3. Pharm of Osteoporosis and Gout Flashcards
Osteoporosis Drugs (include calcium/vitD)
Bisphosphonates: alendronate, zolendronic acid
Parathyroid Hormone: teriparatide
Selective Estrogen Receptor Modulator SERM: raloxifene
RANKL Inhibitor: ?
Denosumab
Gout Drugs (including NSAIDs/glucocorticoids)
Microtubule Formation Disrupter: Colchicine
Xanathine Oxidase Inhibitor: Allopurinol/febuxostat
Recombinant Uricase: Pegloticase/Rasburicase
Uricosurics: ? (2)
Probencid
Sulfinpyrazone
Some drugs that increase osteoporosis risks include anticoags, glucocorticoids, methtrexate, chemo drugs, anti convulsants…..
Meow
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?
Calcitonin to increase ca bone deposition, decrease uptake ca in intestines and decrease ca reabsorption in kidney
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?
Vit D Fortified foods (milk/yogurt/cheese)
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?
Calcitonin-Salmon
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?
Alendronate - Bisphosphonates
causes osteoclast apoptosis
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?
Zolendronic Acid
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?
Raloxifene
tamoxifen is a SERm but not used for OP
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?
Teriparatide (PTH1-34)
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?
Denosumab
When RANKL/OPG ratio is high= osteoclasts
When RANKL/OPG ratio is low= no osteoclasts
so decreasing RANKL= dec osteoclasts
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?
Denosumab
Drugs for hypercalcemia include furosemide, glucocorticoids, gallium nitrate, bisphosphonates, inorganic phosphates and edtate disodium…
NAH
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?
Cinacalcet
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?
glucocorticoids relieves pain but may hasten OA progression
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?
Clindamycin
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?
in the medullary insterstitium
note: urate anione is made to uric acid in urine- which is very* poorly soluble
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
YEE
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**
TA DAAA
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?
Uricase** (so we need synthetic uricase then to dissemble uric acid!)
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?
Lesch-Nyhan Syndrome
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?
GFR Falls
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?
uric acid production (diet/xanthine oxidase inhibts/ recombinant uricase)
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?
GLUCOCORTICOIDS
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?
Colchicine
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?
Febuxostat, if this doesnt work then LAST RESORT is biologic = pegloticase
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?
ALLOPURINOL
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)?
Febuxostat
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?
Pegloticase
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?
Rasburicase
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*?
Probenecid and Sulfinpyrazone
Review- Acute Gout Treatment: 1) NSAIDs - naproxen and indomethacin 2) Colchicine 3) Glucocorticoids
yas
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
Pegloticase
