Bine Mineral Homeostasis Flashcards
drugs that cause Nephrotoxicity
Pilamycin (Mithracin) - also thrombocytopenia and hepatotoxicity
Gallium nitrate
Drugs causing osteoporosis
–Corticosteroids –Heparin –Lithium –Anastrozole –Alcohol
Drugs causing osteomalacia
–Phenytoin
–Etidronate (More than 12 months use)
Etidronate AE
osteomalacia
Osteonecrosis of jaw and fractures
Bisphosphonates AE
Erosive esophagitis
Drugs preventing calcium excretion
USE?
Treat?
- Thiazide diuretics decreases the excretion of calcium by increasing reabsorption.
- Useful in prevention of renal stone formation
- Treatment of hypertension in osteoporosis patient.
Treatment of hypercalcemia
- Most cases are asymptomatic or may be mild.
- Severe cases present with stones (nephrolithiasis); bones (bone pain, myalgias, arthralgias or fractures); abdominal groans (abdominal pain, nausea, vomiting), thrones (sits on throne for polyuria) and psychiatric overtones (fatigue, depression, anxiety, sleep disturbances)
- Treatment:
- Furosemide and saline infusion
- Bisphosphonates
- Calcitonin
- Parathyroidectomy, if patient is symptomatic.
Parathyroid Hormone (PTH) MOA?
- PTH increase both osteoclasts and osteoblasts activity in bone via ligand RANKL, a TNF cytokine.
- PTH couple Gs receptors to increase cAMP in bone and renal tubular cells.
- High levels of PTH present continuously causes sub-periosteal bone resorption
- Low dose given intermittently increases new bone formation.
Teriparatide?
USE
AE
Recombinant PTH analog
•Pulsatile doses stimulate bone formation – in the form of intermittent S.C. injection.
•Whereas high doses causes resorption
•Useful in treatment of osteoporosis, provides significant intervention for restoring normal bone loss.
•AE: may cause transient hypercalcemia & hypercalciuria
- Used for less than 2-years –due to `increased risk of osteosarcoma.
Denosumab?
AE
is a RANK Ligand (RANKL) inhibitor •It is a monoclonal antibody. It binds with RANKL and prevents it from stimulating osteoclast differentiation and function. •Inhibit bone resorption •Used in osteoporosis •AE: increased risk of infections
Vitamin D MOA?
Vit. dependedt rickets?
•Acts by activating steroidal nuclear receptor
•Deficiency causes rickets in children and osteomalacia in adults.
Vitamin –D dependent Rickets:
1.Type I –defective 1α hydroxylase enzyme – ↓calcitriol –> ↓Ca and ↓PO4
2.Type II –defective receptor for Vitamin
Vitamin D derivatives names and use?
•Calcitriol is approved for the treatment of secondary hyperparathyroidism in patients with chronic renal disease and liver disease.
•Calcipotriol is approved for the treatment of psoriasis (topical application).
•Vitamin D supplements are used in osteoporosis, chronic renal failure, nutritional rickets due to inadequate dietary intake, chronic liver disease
- Cholecalciferol & Ergocalciferol are commonly added to Ca supplements and dairy products.
Vitamin D Chemical names - Generic names?
Vitamin D3 = Cholecalciferol Vitamin D2 = Ergocalciferol 1,25-Dihydroxyvitamin D3 = Calcitriol 1α-Hydroxyvitamin D2 = Doxercalciferol 19-nor-1,25-Dihydroxyvitamin D2 = Paricalcitol Calcipotriene = Calcipotriol
Sevelamer: USE
a phosphate binding drug used to prevent hyperphosphatemia in patients with chronic renal failure. Binds to dietary phosphate and prevents its absorption in GI.
Calcium preps
- Oral: Ca carbonate, Ca citrate, and Ca lactate
- I.V. Clacium gluconate for the treatement of hypocalcemic tetany
- It is used to counteract overdose of Magnesium sulfate used in eclampsia.
- AE: I.M. inj may cause necrosis and abscess formation. I.V. can result in thrombophlebitis.
Calcitonin
USE?
alternative form?
PK?
- A peptide hormone
- Approved for the treatment of osteoporosis and has been shown to increase bone mass and reduce spine fractures.
- Salmon calcitonin has a longer half life and greater potency.
- Available as injection and nasal spray.
Estrogens USE
AE
- Estrogens are effective in preventing the bone loss.
- Useful in preventive treatment of osteoporosis in post menopausal women
- Given as hormonal replacement therapy
Adverse effects:
–Thromboembolism
–Migraine
–Increased risk of breast and endometrial cancer.
SERMs (selective estrogen receptor modulators)-
TAMOXIFEN
USE?
AE?
•Tamoxifen: Estrogen antagonistic action in breast, while agonistic effect in bone and uterus.
•Primarily used in treatment of breast cancer, has beneficial effect on bone.
ADR: Increased risk of endometrial Ca and thromboembolism and hot flushes.
SERMs
- RALOXIFENE
USE
AE
- Raloxifene: Estrogen antagonistic action on breast and agonist at bone. Has no estrogenic effect on endometrium.
- It is approved for treatment of osteoporosis in post-menopausal women.
- ADR: thromboembolism, hot flushes, etc.
Bisphosphonates
MOA
PK
•MOA: They inhibit osteoclastic activity via ↓ farnesyl pyrophosphate synthesis by disrupting mevalonate pathway ↓ osteoclast H+ ATPase.
•1) They bind with hydroxyapatite in the bone and 2) Reduce resorption
Oral bioavailabality less than 10%
a) Etidronate –not for long-term use.
b) Alendronate c) Pamidronate (i.v), d) Risedronate,
Chronic use of Etidronate and Pamidronate can lead to?
may result in bone malformation ↓osteoblastic activity.
Bisphosphonates AE
AE:
1.Erosive esophagitis due to direct irritation to esophageal lining.
Prevented by
upright position after taking medication
Increase fluid intake
2. Etidronate associated with osteomalacia. Osteonecrosis of jaw & fractures
Cinacalcet
USE?
AE?
It activates calcium-sensing receptors in parathyroid cells, leading to decrease in PTH synthesis and release.
•Used in secondary hyperparathyroidism in chronic renal disease and hyperparathyroidism in patients with parathyroid carcinoma.
•Adverse effects: Nausea, hypocalcemia
Fluoride exposure?
–Chronic exposure can lead to new bone synthesis which is denser but brittle.
•Plicamycin (Mithracin):
USE
AE
–Cytotoxic anticancer drug
–Useful in cancer-related hypercalcemia
–ADR: Thrombocytopenia, Hepatic and renal toxicity
•Gallium nitrate
USE
AE
–Inhibits bone resorption, useful in cancer-related hypercalcemia
–Nephrotoxic
