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31 Cards in this Set
- Front
- Back
Hypercalcemia: Symptoms
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decreased muscle tone
-muscle weakness and flaccidity -hypoexcitability of nerves -coma -death |
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Hypocalcemia: Symptoms
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increased muscle tone
-tetany -hyperexcitability of nerves -convulsions -death |
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Diseases of calcium homeostasis
and bone: |
Osteoporosis***
Tumor invasion of bone** PTH-secreting tumors Paget’s disease of bone Kidney disease/renal failure: -secondary hyperparathyroidism** Vitamin D deficiency: -rickets, osteomalacia body is very good at maintaining serum Ca---usually see diseases caused by the bodies attempt to keep that homeostasis (eg osteoporosis) |
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Calcitonin
MOA effects on ca |
MOA---Gs--AC (on actual osteoclasts)
sc,iv,intranasal Decreases Blood Ca2+ Levels • Prevents bone resorption Inhibits osteoclasts • Inhibits Ca & phosphate reabsorption in kidney • Inhibits 1-alpha hydroxylase in kidney Enzyme that activates Vitamin D (good analgesic in bone pain too) |
|
Calcitonin
indications |
• Osteoporosis
Healing fractures Reducing pain of osteoporosis • Paget’s disease of bone • Hypercalcemia • Analgesic properties Good in bone pain Paget’s, osteoporosis, cancer, phantom limb Peripheral & central mechanisms |
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Salmon Calcitonin
uses |
• SubQ, IV, intranasal
• Prepared synthetically • More potent, longer duration of action Preferred form same indications but better than human calcitonin |
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possible drugs to use in hypercalcemia
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Calcitonin
(Human) Calcitonin (Salmon)better -Bisphosphonates (2nd Generation) Alendronate Risedronate Etidronate -LOOP DIURETICS***great for this Furosemide Bumetinide Ethacrynic Acid Torsemide -cinacalcet hydrochloride |
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Calcitonin
SEs CIs |
• Injectable
Nausea, allergic reactions, flushing • Intranasal Nasal dryness, irritation, rhinitis, Headache • Most patients lose effectiveness after ~2yrs (^PTH, osteoclast escape) • Contraindications Hypocalcemia Pregnancy Breast feeding Fish hypersensitivity not a problem in recombinant form |
|
cinacalcet hydrochloride
MoA |
Ca mimetic
• Increases the sensitivity of the calcium sensing receptors on the parathyroid cells to extracellular calcium The cells reduce secretion of parathyroid hormone at lower levels of Ca2+ Lower levels of PTH in blood means falling Ca2+ levels |
|
cinacalcet hydrochloride
indications |
• Treatment of Hypercalcemia
Secondary hyperparathyroidism Pts with chronic renal disease on dialysis Pts with parathyroid carcinoma |
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Bisphosphonates (2nd Generation)
MoA |
• Structurally related to pyrophosphate
Binds hydroxyapatite of bone and inhibits resorption of bone. • Inhibit bone resorption Decrease Serum Ca2+*** Osteoclast inhibitors • Less toxic effects on bone mineralization than 1st generation Greater (safer) margin (they increased fractures and bone pain) |
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Bisphosphonates (2nd Generation)
Named |
-ORAL
Alendronate Risedronate Ibandronate -IV pamidronate zoledronate |
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Bisphosphonates (2nd Generation
INDICATIONS |
~dronate family
• Paget’s disease of bone • Osteoporosis treatment and prophylaxis Alendronate is drug of choice for steroid-induced osteoporosis • Osteolytic metastases (hypercalemia) IV formulations more for Malignancies, and osteoporosis----associated with---osteonecrosis of the jaw |
|
Bisphosphonates (2nd Generation
SEs CIs |
IV-associated with---osteonecrosis of the jaw
oral-short T1/2 but stays in bone long time Take with full glass of H2O after overnight fast No other food/liquid for 30 min to 2 hrs. Patient must remain upright Prevent esophageal ulceration******* GI************* heartburn, esophageal irritation, abdominal pain, diarrhea • Contraindications GI disease NEW WARNING associated with severe muscle/bone PAIN***and very long acting drug |
|
LOOP diuretics and ca
plus indications |
decrease SERum CALcium
• Inhibits K+ recycling … prevents generation of lumen positive (+) voltage Can’t reabsorb Na+, Mg2+, Ca2+, or K+ by paracellular route (reduce driving force Treatment of Hypercalcemia Used in combination an infusion of isotonic saline |
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Indications for Vitamin D analogs:
|
-osteoporosis
-renal osteodystrophy -Vitamin D deficiency rickets osteomalacia -hypocalcemia -hypophosphatemia -hypoparathyroidism |
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Vitamin D analogs
MOA |
promote absorption
of calcium and phosphate in the gastrointestinal tract. usually taken with fatty food and a calcium supplement |
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Vitamin D analogs
NAMED |
Calcifediol -25
-Calcitriol -1,25 -Ergocalciferol -nothin -Dihydrotachysterol -1 |
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Calcifediol
|
• 25-Hydroxycholecalciferol
Activated in kidneys by hydroxylation at the 1 position Must have renal function Less effective in pts with renal failure |
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Calcitriol
|
• 1, 25-Hydroxycholecalciferol
Active hormone 2x the activity of calcifediol Rapid onset |
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-Ergocalciferol
|
naked
• Activated in liver at the 25 position • Activated in kidneys at 1 position • Must have liver and kidney function |
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Dihydrotachysterol
|
1, already
• Activated in liver at the 25 position • No conversion in kidneys required |
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Vit D usaully taken with...
but |
usually taken with food
not wheat bran, rhubarb, spinach and Calcium Ca citrate may be better tha Ca carbonate (not sure if these decrease Ca or Vit D I think Ca) |
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Ca Supplements
formulations SEs |
Calcium citrate may be better absorbed than calcium carbonate.
Calcium supplements are generally well-tolerated. GI effects such as constipation, bloating, and excess gas may be alleviated by switching preparations or by increasing fluid intake ACUTE HYPOCALCEMIA Ca salts IV |
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Ca Supplements
Drug interactions |
Calcium can interfere with absorption
of other minerals or drugs: Fl- (fluoride), iron, zinc beta-blockers salicylates bisphosphonates tetracycline |
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Osteoporosis:
defined |
Loss in bone mineralization and
decreased bone density. Especially common in postmenopausal women due to loss of estrogen with the menopause. The greatest bone loss occurs in the first five years after the menopause. |
|
Drug-induced osteopenia:
culprits |
--Glucocorticoids inhibit Ca
abs in the GUT and direct inhibitory effects on bone, causing osteoporosis. --anticonvulsants, phenytoin and phenobarbital inhibit Ca absorption from the intestines. --Leuprolide--drug induced E loss in bone(GnRH superAg) -SSRIs--bones have R but scetchy Rel. DISEASE induced---PrLinoma (-LH,FSH) |
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Osteoporosis
Tx PREVENT |
Bisphosphonates-prev further loss
•Raloxifene (SERM-E ag in bone) NO rebuild •Estrogen replacement therapy •Calcium/Vitamin D supplementation--prev further loss •Calcitonin--heal fractures and red pain •Teriparatide (parathyroid hormone) |
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Teriparatide
indication |
= PTH
only treatment for osteoporosis that can actually stimulate bone formation |
|
Teriparatide
MoA |
PTH
• Intermittent administration (once daily) of PTH stimulates new bone formation Stimulates osteoclasts to build new bone • Continuous PTH causes bone breakdown MoA Stimulation of Gs and Gq receptor/activation of AC and activation of phospholipase Cβ. |
|
Osteoporosis
RACE GENETICS |
Loss in bone mineralization and decreased bone density.
● 1:2 white women/Asian women ● 1:8 men and other women definately runs in families |