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1 Calcium Drugs
Scammell
97
Pharmacology
Graduate
04/17/2010

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Cards

Term
Ca homeostasis in the body includes tight regulation of what type of Ca?
Definition
Both extra and intracellular Ca
Term
Plasma levels of Ca?
Definition
2.5 mM
Term
Cytoplasmic levels of Ca?
Definition
100 nM
Term
What 3 locations in the body exchange Ca?
Definition
1. Intestine
2. Bone
3. Kidney
Term
How is Ca exchange in various tissues regulated?
Definition
Hormonally
Term
How much Ca should be taken in per day?
Definition
About 1200 mg/day
Term
The amount of Ca absorbed from the intestines depends on what?
Definition
Levels of vitamin D
Term
How much Ca exchange take place in the kidneys?
Definition
A large amount of Ca is filtered and almost as much is reabsorbed
Term
Regulation of Ca homeostasis is through what 2 things?
Definition
1. Hormones
2. Drugs
Term
Intestinal absorption of Ca is stimulated by what hormone?
Definition
Vitamin D
Term
Intestinal absorption of Ca is inhibited by what hormone?
Definition
Glucocorticoids
Term
Renal absorption of Ca is stimulated by what hormone?
Definition
Parathyroid hormone (PTH)
Term
Effect of thiazide diuretics on Ca clearance?
Definition
Decrease

Can result in hypercalcemia
Term
Effect of loop diuretics on Ca clearance?
Definition
Increase

Can result in hypocalcemia
Term
What type of diuretics increase Ca clearance?
Definition
Loop
Term
What type of diuretics decrease Ca clearance?
Definition
Thiazide
Term
Bone resorption of Ca is stimulated by what hormone?
Definition
Parathyroid hormone (PTH)
Term
Bone resorption of Ca is inhibited by what hormones (2)?
Definition
Calcitonin and estrogen
Term
Intestinal absorption of Ca is ____ process that takes place where?
Definition
An active process

In the proximal small intestine
Term
Renal absorption of Ca is ____ process that takes place where?
Definition
Active process

In the proximal tubule
Term
What cells are responsible bone resorption?
Definition
Osteoclasts
Term
What cells are responsible for bone mineralization/formation?
Definition
Osteoblasts
Term
Bone mineralization/formation is stimulated by what?
Definition
1. Sodium fluoride
2. Calcium
3. Teraparatide
Term
When is PTH secreted from the parathyroid gland?
Definition
When plasma Ca levels get too low
Term
What are the 3 effects of PTH?
Definition
1. Bone – stimulate resorption from bone
2. Kidney – stimulate reabsorption in the proximal tubule
3. Intestine – stimulates the final step in the activation of vitamin D
Term
What stimulates release of calcitonin from the C cells of the thyroid gland?
Definition
High plasma Ca levels
Term
What cells secrete calcitonin when plasma levels of Ca get too high?
Definition
C cells of the thyroid
Term
Effect of calcitonin?
Definition
Decrease osteoclastic activity on bone and decrease plasma Ca
Term
Structure of PTH?
Definition
84 amino acid peptide
Term
Release of PTH is stimulated by what?
Definition
Low Ca
Term
Effect of PTH?
Definition
1. Increases renal absorption of Ca
2. Increases osteoclastic activity
3. Activates vitamin D

All act to increase Ca in plasma
Term
Structure of calcitonin?
Definition
32 amino acid peptide in parafollicular cells
Term
Release of calcitonin is stimulated by what?
Definition
High Ca
Term
Effect of calcitonin?
Definition
Inhibits osteoclastic activity

Decreases Ca in plasma
Term
Vitamin D activation is stimulated by what?
Definition
Sunlight/UV light
Term
The final conversion to the active form of vitamin D takes place where?
Definition
Kidney
Term
Effect of vitamin D?
Definition
1. Increases intestinal absorption of Ca
2. Increases bone mineralization
Term
Effect of estrogen in Ca homeostasis?
Definition
Reduces PTH action on bone
Term
Effect of corticosteroids in Ca homeostasis?
Definition
Inhibits action of vitamin D in intestine
Term
What are the 5 clinical manifestations of hypercalcemia?
Definition
1. General malaise
2. Loss of memory
3. Anorexia
4. Nausea
5. Polyuria
Term
What are some causes of hypercalcemia?
Definition
1. Neoplasms
2. Hyperparathyroidism
3. Non-parathyroid endocrinopathy
4. Toxicities – vitamin A/D
5. Increased production or sensitivity to vitamin D
6. Dehydration with hyperproteinemia
7. Immobilization with underlying bone resorptive disorder
8. Acute renal failure with rhabdomyolysis
Term
What are the 6 types of treatment for hypercalcemia?
Definition
1. Saline diuresis
2. Loop diuretics
3. Calcitonin
4. Corticosteroids
5. Gallium nitrate
6. Bisphosphonates
Term
How does saline diuresis treat hypercalcemia?
Definition
Promotes volume expansion acutely
Term
How do loop diuretics treat hypercalcemia?

What is an example?
Definition
Increase Ca clearance by the kidney

Furosemide
Term
How is calcitonin used in treatment of hypercalcemia?
Definition
Chronically

Secreted by C cells of the thyroid and decreases osteoclastic activity
Term
What are the 2 forms of calcitonin?
Definition
1. Human
2. Salmon – 2x more potent in humans
Term
What type of hormone is calcitonin?
Definition
Peptide
Term
Is calcitonin orally active?
Definition
NO
Term
Administration of calcitonin
Definition
Has to be taken by intranasal preparations because it is a peptide and therefore not orally active
Term
Why is calcitonin not useful long term?
Definition
Ab are made to salmon calcitonin which decreases its effectiveness

Also vitamin D an PTH are more important for long term Ca homeostasis/regulation in the body
Term
How do corticosteroids treat hypercalcemia?
Definition
Inhibit Ca absorption from the gut
Term
What is given for vitamin D toxicity and why?
Definition
Corticosteroids

Antagonize the effects of vitamin D in the intestine
Term
How does gallium nitrate treat hypercalcemia?
Definition
Inhibits osteoclastic activity
Term
What drug that inhibits osteoclastic activity is approved for the treatment of hypercalcemia?
Definition
Gallium nitrate
Term
What are 3 bisphosphonates?
Definition
1. Alendronate
2. Pamidronate
3. Zoledronate
Term
What do all bisphosphonates end with?
Definition
-dronate
Term
How do bisphosphonates treat hypercalcemia?
Definition
Inhibit osteoclastic activity
Term
What are 2 causes of hypocalcemia?
Definition
1. Hypoparathyroidism
2. Vitamin D deficiency
Term
What are the clinical manifestations of hypocalcemia?
Definition
1. Tetany
2. Convulsions
3. Muscle cramps
Term
What are 2 ways to treat hypocalcemia?
Definition
1. Calcium salts
2. Vitamin D
Term
2 examples of calcium salts?
Definition
Calcium gluconate or calcium chloride
Term
Administration of Ca salts?
Definition
IV
Term
When are calcium salts given for treatment of hypocalcemia?
Definition
Acutely
Term
What is given following IV infusion of Ca salts for the treatment of hypocalcemia?
Definition
Oral Ca salts – calcium carbonate
Term
How does vitamin D treat hypocalcemia?
Definition
Increases Ca absorption by the small intestine
Term
What is the shortest acting vitamin D agent?
Definition
Calcitriol
Term
what forms of vitamin D can be given in treatment of hypocalcemia?
Definition
1. Calcitriol
2. Hydroxyl-vitamin D3
3. Plant steroid with vitamin D activity
Term
What is Paget’s disease?
Definition
Disordered bone remodeling due to increased numbers and activity of osteoclasts
Term
What are the characteristics of Paget’s disease?
Definition
Weak bones, arthritis, deafness, elevated serum alkaline phosphatase
Term
What 2 drug types are used in the treatment of Paget’s disease?
Definition
1. Calcitonin
2. *Bisphosphonates such as alendronate
Term
Why is calcitonin only used intermittently to treat Paget’s disease?
Definition
Because resistance builds up due to Abs and because PTH/vitamin D are more important hormones
Term
Administration of calcitonin?
Definition
Intranasal
Term
What bisphosphonate is used to treat Paget’s disease?
Definition
Alendronate
Term
Bisphosphonates are structurally similar to what compound?
Definition
Pyrophosphate
Term
Bisphosphonates adsorb to what?
Definition
Crystal surface
Term
Bisphosphonates mechanism of action?
Definition
Inhibit osteoclastic activity
Term
Are bisphosphonates absorbed well orally?
Definition
NO
Term
Side effect of bisphosphonates given orally?
Definition
Esophagitis
Term
High doses of bisphosphonates can cause what?
Definition
Jaw osteonecrosis
Term
How is the incidence of esophagitis reduced when taking oral bisphosphonates?
Definition
Oral administration requires standing up and large glasses of water; patient can’t lie down for some time after taking them
Term
Why must oral bisphosphonates be taken standing up and with large glasses of water?
Definition
To reduce the incidence of esophagitis
Term
Bisphosphonates use?
Definition
Hypercalcemia, Paget’s disease, osteoporosis
Term
What is osteoporosis?
Definition
Reduced bone mass per volume
Term
Who has the highest incidence of osteoporosis?
Definition
White, postmenopausal women
Term
What are the pathogenic factors for osteoporosis?
Definition
1. Negative Ca balance
2. Estrogen deficiency
3. Reduced vitamin D
4. Reduced exercise
5. Slight build
6. Smoking
7. Corticosteroids
Term
What are 6 available drugs for osteoporosis?
Definition
1. Bisphosphonates
2. Raloxifene
3. Low dose estrogen patch
4. Teriparatide
5. Calcitonin
6. Vitamin D and Ca
Term
How often can IV bisphosphonates be given for the treatment of osteoporosis?
Definition
As often as every 2 years
Term
How often can oral bisphosphonates be given for the treatment of osteoporosis?
Definition
Once per month max
Term
What is raloxifene?
Definition
A partial estrogen agonist given as treatment for osteoporosis
Term
How does raloxifene work in the treatment of osteoporosis?
Definition
A partial estrogen agonist that opposes the effect of PTH which normally activates osteoclasts and causes demineralization of bone
Term
How does teriparatide treat osteoporosis?
Definition
Has the first 34 amino acids of PTH but given once a day causes bone formation
Term
Why does teriparatide not cause the same effects as PTH?
Definition
Its given once a day and causes bone formation

Continuous secretion of PTH during the day increases osteoclastic activity and demineralizes bone
Term
How is calcitonin used in the treatment of osteoporosis?
Definition
Intermittently to decrease osteoclastic activity
Term
Why are calcium and vitamin D given together in the treatment of osteoporosis?
Definition
Vitamin D will increase the absorption of the administered Ca from the small intestine
Term
A man receiving prostate cancer treatment (luprolide) with decreased testosterone can be prone to what bone disorder?
Definition
Osteoporosis
Term
What must be considered with a man taking luprolide or any treatment for prostate cancer that will decrease testosterone?
Definition
His risk for developing osteoporosis

Take calcitonin intranasal, supplement with vitamin D, and consider bisphosphonates
Term
Aunt Rose is a postmenopausal woman, who has been encouraged by her gynecologist to take multivitamins containing vitamin D. Vitamin D is beneficial for postmenopausal women because it:

a. Increases the synthesis of an intestinal calcium binding protein
b. Is a potent antioxidant
c. Stimulates PTH secretion
d. Stimulates glucagon secretion
Definition
a. Increases the synthesis of an intestinal calcium binding protein
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