Pharm of Parathyroid and Bone Flashcards

1
Q

Calcium and Phosphate Ions

A

Important minerals for general cellular function as well as major constituents of bone. Plasma levels of calcium are regulated within narrow limits [8.8-10.4 mg/dl].

a. Intracellular Ca++ involved in muscular contraction, fusion and release of storage vesicles for hormones and neurotransmitters, and as critical 2nd messenger; in extracellular fluids, Ca++ promotes blood coagulation and supports formation and remodeling of skeleton.
b. Intracellular PO43- component of: phospholipids, phosphorylated nucleotides, glycolytic pathway intermediates, phosphate buffer systems
c. 98% of Ca++ and 85% of PO4— stored in bone
d. Plasma Ca++: Ionized (50%), protein-bound (46%), complexed with organic ions (4%)

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2
Q

Direct actions of Vit D, PTH

A

a. D stimulates the intestinal absorption of Ca and P
b. Both PTH and D promote bone formation and resorption by stimulating osteoblasts and osteoclasts
c. At the kidney, both D and PTH enhance reabsorption of Ca - D enhances P retention while PTH and FGF23 stimulate renal excretion of P

NET EFFECT on Serum Levels:
PTH: ↑ Ca and ↓ P D: ↑ Ca and ↑ P FGF23: ↓ P

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3
Q

Feedback loops include:

A
  • PTH stimulation of activation of D via the kidney
  • D and Ca++ inhibition of PTH synthesis and release from parathyroid glands
  • FGF23 inhibition of D activation in the kidney.
  • CT is less critical for calcium homeostasis but in pharmacologic concentrations can reduce serum Ca and P by inhibiting bone resorption.
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4
Q

Parathyroid Hormone

A

a. Structure / Pharmacokinetics. Single chain 84 AA; 1-34 fragment is biologically active [teriparatide]. Cleared from liver and kidneys with t1/2 of minutes.
b. Primary stimulus for synthesis and secretion is hypocalcemia (decreased PTH if hypercalcemia). Vitamin D interacts with receptor on parathyroid gland to decrease PTH release

c. In bone, PTH increases the number and activity of osteoclasts via actions on osteoblasts to induce a membrane-bound protein called RANK (receptor activator of nuclear factor B) ligand (RANKL).
i. This factor then acts on osteoclasts precursors and osteoclasts, increasing their number and activity, and increasing bone remodeling. This is a specific sequence of cellular events initiated by bone resorption and followed by osteoblastic bone formation.
ii. Net effect of excess PTH is to increase bone resorption, BUT low and intermittent doses of PTH stimulate formation without first increasing bone resorption

d. In kidney, PTH increases ability of nephron to reabsorb calcium, but reduces reabsorption of phosphate.
i. Also important action to stimulate renal production of active D3 [1,25(OH)2D3]

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5
Q

Vitamin D [1,25(OH)2D3]

Biosynthesis / Pharmacokinetics

A

. Dietary vitamin D requires metabolism to active form.

  1. 7-dehydrocholesterol is photoconverted via ultraviolet irradiation in skin to form Vitamin D3
  2. Vitamin D3 (dietary vitamin D) is converted to 25(OH) Vitamin D3 in liver
  3. 25(OH) Vitamin D3 is converted to 1,25(OH)2 Vitamin D3 in kidney (most potent agent)
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6
Q

Vitamin D Preparations for Repletion and Supplementation

A

a. Vitamin D3 - cholecalciferol (Delta-D): Preferred over vitamin D metabolites because of modest cost.
b. Vitamin D2 - ergocalciferol [from plant ergosterol]: Studies have shown that ergocalciferol is LESS efficient than D3 in elevating serum 25-OHD3, thus D3 should be used when possible.

25-Hydroxyvitamin D3 - calcifediol: Does not require hepatic 25-hydroxylation and is most *useful in patients with liver disease. Onset of action is more rapid and half-life is shorter than D3. Alfacalcidol only available in Canada.

c. 1,25-Dihydroxyvitamin D3 - calcitriol: Most useful in patients with decreased synthesis of calcitriol (chronic renal failure or type 1 vitamin D-dependent rickets).
i. Calcitriol has a rapid onset of action and a half-life of only 6 hours. Associated with hypercalcemia so patients should be followed closely.

d. Dihydrotachysterol: Functionally equivalent to 1α-OHD3, requires hepatic 25-hydroxylation to become therapeutically active.
i. *Alternative for use in disorders that calcitriol is used. Rapid onset of action and relatively short duration of action.

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7
Q

Vitamin D Pharmacodynamics

A

a. Synthesis of calcitriol (1,25-dihydroxyvitamin D3, most active form of vitamin D) in kidney is stimulated by PTH (released in response to hypocalcemia).
i. Hypophosphatemia also stimulates calcitriol synthesis directly

b. In intestine, calcitriol appears to act by induction of new protein synthesis (calcium binding-protein and TRPV6-intestinal calcium channel) and by modulating calcium flux across brush border
i. These actions result in enhanced absorption of calcium and phosphate
ii. This effect occurs at lower concentrations of vitamin D and is the basis for its use in the treatment of rickets (osteomalacia). The increase in serum concentrations of Ca++ and PO43- leads to increased bone mineralization.

c. In bone, calcitriol has effects similar to PTH.
i. Can induce RANK ligand in osteoblasts and proteins such as osteocalcin which may regulate the bone mineralization process
ii. This effect on RANKL occurs at higher concentrations of vitamin D that stimulate release of calcium from bone

d. In kidney, calcitriol decreases excretion of calcium and phosphate

e. In parathyroid gland, calcitriol decreases release of PTH, thus reducing its own synthesis (negative feedback)
i. Analogs of calcitriol are available for the treatment of secondary hyperparathyroidism
ii. They inhibit release of PTH, but will NOT cause hypercalcemia (NO increase in intestinal Ca++ absorption or bone Ca++ mobilization (Paracalcitol , Doxercalciferol)

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8
Q

Review of Parathyroid Hormone Actions

A

a. Parathyroid Gland
i. Hypocalcemia is major stimulus for release
ii. Vit D and increased Ca++ inhibit PTH release via distinct receptors

b. Sites of PTH action

1) Intestine
i. Increased Ca++ absorption via—> 1,25(OH)2 D3 synthesis

  1. Bone
    i. Activates OCs–> increase bone remodeling
    ii. Acute effect–> increase bone resorption—> Increased Ca++
  2. Kidney
    i. Increased reabsorption of Ca++ at DCT
    ii. Increased excretion of PO4
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9
Q

Review of Vitamin D Actions

A

a. Parathyroid Gland
i. Decreased release of PTH (via feedback inhibition of PTH synthesis)

b. Intestine *
i. Increased synthesis of Ca++-binding protein and channel
ii. Enhanced dietary absorption of Ca++ and PO4

c. Bone
i. Induce RANK ligand in OBs –> role in bone mineralization

d. Kidney
i. Decreased excretion of Ca++ and PO4

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10
Q

Vitamin D Preparations

Repletion and Maintenance

A

a. Vitamin D3 – cholecalciferol
i. Preferred over other vitamin D metabolites for repletion – modest cost

b. Vitamin D2 – ergocalciferol (from plants)
i. Less efficient in elevating 25-OHD levels than D3 in repletion states

c. 1,25-Dihydroxyvitamin D3 – calcitriol
i. Active form of Vitamin D - also as parenteral formulation
ii. Most useful in CKD and vitamin D-dependent rickets
iii. Rapid onset of action, half-life of 6 hours

d. 25-Hydroxyvitamin D3 – calcidiol (not readily available in US)
i. Does not require hepatic hydroxylation
ii. *Useful in patients with liver disease
iii. More rapid onset, shorter duration than D3

e. Dihydrotachysterol
i. Activated by hepatic 25-OH - equivalent to 1-OHD3 in function
ii. Can be used in disorders for which calcitriol is used

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11
Q

Vitamin D Preparations for Repletion and Supplementation

*handout

A

Vitamin D3 - cholecalciferol: Preferred over vitamin D metabolites because of modest cost.

Vitamin D2 - ergocalciferol: Studies have shown that ergocalciferol is **LESS efficient than D3 in elevating serum 25-OHD3, thus D3 should be used when possible.

25-Hydroxyvitamin D3 - calcifediol: Does not require hepatic 25-hydroxylation and is most **useful in patients with liver disease. Onset of action is more rapid and half-life is shorter than D3.
i. Used in liver disease

1,25-Dihydroxyvitamin D3 - calcitriol:
i. Most useful in patients with decreased synthesis of calcitriol (chronic renal failure or type 1 vitamin D-dependent rickets).

Dihydrotachysterol: Functionally equivalent to 1α-OHD3, requires hepatic 25-hydroxylation to become therapeutically active.
i. Alternative for use in disorders that calcitriol is used.

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12
Q

Primary HyperparathyroidismTreatment

A
  1. Surgery
    i. Adenoma - 1 Gland
    ii. Hyperplasia - 3 1/2 Glands
  2. Calcimimetic Drug (Cinacalcet)
  3. Anti-Resorptive Bone Drug
    i. Bisphosphonate, Denosumab
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13
Q

Calcimimetics- Uses

A

Cinacalcet

a. *Binds allosterically to calcium-sensing receptor (CaSR) in PT gland
b. Increases sensitivity of CaSR to Ca++—> reduced release of PTH (no hypercalcemia)
c. Complementary mechanism to Vit D and analogs that target the VDR
d. *Used in secondary hyperparathyroidism and non-surgical option in primary hyperparathyroidism

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14
Q

Vitamin D Analogs

Other Uses

A

Calcitriol Analogs – Paracalcitol

a. Inhibits PTH release from gland via action at D3 receptor (VDR) - *used in secondary hyperparathyroidism
b. Does NOT increase Ca++ absorption or mobilization from bone—> *NO hypercalcemia
c. Clinical advantage over calcitriol uncertain

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15
Q

Secondary Renal Osteodystrophy - CVPR

A

a. Pathophysiology: Failing kidney cannot excrete PO4 or synthesize D3— Increased PO4 levels and decreased in plasma Ca++ —> Increased PTH release—> Increased one turnover—> bone disease
b. Vitamin D and metabolites—> decreased PTH release indirectly (Increased GI Ca++ absorption –> hypercalcemia) and directly (decreased synthesis)
c. Paracalcitol—> acts selectively at D3 receptors on PT gland - not at intestine - so no hypercalcemia
d. Calcimimetics—> bind Ca++-sensing cells on PT gland - increased Ca++ —> reduced release of PTH (no hypercalcemia)
e. Phosphate binding agents—> bind PO4 in gut –> decreased absorption —> decreased plasma levels

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16
Q

Calcitonin Actions on Bone

A

a. Released from parafollicular cells of thyroid–> primary stimulus for calcitonin release is hypercalcemia
b. Action of Calcitonin

1) Bone*
i. Inhibits osteoclastic bone resorption

  1. Kidney
    i. Increases excretion of Ca++ and PO4

NOTE: No demonstrable problem in calcium homeostasis if deficiency (thyroidectomy) or excess (thyroid carcinoma)

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17
Q

Estrogen Actions on Bone

A

a. Positive effects on bone mass - agonist at ERα receptors on OBs-OCs
b. Estrogens directly regulate Osteoblasts—> increase differentiation - decrease apoptosis

c. *Major effect of estrogens–> decrease number and activity of OCs
i. lower osteoclast activity

d. Alters OB cytokines—> decrease stimulating signals [IL-6, TNF-α] and increase anti-resorptive BMP-2 and TGF-β

e. Estrogens increase OB production of osteoprotegerin (OPG)
i. OPG is “decoy” receptor–> binds RANK-L —> prevents OC activation

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18
Q

Apart from improving osteoblasts, how does estrogen help positive bone mass?

A

a. Estrogens directly regulate Osteoblasts—> increase differentiation - decrease apoptosis

b. Estrogens increase OB production of osteoprotegerin (OPG)
i. OPG is “decoy” receptor–> binds RANK-L —> prevents OC activation

19
Q

Glucocorticoid Actions on Bone

A

a. Glucocorticoids decrease bone density: involves multiple mechanisms
b. Lowering of serum Ca++ (antagonize Vit D effect on gut)—> increase in PTH then stimulates osteoclast activity
c. Increase production of RANK-L by OBs and decrease OPG —> Increase OC activation –> increase bone resorption

d. Risk of osteoporosis when GCs used for inflammation
i. Dose and duration dependent
ii. Adequate calcium and Vit D intake essential

e. Plus GCs suppressive effects on osteoblasts

20
Q

Non-Nutritional Factors Associated w/ BMD

A
  1. Initial bone mineral density
    peak bone mass (PBM)
    heredity (~ 70 - 80% variability in PBM)
  2. Hypogonadism (esp. decreased estrogen)
  3. Age – strongest empiric predictor of BMD
  4. Medications (esp corticosteroids)
    a) glucocorticoids, immobility, gastrectomy
    b) Chronic illnesses – associated w/ malabsorption, chronic systemic inflammation;
    c) Magnitude of steroid use = single strongest predictor of osteopenia pts w/ inflammatory bowel disease (both ulcerative colitis & Crohn’s disease); obesity
  5. Behaviors/lifestyle
    i. Tobacco & Alcohol – depress osteoblast activity, impair nutrition

ii. Weight bearing exercise:
- Muscle mass directly related to bone mass
- Mechanosensors on bone regulate (increase) osteocyte and osteoblast activity

21
Q

Adverse Reactions – Warfarin - CVPR

Warfarin is Vitamin K antagonist

A

a. Hemorrhage
b. Necrosis of fatty soft tissue (esp. females in 1st 10 days of therapy, [?] decrease in protein C)
c. GI (nausea, vomiting, diarrhea, cramping); ***osteoporosis
d. Contraindicated in pregnancy (crosses placenta); other contraindications similar to heparin

22
Q

Osteoporosis Prevention and Treatment

A

a. Calcium: 1000-1500 mg/day
i. Dairy Products (CaPO4): ~ 300 mg/serving
ii. Supplements if Dairy Intake Insufficient

b. Vitamin D: 1000 units/day
c. Exercise: Aerobic and Resistance
d. Fall Assessment and Prevention

23
Q

Osteoporosis Treatment

A

a. Anti-Resorptive Agents:
1. Bisphosphonates
2. Denosumab
3. Raloxifene
4. Calcitonin
5. Estrogens

b. Anabolic Agents
1. Teriparatide

24
Q

Prevention & Treatment of Osteoporosis

Bisphosphonates (BPs)

A

Alendronate, Risedronate, Ibandronate, Zoledronate

Mechanism of Action
a. Pyrophosphate analogs with high affinity for bone at Ca-P interface

b. BPs bind to active sites of bone remodeling—> direct inhibitory effects on OC
i. Induce osteoclast apoptosis
ii. Inhibits prenylation of proteins necessary for OC fxn
iii. Buried in bone, recycled when resorptive site undergoes remodeling – may persist 10+ years

25
Q

lendronate, Risedronate, Ibandronate, Zoledronate

A

Bisphosphonates (BPs)

Mechanism of Action
a. Pyrophosphate analogs with high affinity for bone at Ca-P interface

b. BPs bind to active sites of bone remodeling—> direct inhibitory effects on Osteoclasts
i. Induce osteoclast apoptosis
ii. Inhibits prenylation of proteins necessary for OC fxn
iii. Buried in bone, recycled when resorptive site undergoes remodeling – may persist 10+ years

c. Role in Osteoporosis: Currently the most effective drugs for treatment and prevention of osteoporosis

26
Q

Bisphosphonates (BPs) Pharmcokinetics and ADR

lendronate, Risedronate, Ibandronate, Zoledronate

A

a. Pharmacokinetics
* i. 1-10% absorbed orally–> half to bone, half excreted
ii. Q week formulations for alendronate / risedronate
iii. Q month / Q 3 month for ibandronate (IV)
iv. Q year for zoledronate (IV)

b. Adverse Reactions
i. GI irritation, esp. esophagitis-special administration technique
ii. Severe bone, joint, and / or muscle pain has been observed - rarely *osteonecrosis of the jaw

c. Role in Osteoporosis: Currently the most effective drugs for treatment and prevention of osteoporosis

27
Q

lendronate, Risedronate, Ibandronate, Zoledronate

Mechanism and ADR

A

Bisphosphonates (BPs)

a. BPs bind to active sites of bone remodeling—> direct inhibitory effects on Osteoclasts*

b. Adverse Reactions
1. *GI irritation, esp. esophagitis-special administration technique
2. Severe bone, joint, and / or muscle pain has been observed - rarely *osteonecrosis of the jaw

c. Role in Osteoporosis: Currently the most effective drugs for treatment and prevention of osteoporosis –> for how long??

28
Q

Prevention & Treatment of Osteoporosis

SERM - Raloxifene

A

SERM - Raloxifene
SERM (Bazedoxifene) + Estrogen

a. SERMs (selective estrogen receptor agonists) are agonists on bone-liver, inactive-antagonist on uterus, antagonist on breast

b. SERMs reduce risks of osteoporotic fractures, but less efficacy than estrogen (or bisphosphonates)
i. SERM + estrogen combo showed greater increases in BMD than SERM alone

c. Advantages relative to estrogen:
i. Reduced risk of breast cancer and coronary events

d. Disadvantage relative to estrogen:
i. Worsening of menopausal vasomotor symptoms, leg cramps with raloxifene
- NOT with SERM + estrogen (obviously) which also has indication for menopausal symptoms

ii. Risk of breast-endometrial-ovarian cancer about 0%
iii. Risk of VTE disorders (agonist on liver) similar to estrogen – expected to be similar with Duavee
e. Role in Osteoporosis: Choice in patient intolerant of bisphosphonates and at increased invasive breast cancer risk

29
Q

Why use Raloxifene over Estrogen?

A

SERM - Raloxifene

a. SERMs (selective estrogen receptor agonists) are agonists on bone-liver, inactive-antagonist on uterus, antagonist on breast

b. SERMs reduce risks of osteoporotic fractures, but less efficacy than estrogen (or bisphosphonates)
i. SERM + estrogen combo showed greater increases in BMD than SERM alone

c. Advantages relative to estrogen:
i. Reduced risk of breast cancer and coronary events

d. Role in Osteoporosis: Choice in patient intolerant of bisphosphonates and at increased invasive breast cancer risk

30
Q

Advantages and Disadvantages of

SERM - Raloxifene
SERM (Bazedoxifene) + Estrogen

A

SERM - Raloxifene
SERM (Bazedoxifene) + Estrogen

a. Advantages relative to estrogen:
i. Reduced risk of breast cancer and coronary events

b. Disadvantage relative to estrogen:
1. Worsening of menopausal vasomotor symptoms, leg cramps with raloxifene
i. NOT with SERM + estrogen (obviously) which also has indication for menopausal symptoms

  1. Risk of breast-endometrial-ovarian cancer about 0%
  2. Risk of VTE disorders (agonist on liver) similar to estrogen – expected to be similar with Duavee
    c. Role in Osteoporosis: Choice in patient intolerant of bisphosphonates and at increased invasive breast cancer risk
31
Q

Prevention & Treatment of Osteoporosis

Estrogens

A

a. *Reduce bone resorption via inhibitory effects on osteoclasts
i. Most effective given within first 5 years after menopause

b. *Reduced enthusiasm for estrogen use following WHI report
i. Positive benefit: preserving bone and preventing osteoporotic fractures
ii. Outweighed by: Increased risk of heart disease, breast cancer, stroke, VTE

c. Role in osteoporosis: Estrogen (as MHT) for osteoporosis prevention should be limited to women with significant vasomotor symptoms who are not at risk for heart disease

32
Q

Reduced enthusiasm for estrogen use following WHI report

A
  1. Positive benefit: preserving bone and preventing osteoporotic fractures
  2. Outweighed by: Increased risk of heart disease, breast cancer, stroke, VTE

Role in osteoporosis: Estrogen (as MHT) for osteoporosis prevention should be limited to women with significant vasomotor symptoms who are NOT at risk for heart disease

33
Q

Prevention & Treatment of Osteoporosis

Denosumab

A

Denosumab

a. Mechanism of Action
i. Humanized monoclonal antibody against RANKL–> reduces osteoclast activation improving bone mineral density

b. Pharmacokinetics
i. Subcutaneous injection every six months

c. Adverse Reactions
i. Generally well tolerated – hypocalcemia possible

d. Role in osteoporosis: Treatment of patients at high risk for fractures - intolerant or non-responsive to other therapies

34
Q

Denosumab

A

a. Mechanism of Action
i. Humanized monoclonal antibody against RANKL–> reduces osteoclast activation improving bone mineral density

b. Pharmacokinetics
i. Subcutaneous injection every six months

c. Adverse Reactions
i. Generally well tolerated – hypocalcemia possible

d. Role in osteoporosis: Treatment of patients at high risk for fractures - intolerant or non-responsive to other therapies

35
Q

Prevention & Treatment of Osteoporosis

Calcitonin

A

Calcitonin

a. Mechanism of Action
i. *Inhibition of osteoclastic bone resorption
ii. Modest increase in bone mass – less effective than BPs-PTH

b. Pharmacokinetics
i. Given via* nasal spray
ii. or *SC

c. Adverse Reactions
i. Nausea, hand-swelling, urticaria
ii. Concern with increase in cancer rates with long-term use

d. Role in osteoporosis: Approved by FDA for treatment, but not prevention, of osteoporosis – use is declining

36
Q

Calcitonin

A

a. Mechanism of Action
i. *Inhibition of osteoclastic bone resorption
ii. Modest increase in bone mass – less effective than BPs-PTH

b. Pharmacokinetics
i. Given via* nasal spray
ii. or *SC

c. Adverse Reactions
i. Nausea, hand-swelling, urticaria
ii. Concern with increase in cancer rates with long-term use

d. Role in osteoporosis: Approved by FDA for treatment, but not prevention

37
Q

Prevention & Treatment of Osteoporosis

Teriparatide Mechanism

A

Teriparatide
Mechanism of Action

a. *Only agent for treatment of osteoporosis that stimulates bone formation - all other treatments are antiresorptive
* b. Continuous high levels –> bone demineralization and osteopenia
* c. Intermittent administration—> Increased osteoblastic activity and bone formation
* Role in osteoporosis: Treatment of severe osteoporosis in postmenopausal women and men at high risk of fractures

38
Q

Teriparatide

Pharmacokinetics and ADR

A

a. Pharmacokinetics
i. *Daily subcutaneous dose
ii. Peak levels at 30 minutes that the decline to undetectable within 3 hours

b. Adverse Reactions
i. Nausea, headache, dizziness, muscle cramps

c. Role in osteoporosis: Treatment of severe osteoporosis in postmenopausal women and men at high risk of fractures

39
Q

Teriparatide Summary points

A

a. *Only agent for treatment of osteoporosis that stimulates bone formation - all other treatments are antiresorptive
* i. Continuous high levels –> bone demineralization and osteopenia
* ii. Intermittent administration—> Increased osteoblastic activity and bone formation

b. Pharmacokinetics
i. *Daily subcutaneous dose

c. Adverse Reactions
i. Nausea, headache, dizziness, muscle cramps

d. Role in osteoporosis: Treatment of severe osteoporosis in postmenopausal women and men at high risk of fractures

40
Q

Hypercalcemia of Malignancy**Treatment

Other lecture

A

a. Promote Urine Calcium Excretion
i. Saline Infusion

b. Inhibit Bone Resorption
i. IV Bisphosphonates
ii. Denosumab
iii. Calcitonin
iv. Plicamycin

c. Remove Calcium
i. Dialysis

41
Q

Treatment of Hypercalcemia

A

a. Saline diuresis** (± furosemide, a loop diuretic):
i. Early and aggressive fluid resuscitation
ii. Loop diuretics Increase Ca++ excretion + counter volume expansion if renal insufficiency or heart failure

b. Bisphosphonates** (preferred in hypercalcemia of malignancy, response within 2d, lasting weeks):
1) Zoledronate–> given over 5-15 min
2) Pamidronate–> IV over 2-4 hours is choice

  1. Calcitonin** :
    i. Given SC, rapid decrease in Ca++ (within 4-6 hours)
    ii. Efficacy limited to 48 hours (tachyphylaxis)
  2. Plicamycin**
    i. Cytotoxic antibiotic, NOT 1st choice due to toxicity
    ii. Used if other agents fail (acts within 24-48 hrs)
  3. Glucocorticoids (usually high dose prednisone)
    i. Useful in chronic hypercalcemia (granulomatous in origin–> sarcoidosis, lymphoma, or increased Vit D)
    ii. Response to glucocorticoids is slow (1-2 weeks)
  4. Phosphates
    i. Via oral route for short-term control (pre-surgery for HPT)
    ii. IV route is fastest, surest reduction, BUT too risky unless patient is also hypophosphatemic
42
Q

Hypocalcemia Major Causes

A

a. Major causes: hypoparathyroidism, Vitamin D deficiency, renal failure (via decreased synthesis of calcitriol), malabsorption, hypomagnesemia

b. Primary symptoms are neuromuscular
i. Tetany, paresthesias, muscle cramps, convulsions may be present if hypocalcemia develops acutely

c. Treatment varies depending on severity and underlying cause
i. Absolute level of calcium as well as rate of decrease determine severity of symptoms

43
Q

Treatment of Acute Hypocalcemia

A

Severe hypocalcemic tetany

    1. Calcium gluconate: treatment of choice, IV over 4-6 hours
      1. Calcium chloride: less desirable, vein irritation, peripheral vasodilation
      2. Calcium gluceptate: can be given intramuscularly.
    1. Oral calcium salts are sufficient (with vitamin D) for milder symptoms or in asymptomatic patient

NOTE: Serum Mg++ levels should be normalized if low (necessary for PTH actions)

44
Q

Supplements of Calcium

A
  1. Calcium carbonate (e.g. TUMS)
    i. Maximum elemental Ca/tablet (40%);
    ii. 1250 mg = 500 mg Ca
    iii. Best absorbed w/ meals (30%)
    iv. Least lead
  2. Calcium citrate malate
    i. 21% elemental Ca
    ii. Best absorbed between meals (36%)

*43% of Americans (70% of older women) consume Ca supplements