Calcium-Regulating Hormones and Related Drugs

Question 1

Calcium Salts

Answer 1

Calcium Gluconate
Calcium Gluceptate
Calcium Carbonate
Calcium Citrate
Calcitonin

Question 2

Vitamin D Drugs

Answer 2

Cholecalciferol
Ergocalciferol
Dihydrotachysterol
Calcifediol
Calcitriol

Question 3

Bisphosphonates

Answer 3

Alendronate
Zoledronate
Ibandronate

Question 4

Vitamin D

Answer 4

Steroid-like hormone (7-dehydrocholesterol)
Requires UV light
D3 = cholecalciferol
D2 = ergocalciferol (plant)
1-OH’n : Kidney (sim by PTH and low Pi, inhib by 1,25-(OH)2-D)
25-OH’n: Liver
1,25-(OH)2-D: calcitriol, active form, inhibits 1-OH’n and PTH
Bone: enhances resorption of Ca++ and Pi
GI: increases Ca++ and Pi absorption (major site)
Kidney: increase reabsorption of Ca++ and Pi

Question 5

Calcitonin

Answer 5

From thyroid (dt hypercalcemia)
Stimulates Ca++ and Pi excretion (kidneys)
Decreases Ca++ release (bone)
Calcitonin R = GPCR, increase cAMP

Question 6

Endogenous PTH

Answer 6

Response to hypocalcemia
Rapid degradation (t1/2 = 2-5m)
PTHrp: hypercalcemia of malignancy

Question 7

Calcium salts

Answer 7

Dietary supplement 
Treat Ca++ deficiency 
Tx acute hypocalcemic tetany 
Need adequate D 
GI s/e: constipation, bloating, gas
Interactions: Fl, Fe, Zn, B-blockers, salicylates, phenytoin, bisphosphonates, tetracyclines, ciprofloxacin

Question 8

Calcium carbonate

Answer 8

Most concentrated (40% Ca++)
Not absorbed well without HCl (take with food)
Milk-alkali syndrome (hypercalcemia, decreased PTH, hyperphosphatemia, kidney stones, renal failure)

Question 9

Calcium citrate

Answer 9

Oral Tablets (9% Ca++)
More readily soluble
Does not require HCl
Patients with ACHLORHYDRIA

Question 10

Calcium gluconate

Answer 10

Oral, IV
Do not give IM (pain, irritation)
IV tx for ACUTE HYPOCALCCEMIC TETANY
Infuse slowly (avoid arrhythmia), least irritating

Question 11

Calcium gluceptate

Answer 11

Inject (IV, IM)

NOT IRRITATING on IM injection

Question 12

Vitamin D drugs

Answer 12

steroid hormone analogs
Lipid-soluble
Intracellular nuclear transcription factor receptors
Absorbed from intestine (req bile)
Long t1/2 (3-5 d)
Decreased effectiveness by phenytoin/phenobarbital
S/e: hypercalcemia, hypercalciuria

Question 13

Cholecalciferol

Answer 13

Oral
Pure D3
OTC

Question 14

Ergocalciferol

Answer 14

D2
Found in milk, other foods
Can be prescribed (–> reimbursed)
Tablets, capsules, oral sol’n, IM INJECTION

Question 15

Dihydrotachysterol

Answer 15

1-OH vitamin D analog
Does not require 1-(OH)’n
RENAL FAILURE, still needs liver 25-(OH)’n
Oral (tabs, capsules, sol’n)

Question 16

Calcifediol

Answer 16

25-OH-D3
LIVER DISEASE, still needs kidney 1-(OH)’n
Oral caps

Question 17

Calitriol

Answer 17

1,25-(OH)2-D3
No activation required
Oral or injection
effects to strong to handle

Question 18

Calcitonin

Answer 18

Peptide hormone/drug
Activates GPCR
Promote Ca++ & Pi excretion 
Decrease bone turnover (inhibits osteoclasts) 
PAGETS DISEASE

Question 19

Salmon Calcitonin

Answer 19

More potent, longer duration 
Peptide drug (IM, subQ, nasal spray) 
Short t1/2

Question 20

Bisphosphonates

Answer 20

Analog of pyrophosphate
Binds bond matrix
INHIBIT OSTEOCLASTS (chew)
some inhibit osteoblasts (build)
Alter cytokine signalling, apoptosis, and stem cell mobilization
Better than calcitonin (oral, cheaper, longer lasting)
PK: Take on empty stomach, avoid in renal dz (kidney excretion w/o metabolism)
S/e: Esophageal ulcers, osteonecrosis of the jaw (ONJ), increased (“atypical”) femoral fractures
Injection: reduction in breast and CRC?

Question 21

Alendronate

Answer 21

Osteoprosis, Paget’s dz
Oral, combo prep (+vit D)
New effervescent prep

Question 22

Ibandronate

Answer 22

Postmenopausal osteoporosis

Oral tabs, IV injection

Question 23

Zoledronate

Answer 23

Postmenopausal osteoporosis (IV)
PREVENTION + treatment
PAGET’S, hypercalcemia of malignancy (IV)
1x /year or 1x /2 years (very long duration)
Risk: renal impairment

Question 24

Teriparatide

Answer 24

Synthetic human PTH (shortened PTH analog)
GPCR –> cAMP
Bone: resorb Ca++ + Pi, major site of action
Kidney: reabsorb Ca++, decrease reabsorb Pi, stim 1-(OH)’n
GI: absorb Ca++ + Pi (indirect effects on vit D)
PK: daily injection subQ (STIMULATES BONE because not chronic), short action favors bone formation
Use: osteoporosis, GLUCOCORTICOID INDUCED osteoporosis
Increases bone formation, “ANABOLIC”
S/e: Nausea, cramps, HA, bone CA? (Paget’s, increased Alk Phos, prior radiation, open epiphyses)

Question 25

Denosumab

Answer 25

Monoclonal antibody against RANK-L
RANK-L: cytokine, activates osteoclasts, promotes bone resorption, estrogens suppress RANK-L
PK: peptide (injection), given 2x/year
Use: postmenopausal women with osteoporosis, for Ca++ issues in CA therapy (bone mets, osteoporosis dt androgen deprivation (prostate ca), aromatase inhibitors (breast ca))
S/e: ONJ, fracture risk, delayed fracture healing, back/muscle/bone pain, elevated chol/constipation, risk of infection, hypocalcemia

Question 26

Glucocorticoids

Answer 26

Decrease hypercalcemia (inhibit gut Ca++ absorption (antagonize vit D), toxic to immune cells)
Use: vit D toxicity, sarcoidosis, granulomas, lymphomas
Danger of osteoporosis (LT use)
Effects countered by bisphosphonates, denosumab, teriparatide