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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?

24
Q

What is sevelamer used for?

A

Hyperphosphatemia in chronic kidney disease patients

25
What is common in secondary hyperparathyroidism?
Low Vitamin D
26
What are 2 vitamin D analogues that can be used?
1. Calcitriol: Dihydroxylated form of vitamin D3 | 2. Paricalcitol: Analogue of vitamin D2
27
What category of drug is pamidronate, alendronate, risedronate ibandronate, zolendronate?
Bisphosphonates
28
What is the MOA of bisphosphonates?
Substitute for pyrophosphate...instead of a hydrolyzable P-O-P bond, these have a non-hydrolyzable P-C-P bond
29
What does the non-hydrolyzable P-C-P bond in bisphosphonates result in?
Retards formation and dissolution of hydroxyapatite crystals in and out of bone--> Inhibit bone resportion
30
What is the absorption and half-life of bisphosphonates like?
Poor GI absorption, long half lives
31
What are the 2 benefits of bisphosphonates?
1. Greatest increase in BMD | 2. Decreased vertebral fractures: Etidronate and ibandronate
32
Can bisphosphonates be used in pregnancy?
CAUTION
33
What are some adverse effects of bisphosphonates?
Esophageal ulcer, esophageal stricture, dyspepsia, dysphagia, acid regurgitation, abdominal pain, nausea, diarrhea, musculoskeletal pain
34
What adverse effect is associated with long-term therapy of etidronate?
Osteomalacia
35
What are alandronate and risedronate?
Bisphosphonates
36
What are 2 indications of alandronate and risedronate?
Prevention and treatment of 1. Postmenopausal osteoporosis 2. Glucocoticoid-induced osteoporosis
37
What is calcitonin?
Physiologica antagonist of PTH
38
What does calcitonin do?
Inhibits osteoclast action
39
What are 2 beneficial effects of calcitonin?
Increased BMD, decreased vertebral fracture
40
What are 2 indications for calcitonin?
1. Treatment of osteoporosis in women who are at least 5 or more years postmenopausal 2. Pagent disease
41
What is seen in Pagent disease and why is calcitonin effective?
Pagent disease has greatly accelerated osteoclastic activity and here calcitonin reduces calcium resportion
42
What are 3 adverse effects of the nasal formulation of calcitonin?
1. Rhinitis, nasal irritation, nasal dryness 2. Pain, arthralgia 3. Headache
43
What is an estrogen agonist that is approved for the prevention of osteoporosis?
Raloxifene
44
How does raloxifene work?
It decreases bone reabsorption and bone turnover
45
What are 2 advantages of raloxifene?
It doesn't stimulate the endometrium and it decreases LDL and total cholesterol
46
What are 3 adverse effects of raloxifene?
1. Hot flashes 2. Venous thromboembolism 3. Peripheral edema and leg gramps
47
What are 4 things estrogen can do?
1. Stabilizes bone remodeling 2. Increase GI Ca absorption 3. Promote calcitonin synthesis 4. Increases number of Vitamin D receptors on osteoblasts
48
True or False: Estrogen acts on osteoblasts and osteoclasts?
TRUE
49
What are the effects of estrogen as far as bones go?
Increased BMD, decreased vertebral, non-vertebral, and hip fractures
50
With regards to cholesterol, what are the effects of estrogens?
Decrease LDL and lipoprotein, increase HDL and triglycerides
51
What are 3 things estrogen can relieve?
Hot flashes, sweating arthralgia, and myalgias (menopausal symptoms)
52
What are 2 disadvantages of estrogen?
1. Increased risk of endometrial hyperplagia and endometrial cancer 2. May increase risk of breast cancer
53
What can calcium decrease the absorption of (2)?
1. Tetracyclines | 2. Quinolones
54
What are 2 important contraindications of bisphosphonates?
1. Hypocalcemia: Other bone and mineral metabolism disturbances 2. Severe renal impairment

Endrocrine Exam 2 (7 decks)

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