Pharmacology of Parathyroids and Bone Flashcards Preview

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Flashcards in Pharmacology of Parathyroids and Bone Deck (63)
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1
Q
What type of bone is in the shafts of long bones? vertebral bodies, ribs, pelvis and ends of long bones?
A
-shafts-cortical
-vertebral bodies, ribs, pelvis and ends of long bones-trabecular
2
Q
What are the 3 main cell types in bone and what is their function?
A
-osteoblasts-bone forming cells
-osteoclasts-bon resorption
-osteocytes-communication and mobilization
3
Q
What are the 2 types of matrix in bone and what are they made up of?
A
organic-type 1 collagen and proteins
inorganic-hydroxyapatite
4
Q
What controls the secretion of PTH?
A
-ionized calcium (when low PTH is stimulated)
5
Q
Which 2 organs does PTH directly effect?
A
-bone-releases Ca from bone (activates osteoblasts which activate osteoclasts-->according to pathoma)
-Kidney-reabsorbtion of Ca and production of Vitamin D which leads to absorbtion of Ca and PO4 in small intestine
***All lead to increased serum Ca levels***
6
Q
What are the 3 forms of Ca in the circulation and which are the most important physiologically?
A
1) Ionized Ca
2) protein bound Ca
3) Complexed to bicarb, citrate or phos
**Ionized and free more important physiologically**
7
Q
Changes in which protein in the blood can affect the measurement of calcium?
A
albumin
8
Q
What is the equation to correct Ca based on albumin levels?
A
corrected Ca= measured Ca+.8 X (4-measured albumin)
9
Q
What 3 things can increase PT reabsorbtion of Phosphorous?
A
-phosphate depletion
-hypoparathyroidism
-hypocalcemia
10
Q
What increased Phosphate excretion?
A
-PTH
-PTHrp
-hypercalcemia
-hypokalemia
-hypomagnesemia
-calcitonin
-glucocorticoids
-diuretics
11
Q
What is magnesium necessary for?
A
the release of PTH and the action of PTH on its target tissues
12
Q
Where is Vitamin D made? Where do it's 2 hydroxylations occur? How does it maintain normal serum Ca level?
A
-made in the skin
-hydroxylations in the liver and kidney
-mantains Ca by increasing absorption of dietary Ca and stimulating bone cells to become osteoclasts
13
Q
If a patient has hypercalcemia and their PTH level is not suppressed (high or normal) what do they most likely have?
A
primary hyperparathyroidism-excessive secretion of PTH from parathyroid glands (usually in 6th decade of life)
14
Q
If a patient has hypercalcemia and their PTH level is low, what other tests should be ordered in order to make a dx?
A
-PTHrp, Vitamin D, and 24 hour urine calcium
15
Q
What would the lab values of Ca, PTH, Phosphorous and Urine calcium be like in primary hyperparathyroidism?
A
-Ca high
-PTH high or normal
-Phosphorous low
-Urine calcium high
16
Q
What are some of symptoms of primary hyperparathyroidism?
A
lethargy
drowsiness
stupor
coma
proximal muscle weakness
hyporeflexia
N/V
pancreatitis
Polyuria
Polydipsia
Nephrocalcinosis
Nephrolithiasis
HTN
Short QT
bradycardia
increased sensitivity to digitalis
17
Q
How is primary hyperparathyroidism usually treated?
A
Surgery to remove abnormal tissue
(if disease is mild or asymptomatic they could be followed)
18
Q
What medications can be used to medically treat hyperparathyroidism?
A
-Bisphosphonates-tx low bone density
-Calcimimetics: to reduce PTH and Ca levels by altering fxn of Ca sensing receptor
-Sensipar (Cinacalcet): for hyperparathyroidism in renal disease and parathyroid carcinoma or in pts who refuse surgery
19
Q
What are some other causes of hypercalcemia aside from hyperparathyroidism?
A
-malignancy
-Familial hypocalciuric hypercalcemia-PTH is normal or slightly high
-milk alkali syndrome-excessive OTC Ca use
-Granulomatous Diseases-can increase Vit D levels
-Medications: thiazides and Lithium
20
Q
What are the 3 general ways to decrease serum Ca?
A
-expand volume
-increase urine Ca excretion
-inhibit bone resorption
21
Q
How is mild hypercalcemia treated? (Ca<12)
A
increase fluid intake
moderate Ca in diet
avoid certain meds
22
Q
What are the 5 main treatments for hypercalcemia?
A
-fluids-possible need for loop diuretic after to increase Ca excretion and prevent volume overload
-Bisphosphonates
-calcitonin
-corticosteroids
-Dialysis
23
Q
What is the mechanism of Biphosphonates and what are the 2 most commonly used?
A
-inhibits bone resorption
-Pamidronate and Zoledronic Acid
***Not effective immediately***
24
Q
What is mechanism of calcitonin and what can repeated exposure lead to, making it most useful in the acute setting?
A
-rapid lowering of Ca by increasing urinary Ca excretion and inhibiting bone resorption
-repeated exposure can lead to downreg of calcitonin receptors-->tachyphylaxis in 2-3 days
**lowers Ca 1-2mg/dl within 2-4 hours-->Thus used for SEVERE Hypercalcemia**
25
Q
What is the mechanism of corticosteroids in the treatment of hypercalcemia?
A
-decreases production of Vitamin D
**Used in Vit D intoxication, granulomatous diseases and hematologic malignancies**
26
Q
When is dialysis used for treatment of Hypercalcemia?
A
-in pts with renal failure or when there is no response to other treatments
27
Q
What is secondary hyperparathyroidism? What is the mechanism of this in renal disease?
A
-PTH secreted in response to perceived low Ca
(Ca is actually low or normal)
-Renal disease- from phosphate retention and deficient Vit D
**Phosphate directly stimulates PTH secretion at high levels**
28
Q
How is secondary hyperparathyroidism from renal disease treated?
A
-low phosphate diet
-phosphate binders
-replacement of Vitamin D
-Calcimimetics
-Dialysis
29
Q
What is tertiary hyperparathyroidism?
A
-parathyroid glands become autonomous after prolonged secondary hyperparathyroidism
**Serum Ca is elevated**
30
Q
What causes hypocalcemia?
A
-destruction or failure of parathyroid glands
-inactivity of PTH at target tissues
31
Q
What are some symptoms of hypocalcemia?
A
paresthesias
bronchospasm
laryngospasm
tetany
seizures
increased ICP with papilledema
Prolonged QT
Heart block
CHF
Cataracts
32
Q
What else should be checked when a low serum Ca is obtained?
A
ALBUMIN!!
(could also check Mg, phosphorous and creatinine levels)
33
Q
What do the lab values of Ca, Phosphorous, PTH and Creatinine look like in Secondary hyperparathyroidism due to chronic renal failure?
A
-Ca-low
-Phosphorous-high
-PTH-high
-Creatinine-high
34
Q
How does the low excretion of phosphorous and low Vit D in Secondary hyperparathyroidism due to chronic renal failure lead to hypocalcemia?
A
-decreased Ca absorption from the gut
-decreased Ca mobilization from the bone-->PTH secretion
35
Q
What are the 3 phosphate binders used to treat Secondary hyperparathyroidism due to chronic renal failure?
A
-calcium carbonate
-calcium acetate
-sevelamer (renagel)
36
Q
What are the 2 Vitamin D analogs used to treat Secondary hyperparathyroidism due to chronic renal failure?
A
-calcitriol
-doxercalciferol
37
Q
What is hypoparathyroidism?
A
PTH produced is insufficient to maintain serum Ca levels or unable to fxn at target tissues
38
Q
What would the Ca, phophorous and PTH levels be like in hypoparathryoidism? What is different in pseudohypoparathyroidism?
A
-Ca low
-Phosphorous high
-PTH low
**In pseudohypoparathyroidism PTH is high**
39
Q
How is hypoparathyroidism treated?
A
-Oral Ca and Vitamin D
-normalize Ca and Phosphorous levels without causing hypercalciuria
**Phosphate restricted diet w/ Ca goals on low end of normal**
40
Q
How might Vitamin D deficiency present?
A
-low Ca and Phosphorous
-high PTH
-low urine Ca
41
Q
Which form of Vitamin D is more efficacious; cholecalciferol or ergocalciferol?
A
cholecalciferol
42
Q
How is acute hypocalcemia treated?
A
-tx depends on severity
-Ca gluconate diluted in D5W or NS IV
-Possibly add oral Vitamin D
-If hypocalcemia is persistent tx with supplemental Ca every 6-12 hours
43
Q
What are some causes of hypophosphatemia?
A
-decreased intestinal absorption-Vitamin D important for promoting this!!
-increased urinary losses
-transcellular shift
**lack of VitD may result in rickets or osteomalacia**
44
Q
How are X-Linked and AD hypophosphatemic rickets characterized?
A
low phosphorous-decreased reabsorption from renal tubule
-decreased absorption of Ca and phosphorous from intestines
-Varying degree of bone involvement
45
Q
How is hypophosphatemia treated?
A
-replacing phosphorous
-calcitriol
46
Q
What is osteoporosis? How is more susceptible?
A
-low bone mass, increase in bone fragility
-Women are more susceptible postmenopausal
-Men more likely to have secondary underlying cause
47
Q
Why does bone loss occur in the post menopausal state?
A
-increase in rate of bone remodeling
-imbalance in the activity of osteoblasts and osteoclasts
48
Q
What is a normal T score?
A
greater than -1
(-1 to -2=osteopenia, less than -2.5= osteoporosis)
49
Q
What is the mechanism of bisphosphonates and which ones are currently approved for osteoporosis treatment?
A
-reduce osteoclast bone resorption and increase BMD, decreased fracture risk
-Alendronate, risedronate, and ibandronate
50
Q
What are the restrictions when taking bisphosphonates?
A
Need to be taken:
-fasting
-in the morning
-with full glass of water
-remain upright for atleast 30 mins
-no eating or taking other meds during that time
**Side effects-local GI irritation**
51
Q
If the Gi side effects are too much for a pt with osteoporosis what can be done?
A
Zoledronate-IV once a year
Boniva IV every 3 months
52
Q
What is the mechanism of action of SERM's in the treatment of osteoporosis?
A
-used in postmenopausal women
-estrogen like compounds that decrease bone resorption (selective to bone)
53
Q
What are the 3 SERM's?
A
Raloxifene (risk of DVT and hot flashes)
basedoxifene
lasofoxifene
54
Q
Where is Calcitonin usually secreted from and what does it do?
A
-secreted by C-cells in thyroid
-inhibits osteoclast resorption
**nasal preparation (salmon calcitronin) used in osteoporosis, can cause rhinitis**
55
Q
What is one unique effect of salmon calcitronin?
A
has an analgesic effect on acute vertebral fractures
56
Q
What is Teriparatide and what pts is it reserved for?
A
-PTH analog
-pts at high risk of fracture or who couldn't tolerate or have failed other therapies
57
Q
What are some side effects of Teriparatide and what is it's black box warning?
A
SE-dizziness, palpitations, transient hypercalcemia
BB-osteosarcoma in rats
58
Q
What is Denosumab and what are some possible side effects?
A
-RANK Ligand inhibitor-antiresorptive (SQ injection every 6 months)
-SE-skin infections, hypocalcemia-especially in those with low GFR
59
Q
What are some possible future treatments for osteoporosis?
A
-other anabolic agents
-Cathepsin K inhibitors
-Sclerostin pathway
60
Q
What is Paget's disease of bone?
A
-localized disorder of bone remodeling-from increase in osteoclast mediated bone resorption--->disorganixed bone at 1+ sites
61
Q
What are some typical sites for Pagets disease of bone and how is it usually found?
A
-pelvis, femur, skull, spine and tibia
-usually asymptomatic and found on x-ray
62
Q
What are some possible complications of pagets disease of bone?
A
-hearing loss
-fractures
-increased bleeding risk if surgery performed on untreated pagets bone
-osteosarcoma
63
Q
What are the 2 main categories of medications used to treat Pagets disease of bone?
A
-Bisphosphonates: Pamidronate (IV), Alendronate, Risedronate, and Zoledronate
-Calcitonin