Parathyroid drugs Flashcards
Alendronate (Fosamax), Risedronate (Actonel)
Class: Bisphosphonate
Mech: Reduce osteoclastic bone resorption
Thera: Hypercalcemia; osteoporosis; Paget’s disease of bone; prevention of fractures in osteogenesis imperfecta
Other SE’s: Esophageal irritation
Misc: Oral formulation; patient must be sitting upright, fasting, for 30 minutes; takes several days to see effect
Ibandronate (Boniva)
Class: Bisphosphonate
Mech: Reduce osteoclastic bone resorption
Thera: Hypercalcemia; osteoporosis; Paget’s disease of bone; prevention of fractures in osteogenesis imperfecta
Other SE’s: Esophageal irritation
Misc: Oral and IV formulations; patient must be sitting upright, fasting, for 30 minutes; takes several days to see effect
Pamidronate (Aredia)
Class: Bisphosphonate
Mech: Reduce osteoclastic bone resorption
Thera: Hypercalcemia of malignancy; Paget’s disease of bone; prevention of fractures in osteogenesis imperfecta
Important SE’s: Serum creatinine elevation
Other SE’s: Fever, flu-like symptoms
Misc: Bypasses GI tract (given IV); takes several days to see effect for lowering calcium
Zoledronic acid (Reclast)
Class: Bisphosphonate
Mech: Reduce osteoclastic bone resorption
Thera: Hypercalcemia of malignancy; Paget’s disease of bone; prevention of fractures in osteogenesis imperfecta
Important SE’s: Serum creatinine elevation
Other SE’s: Fever, flu-like symptoms
Misc: Bypasses GI tract (given IV); takes several days to see effect for lowering calcium
Cinacalcet (Sensipar)
Class: Calcimimetic
Mech: Reduces PTH and serum calcium levels
Thera: Secondary hyperparathyroidism from renal disease; parathyroid carcinoma; hypercalcemia in primary hyperparathyroidism not treatable by surgery
Calcitonin (Miacalcin)
Class: Amino acid peptide
Mech: Increases urinary calcium excretion, inhibits bone reabsorption (modest effect)
Thera: Short-term relief of hypercalcemia; osteoporosis (reduce vertebral fractures); Paget’s disease of bone
Other SE’s: Minimal (e.g., rhinitis)
Misc; No longer recommended for use in nasal spray form because of increased cancer risk. Can still use SQ or IM. Tachyphylaxis in 2-3 days; often used to bridge treatment for other medication
Teriparatide (Forteo)
Class: PTH analog
Mech: Short bursts given SQ, stimulating bone resorption and bone formation via osteoblasts
Thera: Osteoporosis (high risk patients who have failed other treatments)
Other SE’s: Transient mild hypercalcemia
Misc: Contraindicated in those with increased chance of osteosarcoma (e.g., Paget’s disease of the bone, radiation exposure)
Raloxifene (Evista)
Class: Selective estrogen receptor modulator
Mech: Selectively activates certain estrogen receptors, but blocks others
Thera: Osteoporosis
Important SE’s: Increase risk of hot flashes, DVT
Corticosteroids
Mech: Decreases production of 1,25 vitamin D; may inhibit growth of neoplastic lymphoid tissue
Thera: Hypercalcemia from vitamin D intoxication, granulomatous diseases, hematologic malignancies
Denosumab (Prolia)
Class: Monoclonal antibody
Mech: RANK ligand inhibitor (targets early effect of osteoclasts on bone)
Thera: Osteoporosis
Misc: can give at any GFR but need to exclude other causes of renal osteodystrophy
Calcium carbonate, Calcium acetate, Sevelamer (Renvela)
Mech: Binds phosphate
Thera: Secondary hyperparathyroidism from renal disease
Cortical bone predominates in the _____; trabecular bone predominates in the _____
shafts of the long bones;
vertebral bodies, ribs, pelvis, ends of long bones
The inorganic matrix of bone is largely composed of _____, a mineral composed of
hydroxyapatite;
Ca and P
Biologic activity of PTH resides in _____; it is secreted by what? Its secretion is controlled by what?
first 34 residues; the four parathyroid glands;
serum IONIZED Ca, such that if Ca is low, PTH is stimulated, but if Ca is high, PTH suppressed
Discuss percentages regarding Ca in the body:
99% in skeleton, 1% in ECF; 3 forms: 1. ionized Ca (50%) 2. protein bound Ca (40%) 3. Complexed to bicarb, citrate, phos (10%)
What is physiologically the most important Ca? What accounts for most of its protein binding?
Free/ionized;
albumin!!
P levels influenced by ____ and _____; what promotes its reabsorption in the ____ and what promotes excretion?
vit D3 and PTH;
phosphate deletion, hypoparathyroidism, hypocalcemia increase reabsorption;
PTH, PTHrP, hypercalcemia, hypokalemia, hypomanesemia, calcitonin, glucocorticoids, and diuretics promote excretion
For Mg, what is it necessary for? Where is it excreted and what can interfere with its reabsorption at loop of Henle?
Release of PTH and action of hormone on its target tissues;
primarily renally excreted;
drugs like furosemide and cisplatin inhibit
Renal production of Vit D3 is tightly regulated by _____ through
Ca levels; PTH and phosphorus
In cases of hypercalcemia, most common causes and what should be ordered? What is PTH levels in either of these causes?
Think malignancy or hyperparathyroidism;
if primary, PTH high or normal;
if PTH is low, think about PTHrP, vit D levels, and 24 hr urine Ca
Some major causes of hypercalcemia?
- Primary hyperparathyroidism
- malignant disease (osteolytic metastases with breast cancer and MM)
- Sarcoid, TB, granulomatous diseases
- Milk-alkali syndrome (Tums)
- FHH
- Vit D or A intoxication
Usually, what leads to primary hyperparathyroidism? How can you diagnose it?
think benign, solitary adenoma usually, if not hyperplasia of all four glands;
see elevated Ca, elevated or normal PTH, low P maybe, and elevated urine Ca
Treatment of primary hyperparathyroidism? Who is recommended for treatment?
Remove abnormal parathyroid tissue, especially with overt bone disease, kidney stones, or life threatening hypercalcemia;
think 1.0 mg/dL higher than normal, T score < -2.5, vertebral fracture on X-ray, creatinine clearance < 60, 24 hr urine for Ca > 400 mg/day, if you have nephrolithiasis or nephrocalcinosis, and if LESS THAN 50
Treatment of primary hyperpara:
- adequate hydration and ambulation
- still need moderate Ca intake
- bisphosphonates for low bone density in those w/o surgery
- Calcimimetics: reduce PTH and serum Ca levels (alter function of Ca sensing receptor)
- Sensipar: for hyperpara in renal disease and parathyroid carcinoma, and also primary HPT who won’t have/refuse surgery
