Calcium Homeostasis (Welch) Flashcards
1
Q
What is a SERM?
A
Selective Estrogen Receptor Modulation
2
Q
What are 3 common SERMs?
A
- Tamoxifen
- Raloxifene
- Clomiphene
3
Q
Tamoxifen, Raloxifene, and Clomiphene exert their effects how?
A
Competetive partial agonist inhibitor of estradiol at the estrogen receptor
4
Q
What are 2 indications for Tamoxifen (a SERM)?
A
“Palliative treatment of breast cancer in post menopausal women”
“Chemoprevention of breast cancer in high risk women”
5
Q
Of the SERMs Tamoxifen, Raloxifene, and Clomiphene, which ones increase bone density?
A
- Tamoxifene
2. Raloxifene
6
Q
Of the SERMs Tamoxifen, Raloxifene , and Clomiphene, which ones increase ovulation?
A
- Clomiphene
2. Tamoxifene
7
Q
Of the SERMs Tamoxifen, Raloxifene , and Clomiphene, which ones have an effect on mammary cell proliferation?
A
None
8
Q
Of the SERMs Tamoxifen, Raloxifene , and Clomiphene, which ones increase uterine cell proliferation?
A
Tamoxifene
9
Q
What is the only thing that Raloxifene (a SERM) stimulates in women?
A
Bone density
10
Q
What is the only thing that Clomiphene (a SERM) stimulates in women(?
A
Ovulation
11
Q
What are the three things Tamoxifen (a SERM) stimulates in women?
A
- Ovulation
- Uterine cell proliferation
- Bone density
12
Q
What is the one thing that Tamoxifen (a SERM) interrupts in women?
A
Mammary cell proliferation
13
Q
What are the 3 things Raloxifene (a SERM) interrupts in women?
A
- Ovulation
- Mammary cell proliferation
- Uterine cell proliferation
14
Q
Why is Clomiphene (a SERM) both estrogenic and anti-estrogenic?
A
it is estrogenic because it stimulates pituitary release of LH and FSH that increase ovulation
15
Q
Evista is the brand name for what SERM?
A
Raloxifene
16
Q
Raloxifene protects against what fractures related to osteoporosis?
A
- Spine fractures
2. Not protective against hip fractures
17
Q
What is an increased risk when taking Raloxifene?
A
Thrombophlebitis
18
Q
What are 2 osteoporosis drugs that do prevent both spine and hip fractures?
A
- Bisphosphonates
2. Teriparatide
19
Q
What are 2 physiologic functions of Parathyroid hormone (PTH)?
A
- Maintains calcium levels in extracellular fluid
2. Maintains integrity of parathyroid gland
20
Q
If PTH maintains extracellular Calcium levels, by default what is it also maintaining?
A
Intracellular calcium levels
21
Q
If the level of extracellular Calcium decreases, what is released by what?
A
PTH released by parathyroid gland to increase extracellular calcium
22
Q
What hormone opposes PTH?
A
Calcitonin from the C-cells of the thyroid
23
Q
What is the major source for PTH to harvest Calcium to increase the extracellular calcium levels?
A
Bone
24
Q
What 2 things are released when PTH acts on bone?
A
- Calcium ions (Ca++)
2. Phosphate (PO4)
25
What are Primary, Secondary, and Tertiary sources for PTH to increase Calcium?
```
Primary = bone
Secondary = intestine
Tertiary = kidney
```
26
How does PTH get calcium from the kidney?
Resorb calcium and excrete Phosphate
27
What will result if pt has excess PTH with respect to the kidney?
Patient will no longer excrete phosphate (PO4) and calcium will not be resorbed causing a calcium phosphate kidney stone
28
What is a lab value to check for a patient with kidney stones?
PTH level
29
What are 2 causes of Hypoparathyroidism?
1. Iatrogenic (surgery, most common)
| 2. Parathyroid gland disease
30
A person having tetany, muscle spasms, generalized convulsions, possible respiratory failure causing death could have what condition and why?
Hypoparathyroidism, no enough Calcium to control muscle contractions
31
Can PTH be given directly to treat hypoparathyroidism?
No, it is a peptide and very expensive
32
What is the treatment for hypoparathyroidism?
Vitamin D and Calcium supplement of the diet
33
What is the synthetic form of human PTH?
Forteo. Recombinant human PTH 1,34 (teriparatide)
34
When would Forteo (rhPTH 1,34) be indicated?
Hyperparathyroidism
35
What do chronically high levels of PTH cause?
increased osteoclast activity
36
What would intermittent administration of rhPTH1,34 do?
Stimulate osteoblastic activity when given intermittently. The key is the intermittent administration of rhPTH 1,34.
37
What are 2 causes of primary hyperparathyroidism?
1. Parathyroid hyperplasia
| 2. Adenoma
38
Hypercalcemia caused by hyperparathyroidism produces what symptoms?
1. Muscle weakness
| 2. Smooth m. dysfunction causing constipation, flatulence, anorexia, nausea, vomiting
39
What are 2 renal symptoms associated with Primary hyperparathyroidism?
1. Hypercalciuria
2. Hyperphosphaturia
(Both lead to kidney stones and calcified nephrons)
40
What is the treatment for Primary Hyperparathyroidism?
Surgery
41
A patient with kidney stones, calcified nephrons, and profound osteoporosis would likely have?
Primary hyperparathyroidism
42
A malabsorption syndrome or renal disease, either one causing low plasma calcium that leads to an increased secretion of PTH is what?
Secondary hyperparathyroidism
43
What will be the only clinical symptom of secondary hyperparathyroidism?
Decalcification of bone
44
What clinical symtoms differ primary hyperparathyroidism from secondary hyperparathyroidism?
Secondary has no hypercalciuria or hypercalcemia
45
What is the treatment for secondary hyperparathyroidism?
Treat underlying renal or malabsorption disorder
46
What hormone is secreted by the parafollicular C- cells of the thyroid and has the physiologic function of lowering plasma Calcium ion levels (antagonist of PTH)?
Calcitonin
47
What stimulates release of Calcitonin?
High plasma calcium levels (PTH would be inhibited)
48
What inhibits release of calcitonin?
Low calcium levels (PTH would be released)
49
What is the mechanism of action of calcitonin?
Inhibits bone resorption by opposing action of PTH
50
What are 3 therapeutic uses for calcitonin?
1. Lower hypercalcemia in hyperparathyroidism, idiopathic hypercalcemia, and Vitamin D intoxation
2. Postmenopausal osteoporosis
3. Paget’s disease
51
What are 2 major uses for calcitonin in the U.S.?
1. Paget's disease
| 2. Osteoporosis
52
What are 3 preparations of Calcitonin for the treatment of hypercalcemia, postmenopausal osteoporosis, or Paget’s disease?
1. Miacalcin
2. Calcimar
3. Cibacalcin
53
What are 3 side effects of Calcitonin treatment?
1. Nausea
2. Inflammation at injection site
3. Flushing
54
Where are the majority of osteoporosis related fractures?
Vertebral fractures
55
What are 8 drugs associated with the development of osteoporosis?
1. Corticosteroids
2. Thyroid hormone
3. Anticonvulsant
4. Aluminum antacids
5. Heparin
6. Cancer chemotherapy
7. Tetracycline
8. Isoniazid (Tb antibiotic)
56
What are 10 diseases that can predispose to osteoporosis?
1. Hyperthyroidism
2. Hyperparathyroidism
3. Paralysis
4, Chronic obstructive lung disease
5. Intestinal malabsorption
6. Renal dysfunction
7. Malignancy
8. Diabetes mellitus
9. Pregnancy
10. Rheumatoid arthritis
57
What are 3 strategies for management of osteoporosis?
1. Prevent it
2. Detect it and treat early to decrease progression
3. Limit disability and provide rehab
58
What are 3 treatment modalities for Osteoporosis?
1. Calcium supplementation
2. Salmon calcitonin
3. Estrogens
59
What is required for calcium absorption and bone mineralization?
Vitamin D
60
What is the starting point for Vit D in the body?
7-dehydrocholesterol conversion to cholecalciferol by UV light on the skin
61
What is an Inactive form of Vit D?
Cholecalciferol
62
What is the active form of Vitamin D?
1,25 dihydroxycholecalciferol
63
Where does cholecalciferol get hydroxylized to its active form?
1. C-25 hydroxylized in liver
2. C-1 hydroxylized in kidney
3. Kidney hydroxylization is final step
64
What therapy is FDA approved for the prevention of osteoporosis, but the woman must be informed of the inherent risk of using it?
Estrogen therapy
65
What ist he mechanism of action for estrogen therapy to prevent osteoporosis?
Decrease osteoclast activity
66
Does estrogen just decrease fracture risk of osteoporosis?
No, also increases bone density by 1-5%
67
What is a disadvantage of estrogen therapy?
Discontinuing will accelerate bone loss
68
What is a Selective Estrogen Receptor Modulator (SERM) that is used to treat and prevent osteoporosis?
Raloxifene (Evista)
69
What effects does Raloxifene (Evista, a SERM) have on bone?
Estrogenic effect on bone (decrease osteoclastic activity)
70
What effect does Raloxifene (Evista, a SERM) have on breasts and endometrium?
Antiestrogenic effect
71
By how much does Raloxifene (Evista, a SERM) increase bone density?
2%
72
Raloxifene (Evista, a SERM) decreases the risk of what fracture type?
Vertebral fracture (by 30-40%)
73
Can Raloxifene (Evista, a SERM) be used to treat or prevent osteoporosis in men?
No
74
What is an osteoporosis treatment that works by mimicking a normal structural component of the bone and get into Osteoclast DNA and cause osteoclast apoptosis?
Bisphosphonates
75
What is the risk associated with bisphosphonates?
Stay in bone for a long time because they mimic bone components
76
What are 2 approved bisphosphonates?
1. Alendronate (Fosamax)
| 2. Ridedronate (Actonel)
77
What are 3 indications for bisphosphonate use?
1. Prevention and treatment of osteoporosis
2. Steroid induced osteoporosis treatment
3. Paget's disease treatment
78
Risendronate (Actonel) is also approved for what?
Increase bone mass in men
79
Where do bisphosphonates bind to inhibiti osteoclast function?
Bind to hydroxyapatite at sites of active bone resorption
80
What is increased with increased duration of taking a bisphosphonate?
BONJ
81
What are 4 bisphosphonates Dr Welch listed?
1. Alendronate (can treat men, women, glucocorticoid-induced, and Paget’s)
2. Risendronate (can treat women, glucocorticoid- induced, and Paget’s)
3. Pamidronate
4. Zoledronic acid
82
What would chronic application of rhPTH 1,34 (Forteo PTH pen) do?
Activate osteoclasts and break down bone
83
What would intermittent application of rhPTH 1,34 (Forteo PTH pen) do?
Stimulate osteoblasts and build bone
84
Forteo (rhPTH 1,34) can be used to treat what pt types?
1. Postmenopause osteoporosis
2. Men w/idiopathic or hypogonadal osteoporosis 3. Men who can’t tolerate other osteoporosis therapy Pt w/ low bone density(T-score <3)
4. Patient w/ fractures and on other osteoporosis therapy
5. Patient who cannot tolerate oral bisphosphonate therapy
85
Who should not be given Forteo?
1. Patient w/ Paget’s disease (their PTH is already high)
2. Patient w/ open epiphyses (puberty/adolescents)
3. History of irradiation of the skeleton
4. Undefined increase in bone alkaline phosphotase
86
What is the result of the abnormal Growth hormone of Paget’s causing increased bone growth potential as well as PTH breaking down bone while Calcitonin building bone up?
Poorly formed bones
87
What is the demographic of Paget’s disease?
Patient over 40 years old
88
What causes the bone lesions of Paget's disease?
Increased bone resorption followed by a period of increased bone formation
89
What are 3 treatments for Paget's disease?
1. Antibiotic
2. Calcitonin
3. Palmidronate (bisphosphonate = inhibit bone resorption)
90
A patient with the following symptoms would have what disease: headache, hearing loss, increased head size, bowing of limbs, curvature of spine, hip pain?
Paget's disease
91
What are 3 things that can be used to diagnose Paget's disease?
1. Serum alkaline phosphatase
2. X-rays
3. Bone scans
92
What is the drug of choice for Paget's disease treatment?
Bisphosphonates
93
Because Paget’s and osteoporosis can be treated with bisphosphonates are they dosed the same and treated for the same duration?
No. Paget’s is done 4/day for 6 months (increased dose for shorter duration). Osteoporosis is 1/week for 2 years (lower dose for longer duration)
94
What is an alternate therapy for Paget’s should the bisphosphonate not be tolerated ?
Calcitonin
95
What drug is contraindicated in Paget's disease?
rhPTH 1,34 (Fortea)
96
What are hearing loss and headaches common in Paget's?
Elongated skull stretches nerves
97
What are 7 complications of Paget's disease?
1. Neural compression
2. Fractures
3. Sarcoma
4. Gout
5. Hypercalcuria
6. Kidney stones
7. Heart failure
98
Of the complications of Paget's Disease, which two are due to increased PTH?
1. Hyperalcuria
| 2. Kidney stones
