Parathyroid & Bone Pharmacology Flashcards
What are the guidelines (recommendations) for surgery in asymptomatic primary hyperparathyroidism based on serum calcium, skeletal and renal renal variables, and age? What are the guidelines for monitoring patients with asymptomatic primary hyperparathyroidism who do not undergo surgery?
Serum calcium 1.0 mg/dL > upper limit of normal. Skeletal: Bone mineral densitometry (BMD) by DXA: T-score , -2.5 @ lumbar, spine, total hip, femoral neck, or distal 1/3 radius or vertebral fracture by x-ray, CT, MRI, VFA (vertebral fracture assessment). Renal: Creatinine clearance 400 mg/d (>10 mmol/d) & increased stone risk by biochemical analysis, presence of nephrolithiasis or nephrocalcinosis by x-ray, US, or CT. Age:
What are the bisphosphonates? Which is most potent? MOA? These can be used for? Side effects? How must these be taken? Which can be given IV? How quickly do these drugs work?
Alandronate, Risedronate, Ibandronate, Pamdronate, Zoledronic Acid (most potent). (“Alan Rises with Pam to make a Band called Zoledronic Acid”) MOA: Reduce osteoclastic bone resorption, Used for: Hypercalcemia of any cause, osteoporosis, Paget’s disease of bone, prevention of fractures in osteogenesis imperfecta. Major side effect: Esophageal irritation. Pamdronate & Zoledronic Acid also cause creatinine elevation, transient fevere & flu-like symptoms These are oral formulation that must be taken with the patient sitting upright having fasted for 30 minutes. Pamdronate & Zoledronic Acid can be given IV. These take several days to see effect.
What calcimimetic is used? MOA? Used for?
Calcimimetic: Cinacalcet. MOA: Reduces PTH and serum calcium levels. Use: Primary hyperparathyroidism (with hypercalcemia) not treatable by surgery, Secondary hyperparathyroidism from renal disease, parathyroid carcinoma.
What is calcitonin? What does it do? When can we use this? What are side effects? This is no longer recommended as? Still, how can it be given? What happens after use, and what is the implication?
Calcitonin is an amino acid peptide. It increases urinary calcium excretion, inhibits bone reabsorption (modest effect). This is used for short-term relief of hypercalcemia (can lower calcium levels within 2-4 hours), osteoporosis (reduce vertebral fractures – but not used much in this manner), Paget’s disease of bone. Side effects are minimal (e.g., rhinitis). 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 due to downregulation of calcitonin receptors on osteoclasts, and thus this is often used to bridge treatment for other medications that may take longer to onset (e.g., bisphosphonates).
What PTH analog is used? How is this used and for what is it used? Side effects? Who is this contraindicated in?
PTH analog: Teriparatide Uniquely anabolic! Used via short bursts given SQ, stimulating bone resorption and bone formation via osteoblasts. Used for osteoporosis (high risk patients who have failed other treatments). Side effects: Transient mild hypercalcemia. Contraindicated in those with increased chance of osteosarcoma (e.g., Paget’s disease of the bone, radiation exposure).
Which SERM might we use for osteoporosis? Side effects?
Raloxifene. Side effects: Increased risk of hot flashes, DVT.
What effect of corticosteroids can be taken advantage of in those with hypercalcemia? Hypercalcemia from what causes can be treated with corticosteroids?
Decreases production of 1,25 vitamin D & may inhibit growth of neoplastic lymphoid tissue. Hypercalcemia from vitamin D intoxication, granulomatous diseases, hematologic malignancies.
What monoclonal antibody can be used to treat osteoporosis? MOA? Side effects? Contraindications?
Denosumab. RANK ligand inhibitor (targets early effect of osteoclasts on bone – it is antiresorptive). Side effects: Infection. Contraindication: Hypocalcemia.
What phosphate binders are used? These are used when?
Phosphate binders: Calcium carbonate, Calcium acetate, Sevelamer. These are used in secondary hyperparathyroidism due to chronic renal failure.
What medications are notable for inducing hypercalcemia? How can one differentiate between primary hyperparathyroidism and familial hypocalciuric hypercalcemia? Why is this important?
Lithium, Thiazide diuretics. To differentiate, a urinary calcium collection is needed. If the ratio of calcium clearance to creatinine clearance is less than 0.01, this suggests FHH. This is important because parathyroidectomy is not useful in patients with FHH.
What are the goals in the treatment of hypercalcemia? What are the treatment regimens?
Goals – 1. Decrease serum calcium concentration by expanding intravascular volume & increasing urinary calcium excretion. 2. Inhibit bone resorption (in the long run, we must save bone!!). Treatment – 1. Fluids: This helps prevent hypercalcemia-induced dehydration & causes a modest calcium excretion. Add loop diuretic once volume status has been restored to increase calciuria. 2. Bisphosphonates: The “cornerstone” of treatment. 3. Calcitonin. 4. Corticosteroids (if hypercalcemia is due to VD intoxication, granulomatous disease, hematologic malignancy). 5. Other: dialysis, ambulation, calcimimetics.
How do we treat primary hyperparathyroidism?
Ideally, surgery to remove the hyperparathyroidic glands. Hydration & ambulation + moderate calcium intake. Bisphosphonates to treat low bone density. Calcimimetics.
How do we treat hypocalcemia in the context of chronic renal failure?
Calcitriol +/- VD analogs (paracalcitol, doxercalciferol) IV or orally several times/week. Phosphate binders. Calcimimetics.
How do we treat hypoparathyroidism? What do we want to avoid?
Restore calcium and phosphorous with supplements, taking care to avoid hypercalciuria.
With a VD deficiency, which supplement is superior – cholecalciferol (D3) or ergocalciferol (D2)?
Cholecalciferol (D3) is superior to ergocalciferol (D2).
