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Endrocrine Exam 2 > Pharmacology: PTH and Osteoporosis > Flashcards

Pharmacology: PTH and Osteoporosis Flashcards

1
Q

What kind of effect does PTH have?

A

Paradoxical

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2
Q

In response to lowered plasma calcium,what is stimulated?

A

Bone resportion
Calcium reabsorption by kidney
Calcitriol in kidney to increase calcium absorption from intestines

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3
Q

What is the paradoxical effect of PTH (opposite increasing calcium)?

A

Stimulates mature osteoblasts via cAMP to have an anti-apoptotic effect and induces mature osteoblast formation

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4
Q

How does PTH induce mature osteoblast formation?

A

Stimulated release of IGF-1

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5
Q

PTH can be what 2 things in bone?

A

Catabolic or anabolic

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6
Q

What determines if PTH is catabolic or anabolic in bone?

A

How long exogenous PTH contacts PTH receptors

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7
Q

What yields more bone formation that resportion with PTH?

A

Brief, intermitten doses (1-3 hours)

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8
Q

So what will once daily PTH dosing do?

A

Increase bone mass

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9
Q

What does continuous elevation of PTH result in?

A

Net bone loss for hyperparathyroidism

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10
Q

What is biologically active human PTH?

A

Teriparatide

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11
Q

What are the 2 uses for teriparatide?

A
  1. Postmenopausal osteoporosis

2. Increase bone mass in men with primary or hypogonadal osteoporosis

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12
Q

What happens in chronic kidney disease or chronic hyperphosphatemia?

A

Excess plasma phosphate complexes with calcium to deplete calcium and lead to hyperparathyroidism

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13
Q

What are the 2 pathways of chronic kidney disease to hyperparathyroidism?

A
  1. Chronic kidney disease –> Decreased Ca receptors on PTH cells and increased set point for Ca regulation –> Hyperparathyroidism
  2. Chronic kidney disease –> Decreased Vit. D –> Decreased GI absorption of calcium –> Decreased plasma Ca –> Increased PTH –> Hyperparathyroidism
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14
Q

What is common in secondary hyperparathyroidism and can be a good drug target?

A

Low vitamin D

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15
Q

What are 2 vitamin D analogues that can be used for secondary hyperparathyroidism?

A
  1. Calcitriol- D3

2. Paricalcitol- D2

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16
Q

When can you use calcitriol?

A

When hyperphosphatemia is controlled, so it doesn’t cause increased calcium and phosphates

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17
Q

What is cinacalcet?

A

Calcimimetic

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18
Q

How does cinacalcet work?

A

Binds to the transmembrane region of the calcium-sensing receptor in the PTH and increases sensitivity of it to calcium

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19
Q

What are the 2 approved uses for cinacalcet?

A
  1. Secondary hyperparathyroidism

2. Hypercalcemia associated with parathyroid carcinoma

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20
Q

Where do vitamin D analoges and cinacalcet work?

A

LOOK AT PICTURE

-Increase Vit D levels/increase sensitivity to Ca

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21
Q

What are 2 oral phosphate binders?

A

Calcium carbonate and calcium acetate

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22
Q

How do oral phosphate binders work?

A

Bind to dietary phosphates and inhibit their absorption

23
Q

What is a nonabsorbable cationic ion-exchange resin that binds intestinal phosphates?

A

Sevelamer

24
Q

What is sevelamer used for?

A

Hyperphosphatemia in chronic kidney disease patients

25
Q

What is common in secondary hyperparathyroidism?

A

Low Vitamin D

26
Q

What are 2 vitamin D analogues that can be used?

A
  1. Calcitriol: Dihydroxylated form of vitamin D3

2. Paricalcitol: Analogue of vitamin D2

27
Q

What category of drug is pamidronate, alendronate, risedronate ibandronate, zolendronate?

A

Bisphosphonates

28
Q

What is the MOA of bisphosphonates?

A

Substitute for pyrophosphate…instead of a hydrolyzable P-O-P bond, these have a non-hydrolyzable P-C-P bond

29
Q

What does the non-hydrolyzable P-C-P bond in bisphosphonates result in?

A

Retards formation and dissolution of hydroxyapatite crystals in and out of bone–> Inhibit bone resportion

30
Q

What is the absorption and half-life of bisphosphonates like?

A

Poor GI absorption, long half lives

31
Q

What are the 2 benefits of bisphosphonates?

A
  1. Greatest increase in BMD

2. Decreased vertebral fractures: Etidronate and ibandronate

32
Q

Can bisphosphonates be used in pregnancy?

A

CAUTION

33
Q

What are some adverse effects of bisphosphonates?

A

Esophageal ulcer, esophageal stricture, dyspepsia, dysphagia, acid regurgitation, abdominal pain, nausea, diarrhea, musculoskeletal pain

34
Q

What adverse effect is associated with long-term therapy of etidronate?

A

Osteomalacia

35
Q

What are alandronate and risedronate?

A

Bisphosphonates

36
Q

What are 2 indications of alandronate and risedronate?

A

Prevention and treatment of

  1. Postmenopausal osteoporosis
  2. Glucocoticoid-induced osteoporosis
37
Q

What is calcitonin?

A

Physiologica antagonist of PTH

38
Q

What does calcitonin do?

A

Inhibits osteoclast action

39
Q

What are 2 beneficial effects of calcitonin?

A

Increased BMD, decreased vertebral fracture

40
Q

What are 2 indications for calcitonin?

A
  1. Treatment of osteoporosis in women who are at least 5 or more years postmenopausal
  2. Pagent disease
41
Q

What is seen in Pagent disease and why is calcitonin effective?

A

Pagent disease has greatly accelerated osteoclastic activity and here calcitonin reduces calcium resportion

42
Q

What are 3 adverse effects of the nasal formulation of calcitonin?

A
  1. Rhinitis, nasal irritation, nasal dryness
  2. Pain, arthralgia
  3. Headache
43
Q

What is an estrogen agonist that is approved for the prevention of osteoporosis?

A

Raloxifene

44
Q

How does raloxifene work?

A

It decreases bone reabsorption and bone turnover

45
Q

What are 2 advantages of raloxifene?

A

It doesn’t stimulate the endometrium and it decreases LDL and total cholesterol

46
Q

What are 3 adverse effects of raloxifene?

A
  1. Hot flashes
  2. Venous thromboembolism
  3. Peripheral edema and leg gramps
47
Q

What are 4 things estrogen can do?

A
  1. Stabilizes bone remodeling
  2. Increase GI Ca absorption
  3. Promote calcitonin synthesis
  4. Increases number of Vitamin D receptors on osteoblasts
48
Q

True or False: Estrogen acts on osteoblasts and osteoclasts?

A

TRUE

49
Q

What are the effects of estrogen as far as bones go?

A

Increased BMD, decreased vertebral, non-vertebral, and hip fractures

50
Q

With regards to cholesterol, what are the effects of estrogens?

A

Decrease LDL and lipoprotein, increase HDL and triglycerides

51
Q

What are 3 things estrogen can relieve?

A

Hot flashes, sweating arthralgia, and myalgias (menopausal symptoms)

52
Q

What are 2 disadvantages of estrogen?

A
  1. Increased risk of endometrial hyperplagia and endometrial cancer
  2. May increase risk of breast cancer
53
Q

What can calcium decrease the absorption of (2)?

A
  1. Tetracyclines

2. Quinolones

54
Q

What are 2 important contraindications of bisphosphonates?

A
  1. Hypocalcemia: Other bone and mineral metabolism disturbances
  2. Severe renal impairment

Endrocrine Exam 2 (7 decks)

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