Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
76 Cards in this Set
- Front
- Back
|
What are the Primary regulators of calcium and phosphate homeostasis?
|
PTH & Vitamin D
|
|
|
What are the Secondary regulators of calcium and phosphate homeostasis?
|
Calcitonin
Glucocorticoids Estrogens |
|
|
What are the hormonal regulators of bone mineral homeostasis?
|
PTH
Vitamin D Calcitonin Estrogen Glucocorticoids |
|
|
What are the non-hormonal regulators of bone mineral homeostasis?
|
Bisphosphonates
Fluoride Calcimimmetics |
|
|
By what second messenger system does PTH impart its effects?
|
G-protein coupled receptors
Increase cAMP |
|
|
What effect does PTH have in the Kidney?
|
Inhibits Ca excretion
Promotes Phosphate excretion Stim. productio of Vitamin D metabolites |
|
|
What effect does PTH have on Bone?
|
Promotes Bone turnover by increasing activity of both O.CLASTS and O.BLASTS
|
|
|
What is the net effect of continuous high/elevated concentrations of PTH?
|
Increased Bone resporption
Hypercalcemia Hyperphosphatemia |
|
|
What is the net effect of low intermittent doses of PTH?
|
Net increase in bone formation
|
|
|
What is Teriparatide?
|
a recombinant truncated form of PTH
For Parenteral treatment of osteoporosis |
|
|
Net effects of PTH on INTESTINES
|
Indirectly increases calcium and phosphate absorption by increasing vitamin D metabolites
|
|
|
Net effects of PTH on KIDNEY
|
Decreased calcium excretion, increased phosphate excretion
|
|
|
Net effects of PTH on BONE
|
Ca & Phosphate resorption increased by continuous high concentrations.
Low intermittent doses increase bone formation |
|
|
Net effects of PTH on SERUM levels
|
Serum Ca increased
Serum Phosphate decreased |
|
|
Net effects of Active Vit. D on INTESTINE
|
IIncreased Ca and Phosphate absorption
|
|
|
Net effects of Active Vit. D on KIDNEY
|
Increaed resporption of Ca and Phosphate but usu net increase in urinary Ca due to effects in GI Tract and Bone
|
|
|
Net effects of Active Vit. D on BONE
|
Direct effect: Increased Ca and Phosphate Resorption
Indirect effect: Promoting mineralization by increasing the availability of Ca & Phosphate |
|
|
Net effects of Active Vit. D on SERUM levels
|
Serum Ca and Phosphate BOTH increased
|
|
|
What primarily regulates synthesis and secretion of PTH?
|
Serum [Ca]
A drop in free ionized Ca stimulates PTH release |
|
|
What plays a secondary role in regulating PTH secretion?
|
Active metabolites of Vitamin D
Inhibits PTH synthesis |
|
|
What 2 ways can Vitamin D be obtained in the body?
|
1.) Can be synthesized from 7-dehydrocholesterol w/ UV light
2.) Absorbed from the diet in natural form: - Vitamin D3 (cholecalciferol) -or- plant form: - Vitamin D2 (ergocalciferol) |
|
|
In the SKIN, 7-dehydrocholesterol is converted to what?
|
Cholecalciferol
(Vitamin D3) |
|
|
In the LIVER, Cholecalciferol is converted to what, by what enzyme?
|
25-hydroxycholecalciferol
(calcifediol) via 25-hydroxylase |
|
|
In the KIDNEY, 25-hydroxycholecalciferol is converted to what, by what enzyme?
|
1,25-dihydroxycholecalciferol
(calcitriol) via 1-alpha-hydroxylase |
|
|
Renal stimulation of active vitamin D metabolites is stimulated by...
|
PTH
|
|
|
and inhibited by...
|
Phosphate and Vitamin D
|
|
|
How does Vitamin D cause a net increase in Serum conc. of Ca & Phosphate?
|
By Increasing intestinal absorption & bone resorption
& Decreasing Renal Excretion * b/c it has a larger effect on GI than kidney, it increases Urine Calcium |
|
|
Deficiencies in Vitamin D metabolites cause what diseases?
|
Ricketts in growing children
Osteomalacia in adults |
|
|
What are Vitamin D, Vit. D metabolites, and synthetic derivatives used to treat?
|
- Deficiency states
- Nutritional deficiency - Intestinal osteodystrophy - Chronic kidney or Liver disease - Hypoparathyroidism - Nephrotic syndrome - in Combo w/ Ca supplements to prevent and treat Osteoporosis |
|
|
What are topical forms of Vitamin D used for?
|
Psoriasis
& Hyperproliferative skin disorder |
|
|
When would you used an active form of Vitamin D like Calcitriol?
|
For pts with conditions that impair Vit. D activation:
- chronic Kidney disease - Liver disease - Hypoparathyroidism |
|
|
What are the risks of using Calcitriol for secondary hyperparathyroidism due to chronic kidney disease?
|
Good: reduces PTH levels, corrects hypocalcemia & improves bone disease
Bad: Can cause hypercalcemia, & hypercalciuria |
|
|
What are some drugs that pose less risk of hypercalcemia?
|
Doxercalciferol
Paricalcitol Calcipotriene Selectively inhibit PTH formation, while posing less risk of hypercalcemia |
|
|
What is Doxercalciferol?
|
1-alpha-hydroxyvitamin D2
A prodrug that is converted in liver to 1,25-dihydroxyvitamin D2 |
|
|
What are Paricalcitol and Calcipotriene?
|
Analogs of calcitriol
|
|
|
What are Doxercalciferol & Paricalcitol approved for?
|
Treatment of secondary hyperparathyroidism in pts with Chronic Kidney disease
|
|
|
What is Calcipotriene approved for?
|
Topical tx of Psoriasis
|
|
|
Main Toxicity of overdosing with Vitamin D and its analogs
|
Hypercalcemia
Hyperphosphatemia Hypercalciuria |
|
|
Where is calcitonin secreted?
|
By the Thyroid gland
|
|
|
What effects does calcitonin have on Ca and Phosphate?
|
Decreases serum Ca and Phosphate levels
by Inhibiting bone resorption & Inhibiting Renal excretion of both Ca & Phosphate |
|
|
What is calcitonin approved for?
|
Osteoporosis
It has been shown to increase bone mass and to reduce spine fractures, but not as effective as teriparatide or bisphosphonates |
|
|
Where is the Calcitonin that we use most often extracted from?
|
Salmon
|
|
|
How is Calcitonin administered?
|
Injection or Nasally
|
|
|
How do estrogens and SERMS like Raloxifene prevent/delay bone lsos in postmenopausal women?
|
May inhibit PTH-stimulated bine resorption
|
|
|
What effect do glucocorticoids have on bone maintenance?
|
They inhibit bone mineral maintenance, and chronic use can cause Osteoporosis.
They are used in intermediate-term tx of hypercalcemia |
|
|
What kind of drugs are the "-dronates"?
|
Bisphosphonates
|
|
|
What are examples of the Bisphosphonates?
|
Alendronate
Etidronate Ibandronate Pamidronate Risedronate Tiludronate Zoledronic acid |
|
|
How do bisphosphonates work?
|
- They reduce the both resorption and formation of bone by acting on the basic hydroxyapetite crystal
- Affect Vit.D production and Ca absorption from GI - Directly inhibit osteoCLASTS |
|
|
How do Bisphosphonates inhibit osteoclast survival?
|
by inhibiting Farnesyl Pyrophosphate Synthase
|
|
|
What states are Bisphosphonates used for?
|
HYPERcalcemia
& to treat Paget's Disease |
|
|
What is bisphosphonate commonly chronically used for?
|
Osteoporosis, to prevent and treat all forms of osteoporosis
|
|
|
Toxicities of LOW doses of Bisphosphonates:
|
Gastric & Esophageal Irritation
take w/ large quantities of water and avoid situations that permit esophageal reflux |
|
|
Toxicities of HIGHER doses of Bisphosphonates:
|
Renal Impairment & Osteonecrosis of the JAW
|
|
|
What is the main Calcimimmetic that we use?
|
Cinacalcet
|
|
|
How does Cinacalcet work?
|
Lowers PTH by activating the Ca-sensing receptor in the Parathyroid gland
|
|
|
What is Cinacalcet used for?
|
Tx of Secondary hyperparathyroidism in chronic kidney disease
Hypercalcemia in pts w/ parathyroid carcinoma |
|
|
Toxicities of Cinacalcet
|
Hypocalcemia
Adynamic Bone disease |
|
|
What is fluoride really useful in preventing?
|
Dental caries
|
|
|
What does acute toxicity of Fluoride usu. cause?
Whats a common cause of Acute Fluoride toxicity? |
Ingestion of Rat poison
|
|
|
How does Gallium Nitrate work?
|
by inhibiting bone resorption w/hypercalcemia assoc. w/malignancies & Paget's disease
|
|
|
What do you need to monitor in patients taking Gallium Nitrate?
|
Make sure pt is well hydrated and has good renal output
You want to prevent nephrotoxicity |
|
|
Which antibiotic is used to reduce serum Ca and bone resorption in Paget's disease and hypercalcemia?
|
Plicamycin
(mithramycin) |
|
|
Toxicities of Plicamycin
|
Thrombocytopenia
Hemorrhage Hepatic & Renal Damage |
|
|
What Diuretics affect serum and urinary Ca levels?
|
Thiazide diuretics
Furosemide |
|
|
What is Sevelamer?
|
A phosphate-binding gel thats used in combo with Ca supplements and dietary phosphate restriction to treat
hyperphosphatemia (from renal failure) hypopatathyroidism & Vitamin D intoxicatoin |
|
|
*Available Bisphosphonates
|
*Alendronate
Etidronate Pamidronate Risedronate Tiludronate Zoledronic acid |
|
|
* MOA of Bisphosphonates
|
* Inhibits osteoclast bone resorption
|
|
|
* Only Bisphosphonate available IV
|
* Etidronate
|
|
|
* Uses of bisphosphonates
|
* Osteoporosis
Paget's dz Osteolytic bone lesions Hypercalcemia from malignancy |
|
|
* Major SE of Bisphosphonates
|
* Chemical esophagitis
|
|
|
* Bisphosphonate that cannot be used on on continuous basis b/c i causes osteomalacia
|
* Etidronate
|
|
|
* Used for prevention of Postmenopausal osteoporosis in women
|
* Estrogen (HRT)
|
|
|
* Increase bone density, also being tested for breast CA prophylaxis
|
* Raloxifene (SERM - Selective Estrogen Replacement Modulator)
|
|
|
* Used INTRANASALLY and decreases bone resorption
|
* Calcitonin (Salmon prep)
|
|
|
* Used especially in postmenopausal women, dosage should be 1500 mg
|
* Calcium
|
|
|
* Vitamin given with Calcium to ensure proper absorption
|
* Vitamin D
|
