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Respiratory/Musculoskeletal > Ph- Drugs for Disorders of Ca Homeostasis and Bone > Flashcards

Ph- Drugs for Disorders of Ca Homeostasis and Bone Flashcards

1
Q

What are the 3 oral bisphosphonate drugs?

What are the 3 parenteral bisphosphonate drugs?

A

Oral:
Alendronate
Ibandronate
Risedronate

Parenteral:
Zoledronate
Ibandronate
Pamidronate

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2
Q

What is raloxifene?

A

SERM- selective estrogen receptor modulator

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3
Q

What are the 2 ways calcitonin can be delivered?

A

Intranasally and subcutaneously

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4
Q

What is denosumab?

A

A monoclonal antibody to receptor activator of NFkB Lingand (RANKL)

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5
Q

What is teriparatide?

A

a recombinant parathyroid hormone (1-34)

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6
Q

What kind of drugs are calcitriol, paricalcitol, doxercalciferol?

A

Vitamin D analongs

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7
Q

What kind of drugs are sevelamer hydrochloride, sevelamer carbonate and lanthanum carbonate?

A

Phosphorus binders

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8
Q

What kind of drug is cinacalcet?

A

A CaSR agonist that increases sensitivity of the parathyroid to calcium levels.

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9
Q

What drugs are used to treat primary hyperparathyroidism?

1 major, 3 rare

A
  1. CaSR agonist (cinacalcet)

Rarely:

  1. bisphosphonates (oral)
  2. estrogen
  3. SERM
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10
Q

What drugs are used to treat hypercalcemia of malignancy?

4

A
  1. volume repletion
  2. loop diuretics (furosemide)
  3. bisphosphonates (parenteral)
  4. calcitonin
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11
Q

How do you treat hypercalcemia caused by elevated 1,25 (OH)2-D?

(1)

A

glucocorticoids (because you will absorb less Ca from the gut)

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12
Q

How do you treat hypocalcemia caused by hypoparathyroidism OR vitamin D deficiency?

(2)

A
  1. Ca supplements

2. vitamin D analogs (calcitriol, paricalitol, doxercalciferol)

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13
Q

What drugs can be used to treat osteoporosis?

A
  1. Ca supplements
  2. vitamin D analogs
  3. bisphosphonate
  4. SERM
  5. monoclonal AB to RANKL
  6. recombinant PTH (1,34)
  7. calcitonin - third line
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14
Q

What drugs are used to treat secondary hyperparathyroidism caused by CKD?

A
  1. Vitamin D analogs
  2. phosphorus binders
  3. CaSR
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15
Q

What are the 2 major complications associated with primary hyperparathyroidism?

A
  1. kidney stones

2. decreased BMD

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16
Q

What should treatment be if Ca levels are :

  1. below 12
  2. 12-14
  3. > 14
A
  1. hydration
  2. hydration or urgent care depending on symptoms
  3. urgent therapy
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17
Q

How does calcitonin lower Ca?

What drug is it used as an adjunct to?

A

It inhibits bone resorption and thus acutely lowers serum Ca concentration.

It is used with bisphosphonates with severe hypercalcemia

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18
Q

How does cinacalcet lower serum Ca?

A

It is an allosteric modulator of the CaSR at the level of parathyroid cells.
It will inhibit PTH secretion.

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19
Q

How do glucocorticoids lower Ca?

When are they used?

A

They are used with mult. myeloma, sarcoidosis, and lymphomas that have extrarenal secretion of 1a-hydroxylase (excess 1,25 (OH)2-D)

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20
Q

What is the major cause of hospital hypocalcemia?

A

surgical hypoparathyroidism (after surgical removal)

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21
Q

For severe hypocalcemia, (tetany or seizures) what is the first line of treatment?

What is the preferred treatment for chronic hypocalcemia?

A

IV Ca supplementation
Ca gluconate&raquo_space; Ca chloride because calcium chloride can cause severe necrosis and sloughing of perivascular tissue

Chronic is treated with oral Ca

22
Q

What is the difference between Ca carbonate and Ca citrate?

A

Carbonate requires sufficient gastric acid to allow it to dissolve prior to absorption.This means it must be taken at meals.

Cirtrate has better bioavailability and is not influenced by stomach acid secretion

23
Q

A patient comes in and with chronic hypocalcemia. He is on a PPI for peptic ulcers. What form of oral calcium should he take?

A

Calcium citrate because it can be independent of food and gastric acid

24
Q

What diuretic is sometimes used in conjunction with Ca and vitamin D supplements to spare Ca?

25
Q

What is conservative treatment of osteoporosis?

A

Calcium supplements and vitamin D replacement

26
Q

When are other pharmacological therapies besides vit D analogs and calcium supplements used for osteoporosis?

A
  1. patients >50
  2. prior hip or spine fracture
  3. osteoporosis according two T score
  4. osteopenia according to T score
27
Q

What is the mechanism by which bisphosphonates work?

How do first, second and third generation drugs differ?

A

They are pyrophosphate analogs with PCP backbone.

First generation drugs:
They bind hydroxyapatite (the main constituent of bone) and deposit.
Osteoclasts digest them as if they are digesting bone, and apoptosis is triggered.

Second generation have nitrogen side groups (alendronate, pamidronate)
Third generation (risedronate, ibandronate, zolendronate)
Modulate osteoclast activity by binding and blocking farnesyl diphosphate synthase (FPPS)

28
Q

What are the 5 situations where you would use bisphosphonates?

A
  1. hypercalcemia of malignancy- PZ
  2. osteoporosis- AIRZ
  3. Primary hyperthyroidism - AIR
  4. Cancer- PZ
  5. Paget’s disease- ZAR
29
Q

What are the major adverse effects of bisphosphonates?

A
  1. Esophageal irritation- take on empty stomach with water, sit upright for 30 minutes
  2. hypocalcemia in patients with low vit D
  3. osteonecrosis of jaw in patients with metastatic bone disease
  4. atypical femoral fractures
  5. impaired renal function
30
Q

What is the mechanism of action of SERMS?

A

Raloxifene interacts with estrogen receptors A and B.

In bone it is an agonist, and in breast it is an antagonist

31
Q

What are the indications of using a SERM?

A

Raloxifene is used to treat:

  1. osteoporosis
  2. decrease vertebral fractures
  3. prevent breast cancer (not treat current breast cancer)
32
Q

What are the 3 major adverse effects of raloxifene?

A
  1. hot flashes
  2. DVT
  3. leg cramps
33
Q

What is the mechanism of action of calcitonin?

A

It interacts with its own receptor on osteoclasts to inhibit bone resorption.

34
Q

What are the indications for using calcitonin?

A
  1. postmenopausal osteoporosis
  2. hypercalcemia
  3. Paget’s
35
Q

What are adverse effects of intranasal calcitonin?

Subcutaneous?

A

Intranasal- congestion and irritation

SubQ- GI complications

36
Q

What is the mechanism of action of denosumab?

A

IT is a monoclonal antibody to RANKL that inhibits it from activating RANK on the osteoclast to push it to differentiation.

37
Q

What are the indications of using denosumab?

A
  1. men and postmenopausal women osteoporosis at high risk for fracture
  2. patients who have failed other clast inhibiting drugs
38
Q

What are the adverse effects of denosumab?

A
  1. hypocalcemia
  2. infection (at skin site of injection)
  3. osteonecrosis of the jaw
39
Q

What 2 drugs can cause osteonecrosis of the jaw?

A
  1. bisphosphonates

2. denosumab

40
Q

What is the mechanism of action of teriparatide?

A

Anabolic actions with a direct effect of PTH on osteoblast lineage cells mediated by growth factors and ILGF-1

41
Q

What are the adverse effects of teriparatide?

A
  1. increased risk for osteosarcoma in patients with: Pagets
    elevated alk phos
    open epiphyses
    prior skeletal radiation
  2. increased risk of nephrlithiasis
42
Q

What are the 2 associated skeletal abnormalities found with CKD?

A
  1. high bone turnover with excessive resorption and unmatched bone formation due to secondary hyperparathyroidism
  2. low bone turnover with defective bone formation related to osteomalacia or adynamic bone diseases
43
Q

What is the first generation vitamin D analog? What is its structure?
What are the side effects?

A

Calcitriol is a 1,25 (OH)2-D analog that binds VDR with an affinity MUCH higher than the newer generation drugs.

because it binds with such high affinity, the side effects are:

  1. hypercalcemia
  2. hyperphosphatemia
44
Q

What are the second and third generation vitamin D analogs?

A

Second- doxercaciferol

Third- paricalcitol that reduces PTH with a less frequent rise in Ca and P

45
Q

What are the indications for vitamin D analogs?

A
  1. vitamin D deficiency
  2. hypocalcemia due to hypoparathyroidism
  3. prevent/treat Rickets/osteomalacia
  4. secondary hyperparathyroidism with CKD
46
Q

What are the adverse effects of vit. D analogs?

A

increased serum Ca and P that can lead to extraskeletal calcification

47
Q

What is the goal and mechanism of action of phosphate binders?

A

Phosphate binders attempt to limit the intestinal absorption of phosphorus and increase fecal phosphorus excretion to lower serum phosphorus concentration.
Sevelamer hydrochloride and carbonate and lanthanum carbonate bind phosphorus in the intestinal lumen

48
Q

What are the adverse effects of phosphorus binders?

A
  1. increase the risk for hypercalcemia and extraskeletal calcification
  2. diarrhea
  3. metabolic acidosis
49
Q

What is the mechanism of action of cincalcet?

A

It is a CaSR agonist that changes changes in the configuration to increase sensitivity to Ca.
This inhibits PTH secretion acutely (within hours instead of several days like vit D agonists)

50
Q

What are the major indications for cincalcet?

A
  1. reduce PTH in patients with CKD without a rise in Ca or P (like you would get with vit D analogs)
  2. parathyroid carcinoma with SEVERE PTH elevation
  3. parathyroid adenoma primary hyperparathyroidism
51
Q

What are the adverse effects of cincalcet?

A 
hypocalcemia
GI complications (nausea, vomiting)

Respiratory/Musculoskeletal (36 decks)

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