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Pharmacology Test #5 > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

Calcium in the bone is

A

hydroxyapatite [Ca10(PO4)6(OH)2]

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2
Q

Osteoblasts

A

bone forming cells

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3
Q

Osteoclasts

A

bone resorption cells

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4
Q

Factors released by osteocytes that stimulates osteoblasts

A

prostaglandins, NO, dentin matrix protein-1

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5
Q

Factors released by osteocytes that stimulates osteoclasts

A

sclerostin; osteocalcin; MEPE (matrix extracellular phosphoglycoprotein)

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6
Q

What does parathyroid hormone (PTH) do?

A
  1. increased calcium reabsorption from CT
  2. increased calcium resorption from bone
  3. increased PO4 loss in urine
  4. increased 1,25(OH)2D3 production by kidney
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7
Q

PTH secretion is triggered by

A

low serum Ca2+ levels

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8
Q

First step of vitamin D synthesis

A

7-dehydrocholesterol -> (UV) -> cholecalciferol (D3)

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9
Q

Cholecalciferol can be obtained

A

in the diet or via exposure to sun light

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10
Q

Under which conditions is 25-hydyoxyvitamin D3 converted into 1,25 Dihydroxy vit D3 (calcitriol)?

A

low phosphorus and Ca2+

PTH

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11
Q

Under which conditions is 25-hydyoxyvitamin D3 converted into 24,25 Dihydroxy Vit D3 (secalciferol)?

A

normal phosphorus and calcium

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12
Q

What reaction does 1-alpha-hydroxylase catalyze?

A

25-hydyoxyvitamin D3 -> 1,25 Dihydroxy vit D3 (calcitriol)

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13
Q

What reaction does 24-hydroxylase catalyze?

A

25-hydyoxyvitamin D3 -> 24,25 Dihydroxy Vit D3 (secalciferol)

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14
Q

Actions of vitamin D

A
  1. increased calcium and PO4 absorption from small intestine
  2. increased calcium and PO4 reabsorption
  3. indirect (slow) effects on cells
  4. feedback inhibition of PTH (1,25(OH)2D
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15
Q

What is upregulated by Vitamin D3?

A
  1. TrpV6
  2. Calbindin-D9k
  3. Ca2+-ATPase
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16
Q

Which cells secrete calcitonin?

A

cells in the thyroid gland

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17
Q

What does calcitonin do?

A

negative regulator of serum calcium;

  1. inhibits osteoclastic bone resorption
  2. increases calcium and PO4 loss in the urine
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18
Q

What is calcitonin stimulated by?

A

high serum calcium levels

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19
Q

Describe postmenopausal osteoporosis.

A

decrease in estrogen levels causes a decrease in bone mass; shift in bone remodeling balance toward resorption; spontaneous or minimal trauma fractures

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20
Q

Describe osteoporosis related to aging.

A

caused by age-related decrease in osteoblast activity in both men and women

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21
Q

Vertebral complications of osteoporosis

A

fragility fractures; pain; height loss; kyphosis; activity limitations; restrictive lung disease; psychological symptoms

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22
Q

Risk factors for osteoporosis

A

Physical inactivity; age; low calcium intake in early years; long-term glucocorticoid therapy

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23
Q

Hyperparathyroidism

A

increased bone resorption and decreased calcium excretion

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24
Q

Hypercalcemia caused by malignant tumors

A

some tumors produce a peptide with PTH activity

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25
Q

CNS complications from hypercalcemia

A

depression and coma

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26
Q

Hypocalcemia can be caused by

A

hypoparathyroidism or vit. D deficiencies

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27
Q

Symptoms of hypocalcemia

A

causes neuromuscular disturbances, parasthesias, tetany, and muscle cramps

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28
Q

Rickets

A

Vitamin D deficieny; weight bearing bone deformities in children

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29
Q

Vitamin D preparations

A

Cholecalciferol Vit D3 (OTC)
Calcifediol 25(OH)Vit D3 (Calderol)
Calcitriol 1,25(OH)2VitD3 (Rocaltrol)

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30
Q

MOA of Vitamin D supplements

A

increased calcium and PO4 absorption from gut

increased calcium and PO4 reabsorption in renal tubules

31
Q

Pagets disease

A

uncontrolled osteoclastic bone resorption and secondary bone formation

32
Q

Symptoms of Pagets disease

A
  1. bone pain
  2. bone deformities
  3. loss of hearing, hypercalcemia
  4. may be caused by a slowly acting virus
33
Q

How do loop diuretics affect serum Ca2+ levels?

A

increased calcium excretion

decreased driving force for uptake with inhibition of Na+/K+/2Cl- co-transporter

34
Q

How do thiazides affect serum Ca2+ levels?

A

decreased calcium excretion

increased driving force for uptake with inhibition of Na/Cl transporter in the distal tubule

35
Q

How do PPIs and H2 antagonists affect serum Ca2+ levels?

A

decreased acidity of stomach decreases calcium absorption (Omeprazole may inhibit bone resorption)

36
Q

How do carbemazepine, isoniazid, theophylline and rifampin affect Ca2+ levels?

A

induction of Vit. D catabolic P450s

37
Q

First line therapy for osteoporosis

A

Bisphosphonates

38
Q

Bisphosphonates are analogs of what?

A

analogs of inorganic pyrophosphate

39
Q

MOA of bisphosphonates

A

reduce formation and dissolution of hydroxyapatite crystals by accumulating in bone as part of the matrix; disrupt cytoskeleton, induce apoptosis, inhibit farnesyl-PP synthesis of osteoclasts

40
Q

Adverse effects of bisphosphonates

A

NVD, musculoskeletal pain, osteonecrosis of the jaw, atypical femur fractures

41
Q

What do bisphosphates do?

A

reduce formation and dissolution of hydroxyapatite crystals by accumulating in bone as part of the matrix; disrupt cytoskeleton, induce apoptosis, inhibit farnesyl-PP synthesis of osteoclasts

42
Q

Bisphosphonates approved for osteoporosis (builds bone mass)

A

Zoledronate (Reclast)
Alendronate (Fosamax)
Risedronate (Actonel)
Ibandronate (Boniva)

43
Q

MOA of bisphosphates

A

inhibition of farnesyl pyrophosphate synthase; disrupts prenylation of proteins in osteoclasts

44
Q

Second line treatment for osteoporosis

A

Estrogens and SERMs
Calcitonin
Teriparatide (Forteo)

45
Q

What do Estrogens and SERMs do?

A
  1. prevention and control of postmenopausal bone resorption

2. increases activity of osteoblasts, decreases activity of osteoclasts

46
Q

Risks with Raloxifene

A

less cancer risk than estrogen, but risk for VTE and death from stroke

47
Q

Estrogens and SERMs used 2nd line for osteoporosis

A

Estradiol and Raloxifene

48
Q

Calcitonin formulations

A

Calcimar and Miacalcin (salmon)

Cibacalcin (human)

49
Q

What does calcitonin treatment do?

A

decreased osteoclast activity, blocks renal reabsorption of PO4 and calcium

50
Q

Clinical uses of calcitonin

A

Paget’s disease;
hypercalcemia secondary to malignancy;
Osteoporosis

51
Q

Side effects of calcitonin

A

urticaria, hand swelling, nausea

52
Q

What is Teriparatide (Forteo)?

A

amino acids 1-34 of parathyroid hormone produced in E. coli

53
Q

What does Teriparatide do?

A

preferentially stimulates osteoblast activity

54
Q

Clinical uses of Teriparatide

A

for treatment of osteoporosis in patients with a high risk of fracture

55
Q

AEs of Teriparatide

A

orthostatic hypotension, hypercalcemia, arthralgias, allergic reactions

56
Q

What does intermittent dosing of Teriparatide result in?

A

increased osteoblast number/function -> increased bone formation -> increased bone mass/strength

57
Q

What does continuous dosing of Teriparatide result in?

A

increased osteoclast activity; increased bone resorption; increased serum calcium

58
Q

Pros of Teriparatide compared to bisphosphonates

A

may be more effective in preventing fractures than bisphosphates; builds bone mass at a higher rate than bisphosphates; may allow better bone healing after fracture than bisphosphonates

59
Q

Cons of Teriparatide compated to bisphosphonates

A

must be injected daily; not recommended beyond 2 years; black box warning required by FDA for risk of bone cancer

60
Q

Denosumab (Prolia, Xgeva)

A

humanized monoclonal Ab against RANKL

61
Q

MOA of Denosumab

A

binds to RANKL and prevents activation of RANK on osteoclast precursors, preventing differentiation of osteoclasts

62
Q

Clinical use of Denosumab

A

for treatment of osteoporosis in postmenopausal women with a history of fractures, high risk of fractures or intolerance to bisphosphonates

63
Q

What must Denosumab be taken with?

A

patients must take 1000 mg calcium and 400 IU Vit D daily

64
Q

AEs of Denosumab

A

hypocalcemia, osteonecrosis of the jaw, atypical femur fractures, musculoskeletal pain, severe infections, skin reactions

65
Q

Clinical use of Cinacalcet (Sensipar)

A

Primary hyperparthyroidism;
Parathyroid carcinoma;
Secondary HPT in CKD with dialysis

66
Q

MOA of Cinacalcet (Sensipar)

A

binds to calcium-sensing receptor (a GPCR on PTH gland to inhibit release of PTH); allosteric regulator - causes receptor to be more sensitive to calcium

67
Q

Cinacalcet (Sensipar) decreases

A

both serum PTH levels and serum calcium levels

68
Q

Risks with Cinacalcet (Sensipar)

A

risk of hypocalcemia, seizures, adynamic bone disease

69
Q

Analogs of Vitamin D

A

Zemplar and Hectorol

70
Q

Calcific uremic arteriolopathy

A

Calcium can combine with (PO4)3- and precipitate in tissues - calcification

71
Q

Phosphate binders

A

complex with dietary phosphate and prevent absorption from GI

72
Q

Lanthanum Carbonate (Fosrenol)

A

forms insoluble LaPO4 salts in the GI tract; decreases serum (PO4)3- and calcium levels

73
Q

Sevelamer (Renagel, Renvela)

A

Amine-containing polymer that binds (PO4)3- in the GI tract; decreases serum (PO4)3- levels selectively

Pharmacology Test #5 (11 decks)

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