3. Pharm of Osteoporosis and Gout

Question 1

Osteoporosis Drugs (include calcium/vitD)
Bisphosphonates: alendronate, zolendronic acid
Parathyroid Hormone: teriparatide
Selective Estrogen Receptor Modulator SERM: raloxifene
RANKL Inhibitor: ?

Answer 1

Denosumab

Question 2

Gout Drugs (including NSAIDs/glucocorticoids)
Microtubule Formation Disrupter: Colchicine
Xanathine Oxidase Inhibitor: Allopurinol/febuxostat
Recombinant Uricase: Pegloticase/Rasburicase
Uricosurics: ? (2)

Answer 2

Probencid

Sulfinpyrazone

Question 3

Some drugs that increase osteoporosis risks include anticoags, glucocorticoids, methtrexate, chemo drugs, anti convulsants…..

Answer 3

Meow

Question 4

Calcium homeostasis is via the parathyroid glans in which PTH is released which causes increased calcium reabsorption and vitamin D hydroxylation in the kidneys, increased calcium absorption from intestines and increased calcium reabsorption from the bones to increase the levels of calcium in the blood. When calcium levels are too high the thyroid releases what?

Answer 4

Calcitonin to increase ca bone deposition, decrease uptake ca in intestines and decrease ca reabsorption in kidney

Question 5

Calcium salts can treat mild hypocalcemia- oral or parenteral (on given rapidly to increase in severe hypocalcemia). VitD is NOT calcitriol… ergocalciferol is D2 from plants and cholecalciferol is D3 from sun, Vit D is ONLY in shittake mushrooms and oily fish- usually obtained through what foods then?

Answer 5

Vit D Fortified foods (milk/yogurt/cheese)

Question 6

What is similar to calcitonin synthesized in the thyroid but has longer half life and greater potency, inhibits osteoclasts leading to decreased bone resorption and inhibits renal reabsorption of Ca, used for tx of established osteoporosis NOT prevention, not preffered to treat hypercalemia, but can, either INTRANASAL spray or SC/IM admin, very safe drug?

Answer 6

Calcitonin-Salmon

Question 7

What drug for osteoporosis is a structural analog of pyrophosphate (bone), is incorporated into bone and then inhibits bone resporption by decreasing osteoclsts, DRUG OF CHOICE, for any type of osteoporosis as well as paget dz and hypercalcemia of malignancy, **PO or IV, very safe but SE include **esophagitis - take w lots of water, as well as osteonecrosis of the jaw and atypical femur fractures?

Answer 7

Alendronate - Bisphosphonates

causes osteoclast apoptosis

Question 8

Other bisphosphonates include risedronate (PO), ibandronate (PO/IV), tiludronate (PO), and what drug which is given IV ONCE A YEAR**, so avoids GI problems, but has a higher chance of osteonecrosis of the jaw often occuring after tooth extraction or some other dental procedure in cancer patients, also causes kidney dose dependent damage?

Answer 8

Zolendronic Acid

Question 9

What drug for osteoporosis is a selective estrogen receptor modulator SERM which blocks estrogen effects in breast and uterus but is an agonist* in bone, which is why its used to prevent and treat postmenopausal osteoporosis, also reduces risk for development of estrogen dependent breast cancer, admin orally, increases risk of DVT, PE and stroke, not used during pregnancy, causes hot flashes?

Answer 9

Raloxifene

tamoxifen is a SERm but not used for OP

Question 10

What is a truncated version of PTH made by recombinant DNA, only drug for osteoporosis that increases bone formation**, inc bone resorption by osteoclasts and inc deposition via blasts, but med needs to be PULSED, which allows osteoblastic response to dominate, txs all OP, given once daily via pre filled injection, well tolerated, Ca/Mg/uric acid risk transiently?

Answer 10

Teriparatide (PTH1-34)

Question 11

What drug for osteoporosis is a monoclonal ab RANKL inhibitor which is the receptor activator of nuclear factor kappaB ligand, binding RANKL- decreases the formation and function of osteoclasts, treates OP, 60mg INJECTED q6months SQ, (note: also given to prevent bone mets from solid tumors give 120 q4 weeks), SE: back pain, delay in fracture healing , inc risk of new fractures, osteonecrosis of jaw, increases skin reactions and severe infections?

Answer 11

Denosumab

When RANKL/OPG ratio is high= osteoclasts
When RANKL/OPG ratio is low= no osteoclasts

so decreasing RANKL= dec osteoclasts

Question 12

Tx OP in men: risk factor is hypogonadism so testosterone replacement is important, glucocorticoids and androgen deprivation thereapy for prostate cancer- causes OP, men generally respond to drugs stimiliar to women with bisphosphenates being the drug of choice and what being the alternative?

Answer 12

Denosumab

Question 13

Drugs for hypercalcemia include furosemide, glucocorticoids, gallium nitrate, bisphosphonates, inorganic phosphates and edtate disodium…

Answer 13

NAH

Question 14

What drug for osteoporosis is a calcimimetic drug that binds to calcium sensing receptors on the parathyroid gland, increasing sensitivity to calcium, causing a decrease in PTH secretion, used in primary hyperPTH and secondary due to CKD?

Answer 14

Cinacalcet

Question 15

Osteoarthritis OA management- nonpharm includes weight management, exercise, braces, education, NSAIDs for inflam but contraindicated in CHF/CKD, topical NSAIDs like 1% diclofenac gel or capsaicin, also use duloxetine but see constipation, opioid analgesics (but nah) or injections intraarticularly with hyaluronans (no), platelet rich plasma (new hype) or what?

Answer 15

glucocorticoids relieves pain but may hasten OA progression

Question 16

Osteomyelitis is treated with antibiotics and should be given based on the identification of the pathogens from bone cultures- need to give for 4-6 weeks allowing bone to revascularize after debridement, effect abx include fluoroquinolone, trimethoprim sulfamethoxaozle, rifampin and?

Answer 16

Clindamycin

Question 17

Gout is seen with hyperuricemia, monosodium urate crystal deposition in joints, tophi around joints and seen in helix of ear and parenchymal organs, uric acid kidney stons, and gouty nephropathy which acutely is oliguric or anuric renal failure due to precipitation of uric acid in tubules*, and chonic is due to monosodium urate deposition where?

Answer 17

in the medullary insterstitium

note: urate anione is made to uric acid in urine- which is very* poorly soluble

Question 18

Note: alcohol increases purine synthesis and diuresis and increases urate concentration in the plasma, small metabolically active cells means more DNA RNA ATP which means more purines = inc risk of gout- foods include fish shrimp mussels meat, yeast, organs, nuts peanuts, fruits avacado, beans and tuna

Answer 18

YEE

Question 19

Purine are built on a ribose base and are made into AMP/GMP via 5-phosphoribosyl-1-pyrophosphate (PRPP), AMP is deamidated to produce IMP and IMP and GMP are dephosphorylated and ribose is cleaved from the base to give hypoxanthing and guanine, Xanthine is formed from hypoxanthine by xanthing oxidase and from guanine deamidation, and Xanthine is converted to URIC ACID by xanthine oxidase**

Answer 19

TA DAAA

Question 20

What is used in other species who dont get gout which makes uric acid which is insoluble in humans to make allantoin which is SOLUBLE…. the gene is nonfunctional in humans due to 2 independent mutations during hominid evolution?

Answer 20

Uricase** (so we need synthetic uricase then to dissemble uric acid!)

Question 21

What syndrome is due to deficiency in hypoxanthine guanine phosphoribosyl transferase (HGPRT) which converts hypoxanthine to AMP and guanine to GMP to salvage the purines, leading to profound intellectual disability, self mutilation and SEVERE GOUT?

Answer 21

Lesch-Nyhan Syndrome

Question 22

Gout is either due to uric acid underexcretion (90%) or urate overproduction, underexcretion is mainly due to kidney in which uric acid is filtered out, then reabsorbed, then secreted and reabsorbed and the excreted, if plasma urate conc increase and fractional excretion is less than 10% and or what falls, this can lead to daily excess?

Answer 22

GFR Falls

Question 23

Gout tx includes anti-inflamm drugs acutely to promptly reduce inflamm and pain, or prophylactice to reduce re-occurrences. If recurrences are common you tx with increasing uric acid renal excretion (uricosuric drugs) and or reducing?

Answer 23

uric acid production (diet/xanthine oxidase inhibts/ recombinant uricase)

Question 24

Acute gout management since it is so painful you 1) see if patient can use NSAIDs (naproxen drug of choice, or indomethacin/celecoxib), if no then 2) is colchicine contraindicated, if yes then 3) intraarticular/oral/IV with what if it it multi joint lesions?

Answer 24

GLUCOCORTICOIDS

Question 25

What gout drug is derived from autumn crocus, diffuses into cells to bind tubulin, blocking formation of microtubules, leads to inhibition of leukocyte migration and phagocytosis, used in pt w NSAID tolerance or contraindications, tx is effective for 12-24 hours, oral- contraind in pt w renal/hepatic impairment, VERY COMMON SE: GI distress/diarrhea/vomiting/nausea?

Answer 25

Colchicine

Question 26

Urate lowering treatment of gout first line is allopurinol, if underexcreter with GOOD gfr and NO tophi stones - all urate lowering availble, otherwise if there is BAD GFR with stones use allopurinol, if they are tolerant to the drug (allopurinol) what should be used?

Answer 26

Febuxostat, if this doesnt work then LAST RESORT is biologic = pegloticase

Question 27

What gout drug is a competitive* inhibitor of xanthine oxidase, prevents conversion to urate, allowing excretion of hypoxanthine and xanthine (more soluble), or gout or chemo induced gout, given orally, SE include skin rash, trigger acute gout attack, N/V, hypersensitivity reaction** Stevenjohnson syndrome w inc risk in chinese/thai with HLA B5801?

Answer 27

ALLOPURINOL

Question 28

What gout drug is a non-purine/non-competitive inhibitor of xanthine oxidase, causing excretion of hypoxanthine and xanthine, well tolerated by those who cant tollerate allopurinol*, given orally, generally well tolerated but EXPENSIVE ($384 for 30 tabs)?

Answer 28

Febuxostat

Question 29

What gout drug is a recombinant mammalian uricase attached to methoxy polyethylene glycol, it converts uric acid to the far more soluble allantoin*, used in chronic gout REFRACTORY to treatment, IV q 2weeks, SE include infusion reactions/gout flares, extremely expensive and LAST resort?

Answer 29

Pegloticase

Question 30

What gout drug is a nonpegylated recombinant uricase for prevention of acute uric acid nephropathy due to tumor lysis syndrome in patients with hyigh risk lymphoma or leukemia?

Answer 30

Rasburicase

Question 31

What gout drugs (2) is an organic acid that blocks urate reabsorption more than urate secretion, increasing the fractional excretion of urate, decreasing plasma urate concentration, used to reduce urate levels in UNDERexcretors with GOOD GFR (>60) and with NO stones, given orally, it is sulfur containing so may cause hypersensitivity*?

Answer 31

Probenecid and Sulfinpyrazone

Question 32

Review- Acute Gout Treatment: 1) NSAIDs - naproxen and indomethacin 2) Colchicine 3) Glucocorticoids

Answer 32

yas

Question 33

Prevention of RECURRENT Gout - requires urate lowering via 1) life style changes such as diet and weight reduction and avoiding alcohol 2) drugs such as A)allopurinol B) febuxostat C) probenecid (in good kidney) D)? last resort

Answer 33

Pegloticase