Renal Pharm Flashcards
what are some agents that cause acute kidney injury? what is it often a complication of?
antibiotics, chemotherapy, radiocontrast dyes. thoracic surgery.
what are the main mechanisms of acute kidney injury?
renal ischemia/reperfusion; mismatch between oxygen consumption and supply, renal tissue hypoxia and tubular necrosis and apoptosis
what are the 5 categories of emerging agents, with examples?
anti-apoptotic (caspase inhibitors, minocycline), anti-inflammatory (adenosine agonist, phosphatidylserine binding protein), anti-sepsis (insulin), growth factors (recombinant epo), vasodilators (fenoldopam, ANP)
basic treatment for CKD?
RAAS inhibitors
what do RAAS inhibitors do for CKD?
decrease progression of albuminuria, decrease progression of GFR decline, decrease risk of ESRD
what do NSAIDs do with CKD?
further damage. may interact with ACE and ARBs
what is treatment for diabetic nephropathy?
manage primary disorder: good glycemic control, BP control, minimize proteinuria
what is a new drug that might combat kidney disease?
bardoxolone (initially anti-cancer)
what analogs may also become useful?
EET analogs
how does erythropoietin work?
hormone produced in kidney, regulates RBC production by reducing apoptosis and stimulating differentiation and proliferation of erythroid progenitor cells. released in response to hypoxia in endothelial cells of periutubular caps.
symptoms of anemia in CKD? causes?
fatigue and decreased cognition. d/t epo deficiency in ESRD.
how is epoetin given? pharmacodynamics?
IV (rapid response) or sub q (greater response). half life: 4-6 hours. given 2-3 times/wk
epoetin SE?
N/V/D, HA, flu-like stx early, HTN (dose dependent, can be severe), thrombosis of arteriovenous shunts
epoetin SE with renal failure?
pure red cell aplasia subcutaneous admin in renal failure is assoiated with ab formation: must discontinue treatment
what hormones regulate plasma calcium?
parathyroid hormone, calcitonin, calcitriol
how much of calcium is free ionized?
50 percent
what state favors ionization? disfavors it?
acidosis favors ionization. alkalosis disfavors it.
what happens to calcium and phosphate in kidney failure?
decreased renal excretion of phosphate, diminished production of calcitriol
what hormone increases serum calcium levels?
calcitriol
what state occurs with increased phosphate and reduced calcium?
secondary hyperparathyroidism
what is the hallmark of secondary hyperparathyroidism?
increased PTH
what three factors lead to increased PTH?
decreased production of vitamin D3 (calcitriol), decreased serum calcium, increased serum phosphorous
mechanism of calcitriol/analogs
increased absorption of Ca and PO4 from intestine, resorption of Ca and PO4 from bone, enhanced renal tubular reabsorption of Ca
unwanted effect of calcitriol analogs?
excessive dosing leads to hypercalcemia
signs of 1,25 hydroxy D deficiency in CKD?
fractures (especially elderly), hyperparathyroidism (secondary)
what are some phosphate binders?
calcium carbonate, calcium acetate, lanthanum carbonate
what is a calcium and aluminum free phosphate binder? structure?
sevelamer: Ca and Al free polymeric structure
SE for sevelamer/phosphate binders?
GI side effects, hypercalcemia
first generation bisphosphonate? third generation?
etidronate. zoledronate.
how do bisphospohonates work?
pyrophosphate analogs that bind to hydroxyapatite crystals in bone matrix to inhibit bone resorption in bone matrix to inhibit bone resorption
SE of bisphosphonates?
GI disturbances, abdominal pain, nausea, osteonecrosis of jaw (IV)
calcitonin production? actions?
produced by parafollicular or C cells of thyroid gland. secreted when plasma Ca levels rise. lowers plasma Ca by limiting bone resorption and increasing PO4 excretion in urine
calcitonin administration? SE?
IM or sub q. 20 min half life. facial flushing, HA/dizziness, GI (N/V/D), taste disturbance.
how does colchicine help in gout in CKD?
inhibits PMNs. oral. reduces inflammation, given every 6-12 hrs to relieve stx.
SE of colchicine?
GI toxicity, rash
what are the xanthine oxidase inhibitors?
allopurinol, febuxostat.
how do XO inhibitors work?
competitive enzyme inhibitors with variable half life (b/c renal excretion)
SE of XO inhibitors?
GI upset, risk of acute gout (release of uric acid from tissue deposits), hypersensitivity to allopurinol (rashes, esp in renal dz)
what drug interaction occurs with allopurinol?
azathioprine
what is the urate oxidase analog?
rasburicase. recombinant version of enzyme urate oxidase.
rasburicase use? SE?
prophylaxis during chemo (can be used in CKD). SE: fever, N/V/D. hypersensitivity, hemolysis (due to hydrogen peroxide production as a by product)
calcineurin inhibitors?
cyclosporine, tacrolimus
MOA for cyclosporine? tacrolimus?
cyclosporine: binds cyclophilin
tacrolimus: binds FKBP12
complex binds and inhibits action of calcineurin. inhibits cytokine transcription (eg IL2) needed for T-cell activation and proliferation
