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80 Cards in this Set
- Front
- Back
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collagen gives what to a bone? minerals do what to a bone?
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collagen gives bone flexibility
minerals (ca2+ and p+) gives stiffness and strength |
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bone remodeling reaches a max at what age
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20-25 yo
balance between resorption and bone formation |
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what are some factors of bone remodeling
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80% bone remodeling has genetic predisposition 20% is modifiable
facotrs = caffeine, ca2+ intake, smoking, alchol, lack of exercise, estrogen |
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what is composite tissue composed of
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cells, water, matrix, mineral
minerals= crystalline calcium phosphate. carbonate, fluoride, acid phosphate, magnesium, citrate |
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what does hypocalcemia lead to
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unlocking of ca2+ in bone to try to maintain plasma ca2+ level so bone resorption increases
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what is the normal range of plasma ca2+
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9-11 ng/dl
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what organs are involved in bone metabolism/homeostasis
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GI- absorption of ca2+, gut expresses ca2+ binding protein
kidney- reabsorption of ca2+ AND activation of vit D. (PTH activates vit D in kidneys. final step) Extracellular ca2+ and phosphorous- PTH unlocks ca2+ from bone to stabilize extracellular ca2+ levels |
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normally we have 9-11 ng/dc calcium in our body. if it is decreased, what occurs
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increase PTH so there is increased bone resorption
pure role is to unlock ca2+ from bone and increase bone resorption to increase extracellular plasma ca2+ anytime plasma ca2+ level falls below 7 |
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T or F vit D can work by itself without extra help from organs
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false.
needs to be activated by liver to hydroxy vit D, then final step of activation occurs via PTH in the kidney to 1, 25 dihydroxy vit D (aka calcitriol) which then binds to receptors and upregulates ca2+ absorption in the gut thats why renal or hepatic failure often results in hypocalcemia |
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what are the roles of osteoblasts, cytes, and clasts
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osteoblasts- make bone matrix (mineralization)
cytes- regulate nutritional uptake clasts- remove bone (resorption) anytime plasma ca2+ low and PTH high, you are activating osteoclasts BMD is related to serum calcium levels |
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osteoporosis is a dz of what?
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osteoclasts
increased osteoclastic activity --> bone breakdown |
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what is the role of PTH and vit D
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PTH = bone resorption
vit D= bone formation and mineralization (hardening of the bone) absorption of ca2+ and phosphorus in GI tract |
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what are the roles of PTH
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increase (bone remodeling) serum ca2+ via unlocking ca2+ from bone to increase plasma ca2+ and activates vit D in final step 1, 25 dihydroxy vit D (calcitriol) in the kidneys
increases excretion of inorganic phosphate, increases tubular reabsorption of calcium |
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what is the role of vit D
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useless by itself, must be activated by PTH
increases GI absorption of calcium and phosphate augments bone mineral mobilization increases renal calcium reabsorption |
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what happens if you have vit D insufficiency
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low vit D --> high PTH --> increased bone turnover mediated by PTH --> bone mass/mineral density goes down , cortical porosity increases --> hollow bone, high risk of fractures
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in low levels of vit D what happens to the bone strength?
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vit D is needed to absorb ca2+. w/ vit D deficiency, ca2+ absorption decreases to 10-15%. ca2+ reservoir of bone is depleted in attempt to correct for low calcium absorption in gut and bone becomes less dense
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how can you get more vit D?
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salmon, tuna, UV rays from sun is main way
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which dz is a/w insufficiency ca2+ absorption and decreased bone strength
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chronic kidney dz --> imbalance in PTH --> failure to activate vit D --> insufficient ca2+ absorption --> brittle bones
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what is the role of calcitonin
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inhibits osteoclast activity and osteolysis
it is released anytime there is excessive plasma ca2+ >11 ng/dl role is to reduce ca2+ absorption and increase renal excretion therefore it locks ca2+ into bone secretion is stimulated by gastrin |
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when do ssx of hypercalcemia manifest? hypocalcemia?
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>15 ng/dl plasma ca2+, <7 ng/dl
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how does calcitonin affect bones? how does PTH affect bones?
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calcitonin (released from thyroid glands) decreases ca2+ absorption and stimulates calcium salt deposit in bone . osteoclasts inhibited while osteoblasts continue to lock ca2+ ions in bone matrix
PTH (released from parathyroid glands) stimulates osteoclasts to degrade bone matrix and release ca2+ into blood |
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what is the role of 1, 25 dihydroxy vit D3
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activated in liver, final activation in kidney via PTH
reabsorption of calcium in intestine absorption of calcium in GI tract |
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what are the main causes of HYPERcalcemia
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increased bone resorption
increased GI absorption decreased elimination by kidneys |
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what is VITAMINS TRAP
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reasons for hypercalcemia
vitamin D intoxication, immobilization, thyrotoxicosis, addisons, milk alkali, infection, neoplasms, sarcoidosis, thiazides, rhabdo, aids, parathyroid/pheochromocytoma/pagets |
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what are some clinical presentations of hypercalcemia
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fatigue
mental confusion anroexia polyuria/polydipsia cardiac conduction abnormalities constipation nephrolithiasis and ca2+ depositions in blood vessels |
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how do you treat hypercalcemia
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volume expansion (rehydration because hypercalcemia pt has been vomiting) with normal saline
increase calcium excretion using loop diuretics as adjunct to volume expansion (furosemide acts on thick ascending loop of henle to knock out na-k pump so you lose ca2+) short term rx with CALCITONIN in CHF and renal dysfunction patients because you dont want volume expansion in pt with CHF |
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this the DOC for long term treatment of hypercalcemia and is contraindicated in renal insufficiency
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pamidronate 30-90 mg IV 2-24 hrs
inhibition of bone resorption and formation of mature osteoclasts using bisphosphanates can't use in renal insufficiency because drugs will accumulate |
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what is a cause of HYPOcalcemia
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mutation in PTH (change in aa sequence) that decreases the effect of PTH and vit D on bone, gut, and kidney
PTH can't activate vit D and then that downregulates ca2+ binding protein |
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what does plasma pH have to do with HYPOcalcemia
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increase plasma pH will increase ca2+ binding to albumin so less free ionizable ca2+ available
therefore alkalosis can cause hypocalcemia by locking ca2+ to albumin |
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primary causes of HYPOcalcemia
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hypoparathyroidism - absent PTH
ineffective PTH reduced dietary vit D chronic kidney dz lower pH |
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low calcium will have what kind of clinical sx?
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muscle spasms, tetany
seizure resp arrest laryngeal spasm irritability |
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what is the treatment of hypocalcemia
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calcium gluconate DOC for parenteral pathway because it has minimal irritaiton to veins
calcium chloride oral calcium : calcium carbonate and calcium lactate calcitriol can be given, but must give active form of vit D to renally impaired pts all pts require acidic pH for ca2+ absorption |
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which drug is the only one that does NOT require acidic environment for absorption?
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calcium citrate
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what do you give a geriatric pt with peptic ulcer on PPI that requires ca2+ supplements?
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calcium citrate.
PPI will make the environment basic (not acidic) usu all other drugs will need acidic environment for absorption. calcium citrate will be the only one that works |
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what are some characteristics of osteoporosis
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reduction of bone density
increased resorption reduced calcium drug induced (corticosteroid) osteoporosis post menopausal women and men <65 have higher risk BMD goes down but pts don't realize it --> >50% dxed w/ osteoporosis after first fx (hip, vertebrae) |
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some causes of osteoporosis are what?
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age related
hypogonadism chronic glucocorticoid administration (increase amount and activity of osteoclasts and downregulate ca2+ binding protein in GI tract so this reduces ca2+ absorption) calcium deficiency |
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what is the path behind osteoporosis and post menopause women
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estrogen directly regulates osteoblast via increasing markers of osteoblast differentiation
estrogen decreases number of osteoclasts and increases the production of anti resorptive factors (IGF-1) when estrogen goes down, there will be increased RANKL--> osteoclast and bone turnover, increase IL1-IL-6, TNF --> increase bone resorption and decrease antiresorptive factors. ALL LEAD TO BONE BREAKDOWN |
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what are some sx that come along with osteoporosis
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bone pain, loss of height, kyphosis
usu dx via DEXA of hip, spine |
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what is the normal BMD, osteopenic BMD, and osteoporosis BMD?
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normal 1SD of a young adult
osteopenia 1-2.5 SD < young adult osteoporosis >2.5 SD < young adult - hollow bone, brittle, susceptible to fracture; loading ca+ and vit D now is NOT going to help, need prophylaxis |
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when does the bone mass max out at?
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20-25
need to do weight bearing exercise before 30 to prevent osteoporosis |
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where is paget's disease usu confined to
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knee
skull pelvis clavicle increased bone remodeling but it is so rapid that collagen is hardly ever laid down or it is down so in an erratic fashion --> bowing of knees and significant inflammation that requires analgesia |
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why does Paget's dz has an increased incidence of CHF?
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dt erratic rapid bone formation, it requires angiogenesis so heart has to work harder to pump blood to new bone, wears it out, and causes volume overload
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what are some agents that affect calcium homeostasis
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teriparatide
calcitonin (hypercalcemia in CHF pts because they can't do voluem expansion + loop diuretics) ergocalciferol doxercalciferol calcitriol |
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a patient is on chronic glucocorticoid rx, what shoudl they also receive to prevent osteoporosis?
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alendronate (prototype bisphosphanate) (prevent bone loss )
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how does cinacalcet work
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it mimics ionized free ca2+ by allosteric activation of ca2+ sensing receptor so this slows down teh release of PTH and loweres bone resorption
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cinacalcet is indicated for what
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secondary hyperparathyroidism dt renal failure or PTH carcinoma
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what is the frist line tx of osteoporosis always?
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bisphosphonates
reduce proliferation of osteoclasts and upregualtes osteoblasts anti-resorptive action- inhibitory action on osteoclasts reduces osteoclastic bone resorption decreases formation of osteoclasts inhibition of osteoclastic proton pump increases osteoclastic apoptosis |
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why is alendronate also given with bisphophonates
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bisphosphanates have very poor bioavailability and very poor oral absorption
alendronate given parentally on a weekly/monthly basis to reduce oral administration route |
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what are the indications for bisphosphanates
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first line rx for osteoporosis
osteoporosis prevention particularly in post menopausal women and from chronic glucocorticoid use osteolysis a/w tumor hypercalcemia |
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what are some adverse effects of bisphosphanates
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MUST AVOID ORAL ROUTE IN PTS WITH PEPTIC ULCERS dt esophageal and gastric irritation GI bleeding
diarrhea nausea CONTRAINDICATED in renal compromised fxn because they will accumulate and cause renal toxicity, peptic ulcer dz |
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what should you tell your patients to take or do when taking oral bisphosphonates
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take it with lots of water and stay upright for at least 30 min afterwards
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what is the function of calcitonin
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antagonizes PTH effects
decreases ca2+ in serum and deposits it into bone binds to osteoclasts, alters calcium passage inhibits bone turnover in paget's dz |
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when is calcitonin used as an adjunct
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hypercalcemic emergencies it is given via nasal spray or parentally
for hypercalcemic pts with CHF because they can't do volume expansion also given as an adjunct in paget's |
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how is calcitonin adminsitered
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SC or IM
metabolized in kidneys cautious use in renal impairment CI in hx of allergies (salmon) |
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what are some adverse effects that usu happen w/ initial dose but subsides after
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HA
weakness nausea vomiting |
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this is indicated ONLY in advanced and multiple neoplasms that cause hypercalcemia
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plicamycin (mithracin)
inhibits hypercalcemic action of vit D inhibits effects of PTH on osteoclasts high toxicity low rx index limited clinical use- only as a single dose under strict clinical monitoring |
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what are the CI for plicamycin
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electrolyte imbalance
myelosuppression pregnancy bleeding disorders cautious use in hepatic and renal dysfxn (need to reduce dose) |
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what do you give for pts with renal compromise
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active form calcitriol
increases intestinal calcium and phosphorous absorption decreases renal excretion of those 2 increases plasma ca2+ and phos levels may increase bone formation |
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what are the clinical indications for vit D?
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rickets - prophylaxis and cure
osteoporosis - prevention and tx osteomalacia >1000 mg of vit D/day in 3 doses always required |
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what type of vit D prep is really expensive and reserved for renally impaired pts?
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1,25 dihydroxyvit D3 (calcitriol)
active vit D |
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what is teh function of calcitriol
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increases absorption of calcium in the GI tract, increases renal calcium reabsorption, elevation in plasma calcium, reduces PTH levels, reduces bone resorption
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what are the indications for vit D preps/calcitriol
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hypocalcemic patients
patients with hypoparathyroidism well absorbed from GI tract 3-5 days metabolized in liver |
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when are you contraindicated for vit D preps/calcitriol
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hypercalcemia and pts on digoxin because it can exacerbate effect of cardiac glycosides so you need to lose the dose of calcitriol
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what is ergocalciferol?
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it is essentially the same as calcitriol but it needs activation
calcitriol is an already active form of vit D |
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ergocaliferol is indicated for what
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hypophosphatemia
osteomalacia osteoporosis prophylaxis and treatment of rickets well absorbed but very slow acting because it needs to be activated to calcitriol before exerting its effect |
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where is ergocalciferol absorbed from and where is it metabolized to active metabolites? how long does it last
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absrobed from GI tract
metabolized in kidney max activity seen 3-4 weeks after duration for 2 months |
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what is doxercalciferol
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vit d2 analog
undergoes LIVER activation unlike ergocalciferol which is activated in kidney increases absorption of calcium in GI tract |
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what is doxercalciferol indicated for
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hyperparathyroidism - reduction of PTH
cautious use in renal or hepatic dysfxn and in pregnancy |
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name a calcimimetic
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cinacalcet
mimics effects of ionized calcium on calcium sensing receptor of teh parathyroid gland --> increased sensitivity to calcium --> reduction of PTH secretion used as an adjunct in hypercalcemia in parathyroid carcinoma to reduce secretion of PTH |
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what is the t 1/2 for cinacalcet
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30-40 hrs
highly bound to plasma proteins |
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how do you tx pt w/ osteoporosis that is now failing bisphosphonate rx after 18 motnhs of use (DEXA scan shows BMD has dropped again) OR which drug directly stimualtes new bone formation
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teriparatide
has first 30 a.a. of PTH but stimulates osteoblastic activity and new bone formation. if you keep bombarding pt with PTH it'll cause boen resorption, but if you give PULSATILE doses infrequently, PTH will cause new bone formation --> TERIPARATIDE acts like pulsatile PTH so it increases bone formation |
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when is teriparatide indicated? and how is it given?
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parenterally
indicated in osteoporosis in women and men, reduces risk of fractures |
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how do you manage osteoporosis pharmacologically?
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calcium 200-1500 mg/day
vit d2 or d3 200-1000 units/day bisphophonates : DOC- alendronate 5 mg daily (prevention) and 70 mg weekly (treatment) risedronate : 5 mg daily, 35 mg weekly ibandronate: 2.5 mg daily 100-150 mg monthly, 3 mg IV every 3 months |
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why do you have to give all of those drugs for osteoporosis
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intervention with bisphosphonate alone is not enough
need calcium and vit D supplements too alendronate is DOC in chronic GC to prevent osteoporosis |
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what is raloxifene
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selective estrogen receptor modulators- given to post menopausal osteoporosis pts. acts like agonist in bone, reduces RANKL expression so increases osteoblast activity
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how is calcitonin given
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intranasally
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teriparatide is given only if what
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20 mcg SC daily only if bisphosphonate is failing
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why can teriparatide not be used beyond 21 months?
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it can cause osteosarcoma
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on top of alendronate being DOC for chronic GC use, it is also DOC for what other dz?
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pagets
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what drugs do you give for pagets?
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calcitonin and alendronate (doc for pagets) bisphosphonate
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