of the breast]]) due to antitumor properties.
***also effective in [[hypervitaminosis D]] and [[sarcoidosis]]
***Also effective in [[hypervitaminosis D]] and [[sarcoidosis]].
**[[dialysis]] usually used in severe hypercalcemia complicated by [[renal failure]]. Supplemental phosphate should be monitored and added if necessary
**[[Dialysis]] usually used in severe hypercalcemia complicated by [[renal failure]]. Supplemental phosphate should be monitored and added if necessary.
**[[phosphate]] therapy can correct the hypophosphatemia in the face of hypercalcemia and lower serum calcium
**[[Phosphate]] therapy can correct the hypophosphatemia in the face of hypercalcemia and lower serum calcium.


====Contraindicated medications====
====Contraindicated medications====

Latest revision as of 19:26, 5 July 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Medical Therapy

Pharmacotherapy

The goal of therapy is to treat the hypercalcemia first and subsequently effort is directed to treat the underlying cause.[1]

Initial Therapy: Fluids and Diuretics

  • Hydration, increasing salt intake, and forced diuresis[2]
    • Hydration is needed because many patients are dehydrated due to vomiting or renal defects in concentrating urine.
    • Increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary calcium excretion (In other words, calcium and sodium (salt) are handled in a similar way by the kidney. Anything that causes increased sodium (salt) excretion by the kidney will, en passant, cause increased calcium excretion by the kidney)
    • After rehydration, a loop diuretic such as furosemide can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and thence pulmonary edema. In addition, loop diuretics tend to depress renal calcium reabsorption thereby helping to lower blood calcium levels.
    • Can usually decrease serum calcium by 1-3 mg/dL within 24 h.
    • Caution must be taken to prevent potassium or magnesium depletion.

Additional Therapy: Bisphosphonates and Calcitonin

  • Bisphosphonates are pyrophosphate analogues with high affinity for bone, especially areas of high bone-turnover.
    • They are taken up by osteoclasts and inhibit osteoclastic bone resorption
    • Current available drugs include (in order of potency): (1st gen) etidronate, (2nd gen) tiludronate, IV pamidronate, alendronate, risedronate, and (3rd gen) zolendronate
    • All patients with cancer-associated hypercalcemia should receive treatment with bisphosphonates since the 'first line' therapy (above) cannot be continued indefinitely nor is it without risk. Further, even if the 'first line' therapy has been effective, it is a virtual certainty that the hypercalcemia will recur in the patient with hypercalcemia of malignancy. Use of bisphoponates in such circumstances, then, becomes both therapeutic and preventative.
    • Patients in renal failure and hypercalcemia should have a risk-benefit analysis before being given bisphosphonates, since they are relatively contraindicated in renal failure.
  • Calcitonin blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption.
    • Usually used in life-threatening hypercalcemia along with rehydration, diuresis, and bisphosphonates.
    • Helps prevent recurrence of hypercalcemia.
    • Dose is 4 Units per kg via subcutaneous or intramuscular route every 12 hours, usually not continued indefinitely.

Other Therapies

  • Other thearapies are rarely used, or used in special circumstances.

Contraindicated medications

Hypercalcemia is considered an absolute contraindication to the use of the following medications:

References

  1. Bilezikian JP (1992). "Management of acute hypercalcemia". N Engl J Med. 326 (18): 1196–203. doi:10.1056/NEJM199204303261806. PMID 1532633.
  2. Hosking DJ, Cowley A, Bucknall CA (1981). "Rehydration in the treatment of severe hypercalcaemia". Q J Med. 50 (200): 473–81. PMID 7342172.

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