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31 Cards in this Set

  • Front
  • Back
Hypercalcemia: Symptoms
decreased muscle tone
-muscle weakness and flaccidity
-hypoexcitability of nerves
-coma
-death
Hypocalcemia: Symptoms
increased muscle tone
-tetany
-hyperexcitability of nerves
-convulsions
-death
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)
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
Salmon Calcitonin
uses
• SubQ, IV, intranasal
• Prepared synthetically
• More potent, longer duration of action
 Preferred form
same indications but better than human calcitonin
possible drugs to use in hypercalcemia
Calcitonin
(Human)
Calcitonin
(Salmon)better
-Bisphosphonates (2nd Generation)
Alendronate
Risedronate
Etidronate
-LOOP DIURETICS***great for this
Furosemide
Bumetinide
Ethacrynic Acid
Torsemide
-cinacalcet hydrochloride
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
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)
Bisphosphonates (2nd Generation)
Named
-ORAL
Alendronate
Risedronate
Ibandronate
-IV
pamidronate
zoledronate
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
Indications for Vitamin D analogs:
-osteoporosis
-renal osteodystrophy
-Vitamin D deficiency
rickets
osteomalacia
-hypocalcemia
-hypophosphatemia
-hypoparathyroidism
Vitamin D analogs
MOA
promote absorption
of calcium and phosphate in the
gastrointestinal tract.
usually taken with fatty food and a calcium supplement
Vitamin D analogs
NAMED
Calcifediol -25

-Calcitriol -1,25

-Ergocalciferol -nothin

-Dihydrotachysterol -1
Calcifediol
• 25-Hydroxycholecalciferol
 Activated in kidneys by hydroxylation at the 1 position
 Must have renal function
 Less effective in pts with renal failure
Calcitriol
• 1, 25-Hydroxycholecalciferol
  Active hormone
 2x the activity of calcifediol
 Rapid onset
-Ergocalciferol
naked
• Activated in liver at the 25 position
• Activated in kidneys at 1 position
• Must have liver and kidney function
Dihydrotachysterol
1, already
• Activated in liver at the 25 position
• No conversion in kidneys required
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)
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
Ca Supplements
Drug interactions
Calcium can interfere with absorption
of other minerals or drugs:

Fl- (fluoride), iron, zinc
beta-blockers
salicylates
bisphosphonates
tetracycline
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)
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)
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