Renal Pharm

Question 1

what are some agents that cause acute kidney injury? what is it often a complication of?

Answer 1

antibiotics, chemotherapy, radiocontrast dyes. thoracic surgery.

Question 2

what are the main mechanisms of acute kidney injury?

Answer 2

renal ischemia/reperfusion; mismatch between oxygen consumption and supply, renal tissue hypoxia and tubular necrosis and apoptosis

Question 3

what are the 5 categories of emerging agents, with examples?

Answer 3

anti-apoptotic (caspase inhibitors, minocycline), anti-inflammatory (adenosine agonist, phosphatidylserine binding protein), anti-sepsis (insulin), growth factors (recombinant epo), vasodilators (fenoldopam, ANP)

Question 4

basic treatment for CKD?

Answer 4

RAAS inhibitors

Question 5

what do RAAS inhibitors do for CKD?

Answer 5

decrease progression of albuminuria, decrease progression of GFR decline, decrease risk of ESRD

Question 6

what do NSAIDs do with CKD?

Answer 6

further damage. may interact with ACE and ARBs

Question 7

what is treatment for diabetic nephropathy?

Answer 7

manage primary disorder: good glycemic control, BP control, minimize proteinuria

Question 8

what is a new drug that might combat kidney disease?

Answer 8

bardoxolone (initially anti-cancer)

Question 9

what analogs may also become useful?

Answer 9

EET analogs

Question 10

how does erythropoietin work?

Answer 10

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.

Question 11

symptoms of anemia in CKD? causes?

Answer 11

fatigue and decreased cognition. d/t epo deficiency in ESRD.

Question 12

how is epoetin given? pharmacodynamics?

Answer 12

IV (rapid response) or sub q (greater response). half life: 4-6 hours. given 2-3 times/wk

Question 13

epoetin SE?

Answer 13

N/V/D, HA, flu-like stx early, HTN (dose dependent, can be severe), thrombosis of arteriovenous shunts

Question 14

epoetin SE with renal failure?

Answer 14

pure red cell aplasia subcutaneous admin in renal failure is assoiated with ab formation: must discontinue treatment

Question 15

what hormones regulate plasma calcium?

Answer 15

parathyroid hormone, calcitonin, calcitriol

Question 16

how much of calcium is free ionized?

Answer 16

50 percent

Question 17

what state favors ionization? disfavors it?

Answer 17

acidosis favors ionization. alkalosis disfavors it.

Question 18

what happens to calcium and phosphate in kidney failure?

Answer 18

decreased renal excretion of phosphate, diminished production of calcitriol

Question 19

what hormone increases serum calcium levels?

Answer 19

calcitriol

Question 20

what state occurs with increased phosphate and reduced calcium?

Answer 20

secondary hyperparathyroidism

Question 21

what is the hallmark of secondary hyperparathyroidism?

Answer 21

increased PTH

Question 22

what three factors lead to increased PTH?

Answer 22

decreased production of vitamin D3 (calcitriol), decreased serum calcium, increased serum phosphorous

Question 23

mechanism of calcitriol/analogs

Answer 23

increased absorption of Ca and PO4 from intestine, resorption of Ca and PO4 from bone, enhanced renal tubular reabsorption of Ca

Question 24

unwanted effect of calcitriol analogs?

Answer 24

excessive dosing leads to hypercalcemia

Question 25

signs of 1,25 hydroxy D deficiency in CKD?

Answer 25

fractures (especially elderly), hyperparathyroidism (secondary)

Question 26

what are some phosphate binders?

Answer 26

calcium carbonate, calcium acetate, lanthanum carbonate

Question 27

what is a calcium and aluminum free phosphate binder? structure?

Answer 27

sevelamer: Ca and Al free polymeric structure

Question 28

SE for sevelamer/phosphate binders?

Answer 28

GI side effects, hypercalcemia

Question 29

first generation bisphosphonate? third generation?

Answer 29

etidronate. zoledronate.

Question 30

how do bisphospohonates work?

Answer 30

pyrophosphate analogs that bind to hydroxyapatite crystals in bone matrix to inhibit bone resorption in bone matrix to inhibit bone resorption

Question 31

SE of bisphosphonates?

Answer 31

GI disturbances, abdominal pain, nausea, osteonecrosis of jaw (IV)

Question 32

calcitonin production? actions?

Answer 32

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

Question 33

calcitonin administration? SE?

Answer 33

IM or sub q. 20 min half life. facial flushing, HA/dizziness, GI (N/V/D), taste disturbance.

Question 34

how does colchicine help in gout in CKD?

Answer 34

inhibits PMNs. oral. reduces inflammation, given every 6-12 hrs to relieve stx.

Question 35

SE of colchicine?

Answer 35

GI toxicity, rash

Question 36

what are the xanthine oxidase inhibitors?

Answer 36

allopurinol, febuxostat.

Question 37

how do XO inhibitors work?

Answer 37

competitive enzyme inhibitors with variable half life (b/c renal excretion)

Question 38

SE of XO inhibitors?

Answer 38

GI upset, risk of acute gout (release of uric acid from tissue deposits), hypersensitivity to allopurinol (rashes, esp in renal dz)

Question 39

what drug interaction occurs with allopurinol?

Answer 39

azathioprine

Question 40

what is the urate oxidase analog?

Answer 40

rasburicase. recombinant version of enzyme urate oxidase.

Question 41

rasburicase use? SE?

Answer 41

prophylaxis during chemo (can be used in CKD). SE: fever, N/V/D. hypersensitivity, hemolysis (due to hydrogen peroxide production as a by product)

Question 42

calcineurin inhibitors?

Answer 42

cyclosporine, tacrolimus

Question 43

MOA for cyclosporine? tacrolimus?

Answer 43

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