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44 Cards in this Set
- Front
- Back
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Reading: Basic and Clinical Pharmacology, Chapter 42, pp 706 – 723, 2007;
recommend NEJM 357: 266-281, 2007 |
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___% of post menopausal women don't have recommended amounts of vitamin D
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50
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HOw do you get previtamin D3?
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7-dehydrocholesterol + UVB
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How do you get vitamin D3?
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previtamin D3 + heat
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How do you get vitamin D2?
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diet
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PTH administered how has been shown to increase bone formation and this is a potential new therapy for osteoporosis
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PTH administered intermittently
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Chronic PTH elevation increases bone remodeling and increased _______-mediated bone resorption
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osteoclast
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Neuro effects of hypocalcemia
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Excitation thresholds
CNS dysfunction ranging from confusion to seizures Paresthesia (tingling sensation) in extremities Muscle spasm, tetany: laryngospasm- life threatening muscle cramps |
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Neuro effects of hypercalcemia
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Excitation thresholds
CNS depression: lethargy depression psychosis coma Neuromuscular effects: weakness hypertonia |
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Cardiac effects of hypocalcemia
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Cardiovasuclar effects:
Delayed repolarization, prolonged QT interval |
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Cardio effects of hypercalcemia
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Hypertension
Bradycardia |
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*****Primary hyperparathyroidism and ______ account for 90% of cases of hypercalcemia
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cancer
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Most patients with sporadic primary hyperparathyroidism are who?
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postmenopausal women with an average age of 55 years
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>80% of cases of what are caused by a solitary parathyroid adenoma?
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Primary Hyperparathyroidism
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Surgical Candidacy for PTH treatment
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Serum calcium greater than 1mg/dL above the upper limit of the reference range
24 hour urine calcium greater than 400 mg Creatinine clearance reduced by more than 30% compared with age-matched subjects Bone density at the lumbar spine, hip, or distal radius more than 2.5 SD below peak bone mass Age under 50 Patients for whom medical surveillance is not desirable or possible |
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Medical Management Primary HPT
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1) Estrogen
Dose required is high 2) SERMs Reduction in serum calcium and markers of bone turnover after 4 weeks 3) Bisphosphonates Studies have shown increase in lumbar spine and femoral neck mineral density 4) Calcium/Vitamin D 5) Calcimimetic agents (Cinacalcet) |
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Diagnosis of Secondary HPT
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Elevated PTH in the setting of low or normal serum calcium is diagnostic
If phosphorous is elevated, cause is renal If phosphorous is low, other causes of vit D deficiency should be sought |
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Prevention of secondary HPT
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Vit D replacement
Phosphorus binders [Sevelamer] |
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Treatment of secondary HPT
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Medical
Calcimimetic agents Surgical Considered in cases of refractory severe hypercalcemia, severe bone disease, severe pruritis, calciphylaxis, severe myopathy |
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Calcimimetics Suppress PTH secretion without elevating serum calcium and phosphorus levels
Increase sensitivity of the CaSR to ______ |
extracellular Ca ions
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Calcimimetic (PTH secretion inhibitor)
effect on PTH, Ca, and PO4 |
PTH down
Ca down PO4 down |
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Vitamin D analogue (PTH synthesis inhibitor)
effect on PTH, Ca, and PO4 |
PTH down
Ca up PO4 up |
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Doxercalciferol and ________ have recently been approved for the treatment of secondary hyperparathyroidism in patients with renal failure
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paricalcitol
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If your thyroid gland is removed, will your Ca levels be altered?
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no
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What about calcitonin being lost with thyroidectomy?
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it's minor
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Calcitonin inhibits ______ bone resorption & in the kidney,
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osteoclastic
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calcitonin reduces both calcium and phosphate reabsorption as well as reabsorption of other ions, including sodium, potassium, and ______
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magnesium
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how is salmon calcitonin administered?
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Intranasal
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Calcitonin Secreted by the __ cells of the thyroid gland
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"C" or "parafollicular"
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Calcitonin Inhibits _______-mediated Ca2+ mobilization
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osteoclast
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Calcitonin: Clinical uses
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For treatment of severe hypercalcemia
For treatment of osteoporosis Paget’s disease |
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Calcitonin: adverse effects
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Nausea
Facial flushing Swelling of the hands Inflammatory reactions at injection sites Urticaria Up to 20 % of patients treated with salmon calcitonin develop resistance |
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Glucocorticoid hormones alter bone mineral homeostasis by _________ vitamin D―stimulated intestinal calcium transport, by stimulating renal calcium excretion, and by blocking bone formation
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antagonizing
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Prolonged administration of glucocorticoids is a common cause of _______ in adults and stunted skeletal development in children.
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osteoporosis
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the principal therapeutic application for estrogen administration in disorders of bone mineral homeostasis is the treatment or prevention of ________
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postmenopausal osteoporosis.
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Widely used phosphate binder:
a) Aluminum-containing b) Calcium-containing c) Sevelamer |
b) Calcium-containing
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No longer used phosphate binder:
a) Aluminum-containing b) Calcium-containing c) Sevelamer |
a) Aluminum-containing
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Phosphate Binders (Ca-based) effect on PTH, Ca, and PO4?
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PTH down
Ca up PO4 down |
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Causes of hypocalcemia
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Malabsorption states
Inadequate diet Hypoparathyroidism Renal disease Vitamin D deficiency |
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Bones are composed of cortical and ____ regions
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trabecular
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Osteoblasts
Form new bone. 10-20% become ______ |
osteocytes
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Osteocytes
Sense _______ changes. 25,000/mm3 |
mechanical
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Stromal cells
Produce growth factors for haemopoesis Help osteoclasts to form Differentiate to form ______ |
osteoblasts
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Bone remodeling Regulation by osteoblast RANKL and OPG. What are those?
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RANK - receptor for activator
of nuclear factor-kB RANK ligand (RANKL) OPG- osteoprotegrin, a neutralizing soluble receptor that blocks RANK activity |
