Calcium-Regulating Hormones and Related Drugs Flashcards
Calcium Salts
Calcium Gluconate Calcium Gluceptate Calcium Carbonate Calcium Citrate Calcitonin
Vitamin D Drugs
Cholecalciferol Ergocalciferol Dihydrotachysterol Calcifediol Calcitriol
Bisphosphonates
Alendronate
Zoledronate
Ibandronate
Vitamin D
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
Calcitonin
From thyroid (dt hypercalcemia)
Stimulates Ca++ and Pi excretion (kidneys)
Decreases Ca++ release (bone)
Calcitonin R = GPCR, increase cAMP
Endogenous PTH
Response to hypocalcemia
Rapid degradation (t1/2 = 2-5m)
PTHrp: hypercalcemia of malignancy
Calcium salts
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
Calcium carbonate
Most concentrated (40% Ca++)
Not absorbed well without HCl (take with food)
Milk-alkali syndrome (hypercalcemia, decreased PTH, hyperphosphatemia, kidney stones, renal failure)
Calcium citrate
Oral Tablets (9% Ca++)
More readily soluble
Does not require HCl
Patients with ACHLORHYDRIA
Calcium gluconate
Oral, IV
Do not give IM (pain, irritation)
IV tx for ACUTE HYPOCALCCEMIC TETANY
Infuse slowly (avoid arrhythmia), least irritating
Calcium gluceptate
Inject (IV, IM)
NOT IRRITATING on IM injection
Vitamin D drugs
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
Cholecalciferol
Oral
Pure D3
OTC
Ergocalciferol
D2
Found in milk, other foods
Can be prescribed (–> reimbursed)
Tablets, capsules, oral sol’n, IM INJECTION
Dihydrotachysterol
1-OH vitamin D analog
Does not require 1-(OH)’n
RENAL FAILURE, still needs liver 25-(OH)’n
Oral (tabs, capsules, sol’n)
Calcifediol
25-OH-D3
LIVER DISEASE, still needs kidney 1-(OH)’n
Oral caps
Calitriol
1,25-(OH)2-D3
No activation required
Oral or injection
effects to strong to handle
Calcitonin
Peptide hormone/drug Activates GPCR Promote Ca++ & Pi excretion Decrease bone turnover (inhibits osteoclasts) PAGETS DISEASE
Salmon Calcitonin
More potent, longer duration Peptide drug (IM, subQ, nasal spray) Short t1/2
Bisphosphonates
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?
Alendronate
Osteoprosis, Paget’s dz
Oral, combo prep (+vit D)
New effervescent prep
Ibandronate
Postmenopausal osteoporosis
Oral tabs, IV injection
Zoledronate
Postmenopausal osteoporosis (IV)
PREVENTION + treatment
PAGET’S, hypercalcemia of malignancy (IV)
1x /year or 1x /2 years (very long duration)
Risk: renal impairment
Teriparatide
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)
Denosumab
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
Glucocorticoids
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
