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Pharmacology > Bone Homeostasis > Flashcards

Bone Homeostasis Flashcards

0
Q

PTH on bone

A

⬆️activity and number of osteoclasts ➡️release of calcium and phosphate

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1
Q

what stimulates PTH secretion

A

fall in plasma ionized calcium level

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2
Q

PTH on kidney

A

⬆️tubular resorption of calcium and magnesium
⬇️absorption of phosphate, amino acid, bicarbonate, sodium chloride and sulfate
stimulation of 1,25 DH vit D

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3
Q

metabolic active form of vit D

A

1,25 OH2D

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4
Q

enzyme that catalyzes formation of 1,25 OH2D from 25 OHD

A

1 hydroxylase

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5
Q

PT gland contains

A

ca sensitive protease
ca sensing receptor
vit D receptor and CYP27B1

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6
Q

ca sensitive protease

A

cleaves PTH

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7
Q

ca sensing receptor

A

reduces PTH production when stimulated by Ca

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8
Q

vit D receptor and CYP27B1

A

produces active metabolite of vit D, ⬇️PTH

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9
Q

1,25 DH vit D on bone

A

release of calcium and phosphate

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10
Q

1,25 DH vit D on intestine

A

⬆️Ca absorption

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11
Q

1,25 DH vit D on kidneys

A

reabsorption of calcium and phosphate

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12
Q

phosphaturic hormone

A

FGF 23

fibroblast growth factor 23

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13
Q

FGF 23 on kidney

A

inhibits phosphate reabsorption

inhibits 1,25 DH vit D production

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14
Q

FGF 23 on phosphate level

A

hypophosphatemia

➡️inhibition or defective mineralization of bone

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15
Q

primary site of production of FGF 23

A

osteoblasts

osteoclasts

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16
Q

low 1,25 DH vit D level impact by FGF 23

A

absorption of calcium thus there will be lower levels of calcium

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17
Q

phospate on PTH

A

regulates PTH secretion : form complexes with ca➡️ ⬇️Ca stimulates PTH secretion

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18
Q

high phosphate levels stimulate

A

FGF 23 production➡️

phosphate excretion

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19
Q

recombinant human PTH

only FDA approved bone forming drug

A

TERIPARATIDE

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20
Q

TERIPARATIDE on bone

A

stimulates the osteoblasts to induce RANK ligand that acts on osteoclasts and precursors to increase their number and activity

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21
Q

TERIPARATIDE on kidneys

A

increases reabsorption of calcium and magnesium

decreasing the reabsorption of phosphate, aa, HCO3,
➡️stimulates 1,25 DH vit D formation

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22
Q

effects of PTH- TERIPARATIDE

A

elevates serum calcium level

lowers serum phosphate level

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23
Q

TERIPARATIDE form of admin

A

multiple doses of pre filled pen

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24
Q

moa of TERIPARATIDE

A

receptor binding increases cAMP

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25
Q

physiologic effect of PTH

A

bone resorption

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26
Q

pharmacologic effect of PTH: low intermittent dose

A

bone formation by stimulation of osteoblasts and inc collagen synthesis

inc skeletal mass and bone strength

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27
Q

uses of TERIPARATIDE

A

postmenopausal osteoporosis
glucocorticoid induced osteoporosis
primary hypogonadism in men

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28
Q

TERIPARATIDE duration of use

A

2 years only

to prevent risk of osteosarcoma

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29
Q

AE of TERIPARATIDE

A 
nausea
vomiting
constipation
lethargy
muscle weakness
hypercalcemia
hypercalciuria
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30
Q

TERIPARATIDE CI

A

Paget’s dse of bone
cancer metastasis to bone
open epiphysis- children, young adults

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31
Q

absorption of vit d

A

intestines

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32
Q

first conversion of vit D by

A

25 hydroxylase

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33
Q

conversion by 1 hydroxylation

A

1,25 DH Vit D

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34
Q

conversion by 24 hydroxylation

A

24,25 DH vit d

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35
Q

storage of vit D

A

adipose tissue

liver

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36
Q

vit D clearance

A

liver

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37
Q

moa of vit d

A

receptor binding @➡️ gene transcription or repression

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38
Q

increase transcription by vit d

A

vit d receptor gene
calbindin gene
24 hydroxylase enzyme

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39
Q

vit D on the intestine

A

induction of new protein synthesis

  • calcium binding CHON
  • intestinal calcium channel

result: enhanced calcium absorption

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40
Q

vit D on bone

A

stimulates bone resorption - needs PTH

mineralization of newly formed osteoid

induces osteocalcin synth in osteoblasts

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41
Q

marker for osteoblastic bone formation

A

osteocalcin

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42
Q

vit D on kidney

A

increase calcium pumps ➡️ decrease calcium excretion

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43
Q

vit D on keratinocytes

A

calcitriol stimulates differentiation

inhibits proliferation

formation of cornified layer of epidermis ➡️psoriasis

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44
Q

vit D on PTH

A

decrease levels

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45
Q

vit D on immunity

A

promote innate immunity

inhibit adaptive immunity

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46
Q

vit D prohormones

A

cholecalciferol - vit D3

ergocalciferol - vit D2

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47
Q

vit d metabolite

A

calcitriol- 1,25 DH vit D

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48
Q

vit D analogs

A

paricalcitol

doxecalciferol

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49
Q

dihyrdrocalciferol

A

can increase calcium in 24-48 hours

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50
Q

vit d nutritional deficiency

A

rickets

osteomalacia

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51
Q

defective mineralization in growing bone

A

rickets

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52
Q

softening and weakening of bone

A

osteomalacia

53
Q

hypocalcemia tx

A

vit D or calcitriol with calcium

54
Q

hypoparathyroidism cause

A

idiopathic or surgical

leads to 1,25 DH vit D decrease

55
Q

secondary hypoparathyroidism of chronic renal disease tx

A

calcitriol
doxecalciferol
paricalcitol

56
Q

malabsorption of vit d and calcium

A

intestinal osteodystrophy

57
Q

nephrotic syndrome causes

A

loss of vitamin D binding protein

58
Q

vit D AE

A

hypercalcemia
hypercalciuria
renal calculi- calcium phosphate deposits
hyperphosphatemia

59
Q

calcitonin source

A

parafollicular cells of the thyroid gland

60
Q

moa of calcitonin

A

receptor binding➡️ increase cAMP

61
Q

calcitonin on bone

A

inhibits osteoclastic bone resorption

62
Q

calcitonin on kidney

A

decrease calcium and phosphate reabsorption

63
Q

calcitonin on GI

A

⬇️gastrin secretion and gastric acid output

⬆️secretion of Na, K, Cl and water in gutw

64
Q

overall effect of calcitonin

A

decrease serum calcium and serum phosphate

65
Q

calcitonin prep

A

salmon calcitonin

66
Q

Properties of salmon calcitonin

A

greater potency per miligram

longer duration of action

67
Q

salmon calcitonin routes of admin

A

nasal spray

injection

68
Q

tachyphylaxis by calcitonin in 48-72 hours is due to

A

receptor downregulation

69
Q

uses of Calcitonin

A

Paget’s dse of bone (osteitis deformans)
osteoporosis
hypercalcemic emergency due to CA, multiple myeloma, primary hyperparathyroidism

70
Q

AE of calcitonin

A 
hypersensitivity
athralgia
rhinitis, epistaxis, sinusitis
rash and facial flushing
malaise
transient marked increase in sodium and water excretion
71
Q

glucocorticoids on GI

A

inhibit intestinal absorption of calcium

72
Q

GC on kidney

A

promote renal excretion of calcium

73
Q

GC on bone

A

loss of calcium

74
Q

GC indications

A

hypercalcemia of malignancy, sarcoidosis, hypervitaminosis

75
Q

GC on malignancy

A

decrease tumor mass and activity- lymphoma, mM

inhibit cytokines that stimulate osteoclasts

76
Q

GC on sarcoidosis

A

decrease sarcoid tissue mass that produces high levels of 1,25 DHD

77
Q

GC on hypervitaminosis

A

decrease intestinal calcium absorption mediated by vit D

78
Q

AE of gc

A

stunted growth

osteoporosis

79
Q

effect of estrogen on bone

A

inhibits bone resorption of PTH

preserve bone after menopause

80
Q

estrogen on breast and endometrium

A

stimulation

81
Q

estrogen use

A

not first line drug

prevent or treat postmenopausal osteoporosis

82
Q

estrogen concerns

A

carcinoma

thromboembolism

83
Q

estrogen on serum calcium and phosphate levels

84
Q

estrogen on calcitriol

85
Q

synthetic steroid derived from 19 nortestosterone

86
Q

estrogen effects of TIBOLONE

A

relieves urogenital and vasomotor symptoms

prevents bone loss

87
Q

anti estrogen effect of TIBOLONE

A

prevents uterine and breast stimulation

88
Q

advantage of TIBOLONE

A

no need to add progestin

89
Q

TIBOLONE indications

A

relieve menopausal symptoms

prevent postmenopausal osteoporosis

90
Q

AE of TIBOLONE

A 
vaginal bleeding, spotting, discharge
breast pain
nausea, vomiting
headache
weight gain
91
Q

RALOXIFENE Action on bone

A

preVents bone resorption

92
Q

RALOXIFENE on breast and endometrium

A

prevents stimulation

93
Q

raloxifene effects

A

increases bone density

94
Q

RALOXIFENE classification

A

selective estrogen receptor modulator

95
Q

RALOXIFENE on lipid

A

decrease LDL c and total cholesterol

96
Q

RALOXIFENE indications

A

prevent or treat postmenopausal osteoporosis

decrease risk of invasive breast ca in postmenopausal osteoporotic women

97
Q

RALOXIFENE AE

A

hot flushes
leg cramps
peripheral edema
deep vein thrombosis

98
Q

moa of bisphosphonates

A

bind to hydroxyapatite in bone, preferential localization to bone resorption sites

99
Q

BISPHOSPHONATES on bone

A

suppress osteoclast activity, inhibiting bone formation

retard formation and dissolution of hydroxyapatite, gradually released from bone

100
Q

RALOXIFENE indications

A

Paget’s dse of bone
hypercalcemia of malignancy
osteoporosis

101
Q

bisphosphonates for hypercalcemia of malignancy

A

PAMIDRONATE

ZOLEDRONIC ACID

102
Q

less potent first gen bisphosphonate

A

ETIDRONATE

103
Q

2nd gen bisphosphonate

A

ALENDRONATE

104
Q

3rd gen bisphosPhonate

A

ZOLEDRONATE

105
Q

AE of bisphosphonates

A 
adynamic bone
osteonecrosis of jaw 
possible renal failure
metallic taste
hyperphosphatemia
inhibition of bone mineralization
106
Q

CI bisphosphonates

A

esophageal motility disorders
PUD
decrease renal fxn

107
Q

IV prep

A

IBANDRONATE- bolus, q3 months

ZOLEDRONIC ACID- reclast 5 mg, yearly infusion

108
Q

oral bisphosphonates should be taken

A

on an empty stomach
with 6-8 oz of water
no food or drink for 30-60 minutes
upright position

109
Q

levels checked before IV dose of bisphosphonates

A

creatine

calcium

110
Q

calcimimetic

A

CINACALCET

111
Q

action of CINACALCET

A

activate calcium sensing receptors to block the release of PTH

112
Q

uses of CINACALCET

A

secondary hyperparathyroidism in chronic renal dse
parathyroid ca
primary hyperparathyroidism who are unable to undergo parathyroidectomy

113
Q

naturally occuring mineral deposited in bone

A

STRONTIUM RANELATE

114
Q

STRONTIUM RANELATE actions

A

suppresses bone resorption by inhibiting osteoclast differentiation

115
Q

PHOSPHATE AE

A

GI

hypocalcemia, hypotension, shock, acute MI, tetany, ectopic calcification

116
Q

PHOSPHATE actions

A

promote calcium deposition in the bone and soft tissue

reduce calcium absorption

117
Q

PHOSPHATE CI

A

impaired renal flow
hyperphosphatemia
alkaline urine secondary to UTI

118
Q

PHOSPHATE drug interactions

119
Q

phosphate prep

A

Potassium phosphate injection
sodium phosphate injection
sodium phosphate tablet or oral solution

120
Q

PHOSPHATE indications

A

hypercalcemic crisis- slowly
phosphate deficiency
- x linked hypophosphatemia
- autosommal dominant hypophosphatemia

121
Q

indication for IV calcium

A

severe hypocalcemia

-tetany, laryngospasm

122
Q

IV calcium prep

A

calcium cl 27%
calcium gluceptate 8%
calcium gluconate 9%

123
Q

preferred IV because less irritating to veins

A

calcium gluconate

124
Q

risks of iv calcium

A

arrhythmias
local vein irritation, abscess formation
precipitation, calcification
ectopic calcification

125
Q

oral calcium indications

A

mild hypocalcemia

osteroporosis

126
Q

oral calcium prep

A

ca carbonate 40%
ca citrate 21%
ca lactate 13%
ca gluconate 9%

127
Q

more readily available oral calcium with high content

requires food

A

calcium carbonate 40%

128
Q

better absorbed oral calcium

A

calcium citrate

129
Q

ADR of calcium

Pharmacology (8 decks)

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