01-31 Bone PHARM

Question 1

diuretics

Answer 1

thiazides are Ca++ sparing and can cause hypercalcemia

Question 2

bisphosphonates
—Example meds
—Indication
—MOA
—ADRs

Answer 2

—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!)

Question 3

calcitonin
—Example meds
—Indication
—MOA
—ADRs

Answer 3

—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

Question 4

calcium salts
—P.O. Forms
——names
——relativey
—IV Forms

Answer 4

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!

Question 5

VitD
—Forms available
—MOA on gut

Answer 5

—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

Question 6

HRT

Answer 6

Similar to SERMS

Question 7

SERMs
—Example meds
—Indication
—MOA

Answer 7

—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

Question 8

exogenous PTH
—discussion
—Rx name
—MOA

Answer 8

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

Question 9

denosumab

Answer 9

Denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL. This mimics the natural action of osteoprotegerin (OPG), an endogenous RANKL inhibitor

Question 10

Draw the relationship between serum [Ca] and:
—kidneys
—intestines
—bones
—parathyroids

Answer 10

[Image q10] See slide 4

Question 11

Hypercalcemia
—Frequency
—Causes

Answer 11

Frequency – relatively common
Causes - 90% of cases due to malignancy or hyperparathyroidism
—Hyperparathyroidism – mild and prolonged
—Malignancy – more severe,

Question 12

Goals of hypercalcemia tx?

—by organ involved

Answer 12

—Increase urinary calcium excretion
—Diminish intestinal absorption of calcium
—Inhibit accelerated bone resorption

Question 13

Tx of hypercalcemia generally

Answer 13

STAT
—1. ‪↓‬ dietary Ca & VitD
—2. stop thiazides (Ca-sparing)
—3. ↑ salt & H2O (diuresis lowers [Ca])

Then tx underlying Disease

Question 14

Hypocalcemia
—Frequency
—Causes

Answer 14

—Frequency - less frequent than hypercalcemia, seen in hospitalized patients
—Causes – chronic and acute renal failure, vitamin D deficiency, Mg+ deficiency, acute pancreatitis, hypoparathyroidism

Question 15

Tx of Hypocalcemia

Answer 15

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!

Question 16

Hyperparathyroidism
—Frequency
—Causes

Answer 16

Frequency
—common, 1 in 500-1000

Causes
—Primary – parathyroid adenoma or hyperplasia, carcinoma (rare) – treat with parathyroidectomy
—Secondary – chronic renal failure, malabsorption syndromes
—Tertiary – progression into autonomous hypersecretion of PTH associated with hypercalcemia

Question 17

Calcimimetics
—Example
—Indication
—MOA
—ADRs

Answer 17

**rarely used; helpful mech for edu purposes
—Example: cinacalcet HCl
—Indication: 2° hyperPTHism in CKD; hypercalcemia in parathyroid carcinoma; ?1° HTN
—MOA: tickles Ca_ receptor on parathyroids tricking them into thinking serum [Ca] is higher than it actually is; actually looks nothing like Ca2+!
—ADRs: hypocalcemia, n/v

Question 18

Parathyroid response to low Vit D

Answer 18

increases PTH

—this makes sense but is bad for bone if it continues for any extended period of time!!

Question 19

Tx for osteoporosis: general categories w/ examples of each

Answer 19

—supplement (give Ca & D)
—prevent resorption (bisphosphonates, SERMS, danosumab, calcintonin)
—encourage bone growth w/ anabolic agents (i.e. PTH)