Calcium + Phosphate disorders

Hypocalcemia

Total serum < 8.6

Ionized < 1.12

What causes Hypocalcemia

Vit D deficiency, hungry bone syndrome, hypo magnesia

What drugs cause hypocalcemia

Diuretics(loop)

Calcitonin

Biphosphonate

Cinacalcet

Rec dietary allowance of Ca for 19-50 year olds

M: 1000 mg

F: 1000 mg

Rec dietary allowance of Ca for 51-70 year olds

M: 1000 mg

F: 1200 mg

Rec dietary allowance of Ca for 71+ year olds

M:1200 mg

F:1200 mg

What is used for mild asymptomatic and chronic hypocalcemia

Calcium oral replacement

Carbonate → most elemental → requires stomach acid

Acetate → CKD phosphate binder

Citrate → better absorption if on PPI or achlorhydria

IV calcium replacement: Mild-mod asymptomatic TC: 7-8.5, IC: 1-1.12

1-2 gm Calcium gluconate

IV calcium replacement: Severe asymptomatic TC: <7, IC: < 1

up to 3 gm, 1g/1hr Calcium gluconate

IV calcium replacement: Symptomatic or severe TC: <7, IC: < 1

1-2 g calcium gluconate over 10 mins; repeat until symptoms resolve, then infuse

calcium DDI

Tetracycline (Doxycycline) → give 2 hrs before or 4 hrs after Ca

Fluoroquinolones (cipro, levofloxacin) → separate dose to avoid chelation

Bisphosphonates → alendronate → take on empty stomach; avoid calcium within 30-60 mins 

Thyroid hormones (levothyroxine) → separate by at least 4 hrs

Iron supplements → separate dose by 2 hrs 

Hypercalcemia levels

Total > 10.2

Ionized > 1.3

Path of hypercalcemia

1. Cancer(malignancy)

2. Primary hyperparathyroidism

3. Drug induced

Which drug cause Hypercalcemia

Thiazides

Lithium

Vit A

Calcium

Hypercalcemia: mild to moderate

10.2 - 13 → asymptomatic

probably from drugs and primary hyperparathyroidism

Hypercalcemia: severe Acute

>13 mg/dL

anorexia, N/V, constipation, polyuria, polydipsia, nocturne

malignancy

Hypercalcemia: severe chronic

>13

nephrolithiasis, metastatic calcification, hypercalciuria, renal insufficiency, QT shortening

Primary hyperparathyroidism

HyperCa2+ crisis

>15

Obtundantion (unarousable), renal failure, coma, life-threatening arrhythmias, T-wave widening

could be anything

Acute Hypercalcemia treatment

1. Calcitonin 4 IU/kg Sc/IM

2. Normal saline 1-2 bolus, then 250-300 mL/h

3. Zoledronic acid 4 mg IV

4. Hemodialysis

Asymptomatic Hypercalcemia treatment >12

1. Saline rehydration 1-2 L then 250 mL/hr

2. loop diuretic: Furosemide 40-80 mg IV 1-4 h

3. Calcitonin 4-8 IU/kg q12h

4. Glucocorticoid 40-60 oral prednisone

5. IV bisphophonate or denosumab (malignancy)

Symptomatic Hypercalcemia treatment: non life threatening

1. Saline rehydration 1-2 L then 250 mL/hr

2. loop diuretic: Furosemide 40-80 mg IV 1-4 h

3. Calcitonin 4-8 IU/kg q12h

4. Glucocorticoid 40-60 oral prednisone

5. IV bisphophonate or denosumab (malignancy)

Symptomatic Hypercalcemia treatment: life threatening functional kidneys

1. Saline rehydration 1-2 L then 250 mL/hr

2. loop diuretic: Furosemide 40-80 mg IV 1-4 h

3. Calcitonin 4-8 IU/kg q12h

4. Glucocorticoid 40-60 oral prednisone

5. IV bisphophonate or denosumab (malignancy)

6. Hemodialysis if refractory

Symptomatic Hypercalcemia treatment: life threatening severe renal insufficiency

1. hemodialysis

2. calcitonin

3. glucocorticoid

Calcitonin (Hypercalemia)

Alt for saline hydration C/I → severe HF, moderate or severe HCM bridge w/ bisphosphonate or denosumab

Allergy to salmon

Calcitonin MOA

inhibits bone resorption, promotes calciuresis via dcr renal tubular reabsorption 

Onset: within few hours

Maximal effect within 24-48 hours, tachyphylaxis caused by antibody formation

Biphosphonates IV

First line for hypercalcemia of malignancy

ADE: fever, fatigue, skeletal pain, renal impairment, osteonecrosis of jaw

Biphosphonates IV: Pamidronate (Aredia)

60-90 mg IV over 2-24 hrs x 1st dose → may repeat after > 7 days

Biphosphonates IV: Zoledronic Acid (Zometa)

4 mg IV over > 15 mins x 1 dose → may repeat after > 7 days

Denosumab (Xgeva)

Prefered if refractory or recurrent after IV bisphonate → alt first line for HCM + malignancy

Dose: 120 mg subq every 4 weeks + 120 on days 8 and 15th of the first month

Option in renal impairment

Hypophosphatemia: moderate

1.5 to 2.2

Hypophosphatemia: Severe

<1.5

Neurologic symptoms: encephalopathy, delirium, seizures, coma

Path of hypophosphatemia

phosphate binders + low dietary phosphorus

Hyperparathyroidism, Vit D deficiency, incr FGF23 + medications

Extracellular to intracellular redistribution → refeeding syndrom, hungry bone sydrome, medications, DKA treatment

Path of hypophosphatemia: medications

Dcr tubular reabsorption → diuretics, acetazolamide, ferric carboxymaltose

Extra to intra cellular redistribution → dextrose, insulin, glucagon, catecholamines, calcitonin

Asymptomatic, mild mod hypophosphatia treatment

1-2 g/day in 3-4 divided doses

Goal correct within 7-10 days

all phosphate same

Oral phosphate replacement: Phos-NaK

neutral 7 for both mEq/packet

Oral phosphate replacement: Phospha250 neutral/ K-Phos Neutral

A lot more sodium 1.1 K - 13 Na

Oral phosphate replacement: K-Phos No. 2

2.3 K to 5.8 Na

IV phosphorus: Symptomatic or severe hypophosphatemia

Infuse < 7.5 mol/hr bc risk of thrombophlebitis

15 mmol - mild, 30 mmol - mod, 45 mmol severe

IV phosphorus: Sodium phosphate

if K > 3.5

IV phosphorus: Potassium phosphate

if K < 3.5

Hypophosphatemia: Mild

2.3-2.7