Calcium and Bone Drugs Flashcards
Calcium supplements
Calcium carbonate
Calcium citrate
Calcium supplements - MoA
Important for: Bone remodeling, nerve, muscle function, gland secretion, blood coagulation, enzyme activities
Calcium supplements - Clinical use
Hypocalcemia, osteoporosis
Calcium supplements - Adverse effects
Modestly increased risk of MI
Calcium supplements - Interactions
Decreased absorption of ciprofloxacin, fluoride, phenytoin, levothyroxine, tetracycline
Vitamin D supplements
Cholecalciferol (Vitamin D3)
Ergocalciferol (Vitamin D2)
Cholecalciferol - MoA
Increased synthesis of calcium-binding protein
increases calcium absorption.
Stimulation of bone resorption
Ergocalciferol - MoA
Activated in liver and kidneys to form calcitriol. Increases Ca and phosphorous absorption from the gut
Vitamin D supplements - Clinical use
Prevention and treatment of rickets (vit D-dependant and -resistant).
Prevention of osteoporosis.
Hypocalcemia (by hypoparathyroidism)
Tetani (post-op and idiopathic).
Prevention of vit D deficiency in chronic renal failure
Vitamin D supplements - Adverse effects
Hypercalcemia
Hypercalciuria
Vitamin D supplements - Interactions
Cholestyramine inhibits absorption.
Phenytoin and barbiturates: increased vit D metabolism and deficiency.
Bisphosphonates - Classification
Bone resorption inhibitors
Bisphosphonates - MoA
Absorb hydroxyapatite and become permanent parts of the bone structure (terminal half life is 10 years). Inhibits osteoclast activity by preventing them to attach to bone
Bisphosphonates - Clinical use
Osteoporosis, Paget disease of the bone, hypercalcemia, osteolytic bone lesions in metastatic cancer
Bisphosphonates - Contraindications
Dull, aching pain in the thigh or groin
Bisphosphonates - Adverse effects
Espohageal erosion, GI distress.
Long-term use: atypical (subtrochanteric & diaphysial) femur fractures. Poor oral health: Osteonecrosis of the jaw
Bisphosphonates reduces the risk of?
Breast cancer
Bisphosphonates - Interactions
Calcium supplements & antacids: decreases absorption of bisphosphonate
1st generation bisphosphonate
Etidronate
2nd generation bisphosphonates
Alendronate
Pamidronate
Risedronate
Tiludronate
2nd generation bisphosphonates - Clinical use
ALL: Paget disease of the bone (symptomatic/candidates for surgery)
Alendronate - Clinical use
Osteoporosis (all forms)
Alendronate - Adverse effects
GI distress only with high doses, mild and transient nausea, dyspepsia, constipation, diarrhea
Pamidronate - Clinical use
Hypercalcemia associated with cancer.
Risedronate - Clinical use
Prevention and treatment of osteoporosis in postmenopausal women.
Tiludronate - MoA
Decreases tyrosine phosphase activity in osteoclasts, causing osteoclast detachment from bone. Inhibits osteoclastic proton pumps
3rd generation bisphosphonates
Ibandronate
Zoledronic acid
Ibandronate - Clinical use
Prevention and treatment of osteoporosis in postmenopausal women
Zoledronic acid - Clinical use
Hypercalcemia associated with cancer
Estrogen + related drugs
Estrogen
Raloxifene
Estrogen - MoA
Inhibits production of bone cell cytokines (IL-1, TNF, IL-6, ect.), causing reduced bone resorption by decreasing formation and activation of osteoclasts.
Estrogen - Clinical use
Relief of menopausal symptoms
Estrogen - Contraindications
high doses in treatment for osteoporosis (increased risk of breast cancer and cardiovascular events)
Raloxifene - MoA
Activates estrogen receptors in bone while having antiestrogen effects in breast and uterine tissues
Raloxifene - Clinical use
Postmenopausal osteoporosis
Raloxifene - Adverse effects
Intensify hot flashes, increased risk of stroke, pulmonary emboli, DVT
Calcitonin - MoA
Binds to osteoclastic receptors, increases cAMP levels.
Short-term effect: inhibits osteoclast activity, decreases bone resorption, decreases serum Ca concentrations
Calcitonin - Clinical use
Osteoporosis: women who cannot tolerate other treatments: parenterally/nasal adm.
Paget disease of bone, hypercalcemia (adm subcut/IM)
Denosumab - Classification
Human immunoglobulin G2 monoclonal antibody, RANKL antibody
Denosumab - MoA
Inactivation of osteoclastic gene transcription by inhibition of RANKL (transmembrane protein).
Denosumab - Clinical use
Osteoporosis, prevention of skeletal-related events in breast, prostate cancer + other tumors
Denosumab - Adverse effects
Back, extremity, musculoskeletal pain, hypercholesterolemia, cystitis, skin reactions, hypocalcemia, slight increase in malignancies (not established)
Teriparatide - Classification
Recombinant form of human PTH
Teriparatide - MoA
Increase bone formation (short-term).
Long-term: stimulate bone resorption
Teriparatide - Clinical use
Osteoporosis (postmenopausal women and hypogonadal men at high risk bone fracture)
Teriparatide - Contraindications
Rapid cessation of the drug, treatment should be followed by bisphosphatonates
Not given to people at increased risk for osteosarcoma (Paget disease of the bone)
Teriparatide - Adverse effects
Increased incidence of osteosarcoma
Strontium ranelate - MoA
Decreases osteoclastic activity & bone resorption in newly formed bone. Induces proliferation of osteoblasts
Strontium ranelate - Clinical use
Prevention of osteoporosis
Prevent vertebral and non vertebral fractures
Strontium ranelate - Adverse effects
Minor GI distress
Increased risk or venous and pulmonary thromboembolism and MI
Sodium fluoride - MoA
Stored in bone and teeth. Replaces the hydroxyl group in calcium phosphate salts and form fluorapatite (more resistant to erosion)
Sodium fluoride - Clinical use
Prevention of tooth decay and caries. Potential application for osteoporosis
Sodium fluoride - Adverse effects
Excessive hardening of the bone (osteosclerosis), formation of demineralized bone, GI distress, interfere with Ca and Mg absorption
Cinacalet - MoA
Increase the sensitivity of calcium-sensing receptors in the parathyroid gland to extracellular calcium, leading to decreased secretion of PTH and lowering of serum calcium levels
Cinacalet - Clinical use
Hyperparathyroidism in adult patients with chronic kidney disease who are on dialysis
Hypercalcemia in patients with parathyroid cancer.