01-31 Bone PHARM Flashcards
diuretics
thiazides are Ca++ sparing and can cause hypercalcemia
bisphosphonates —Example meds —Indication —MOA —ADRs
—examples: pamidronate (lasts wks), zolendronate (newer, lasts months), alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva)
——These all just have diff R groups and therefore diff T1/2’s
—indication: hypercalcemia and osteoporosis
—MOA: prevents bone resorption; is a pyrophosphate (two inorganic PO4’s) look-alike; binds to bone matrix; gets taken up by osteoclasts; inhibits their fxn and causes apoptosis
—ADRs:
——acute: flu-like sx common
——nephrotoxicity from Ca++ precip
——GI toxicity: stay standing for 30 mins s/p taking
——very rare: jaw necrosis (so screen for dental work and have that done first!)
calcitonin —Example meds —Indication —MOA —ADRs
—example: synthetic salmon calcitonin
—Indication: hypercalcemia, ?osteoporosis, bone pain
—MOA: antiresorptive/analgesic; binds GPCR on osteoCLasts → ↓ bone resorption; some ↑ renal Ca wasting
—ADRs: resistance (∆s in receptors and Ab formation)
**second line because effect is short-term given propensity for resistance
calcium salts —P.O. Forms ——names ——relativey —IV Forms
1) calcium carbonate
P.O. FORMS
—ADRs for both: GI (e.g. constip), ↓ absorption of other minerals, drugs; milk-alkali syndrome
——highest Ca++ content (40%)
——absorption impaired w/ achlorhydria (e.g. PPI Rx)
——half as much Ca++ content (21%)
——but more bioavailable
IV FORMS
—calcium gluconate is best
—CaCl2 give more Ca but burns veins more
——watch out for extravasation!
VitD
—Forms available
—MOA on gut
—Forms: PO ergocalciferol (D2 = no OH yet), PO cholecalciferol (D3 = 25OH-D), PO/IV calcitriol (1,25(OH)2-D; rapid but shorter T1/2)
—MOA on gut: binds and forms complex w/ receptor that relocates into the nucleus of the enterocyte and ↑ calbindin synth
—ADRs: fat malabsorption; hypervitaminosis D → hypercalcemia, kidney dysfxn, stones
HRT
Similar to SERMS
SERMs
—Example meds
—Indication
—MOA
—Example: PO raloxifene
—Indication: postmenopausal osteoporosis (does not help w/ menopausal sx); less effective than other osteoporosis Rx
—MOA: estrogenic effects on bone but antagonist at breast and uterus
exogenous PTH
—discussion
—Rx name
—MOA
all other osteoporosis meds mentioned thus far assume that bone FORMATION is still happening, just that is is being outpaced by bone resorption
—if this is not the case, then add PTH
—teriparatide
—tricky because it normal plays the role of reducing bone mass in order to maintain serum [Ca]; make intermittent elevation (t take
denosumab
Denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL. This mimics the natural action of osteoprotegerin (OPG), an endogenous RANKL inhibitor
Draw the relationship between serum [Ca] and: —kidneys —intestines —bones —parathyroids
[Image q10] See slide 4
Hypercalcemia
—Frequency
—Causes
Frequency – relatively common
Causes - 90% of cases due to malignancy or hyperparathyroidism
—Hyperparathyroidism – mild and prolonged
—Malignancy – more severe,
Goals of hypercalcemia tx?
—by organ involved
—Increase urinary calcium excretion
—Diminish intestinal absorption of calcium
—Inhibit accelerated bone resorption
Tx of hypercalcemia generally
STAT
—1. ↓ dietary Ca & VitD
—2. stop thiazides (Ca-sparing)
—3. ↑ salt & H2O (diuresis lowers [Ca])
Then tx underlying Disease
Hypocalcemia
—Frequency
—Causes
—Frequency - less frequent than hypercalcemia, seen in hospitalized patients
—Causes – chronic and acute renal failure, vitamin D deficiency, Mg+ deficiency, acute pancreatitis, hypoparathyroidism
Tx of Hypocalcemia
Measure ionized Ca++ and check albumin to stratify tx:
—mild and asx: oral Ca supplements w/ VitD (consider calcitrol which is 1,25OH-D)
—acute/sx: IV supplementation: calcium gluconate is best, CaCl2 give more Ca but burns veins more
——watch out for extravasation!
