110414 renal pharm

Question 1

high incidence of acute kidney injury occurs in what cases?

Answer 1

in pts receiving antibiotics, chemo, or radiocontrast dyes

common complication also of thoracic surgery

Question 2

mechanism of acute kidney injury

Answer 2

arterial occlusion, hypotension, shock

renal ischemia-reperfusion

microvascular dysfxn
excess vasoconstriction
inflam, oxidative stress
endothelial injury
endothelial-leukocyte interactions

mismatch btwn O2 consumption and O2 supply

renal tissue hypoxia

tubular necrosis and apoptosis

Question 3

most common causes of chronic kidney disease

Answer 3

diabetic nephropathy

HTN

Question 4

tx for chronic kidney disease

Answer 4

inhibitors of renin angiotensin system

Question 5

effect of renin angiotensin inhibitors in CKD

Answer 5

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

the beneficial effects of them are independent of BP and blood glucose control

Question 6

what do you want to avoid with tx for CKD?

Answer 6

NSAIDs-they damage the kidneys further. may interact with ACEi and ARBs

Question 7

CKD mainly causes hypo or hypercalcemia?

Answer 7

hypo, but can have hypo or hypercalcemia

Question 8

plasma calcium is regulated by

Answer 8

PTH, calcitonin, calcitriol (active vit D)

Question 9

kidney failure-what happens to phosphate and calcitriol?

Answer 9

decreased GFR leads to decreased renal excretion of phosphate and diminished production of calcitriol, both leading to decreased Ca in blood and increased PTH

Question 10

what leads to increase in PTH in secondary hyperparathyroidism in kidney disease?

Answer 10

decreased production of vit D3 (calcitriol)
decreased serum Ca
increased serum phosphorous

the above 3 are due to decrease in kidney fxn associated w chronic kidney dis

Question 11

MOA of calcitriol and vit D analogs

Answer 11

enhance absorption of Ca and PO4 from intestine (by increasing synthesis of Ca ch and a carrier calcium binding protein)

calcitriol also enhances recruitment and differentiation of osteoclast precursor for remodeling–resorption of Ca and PO4 from bone

also enhances tubular reabsorption of Ca

Question 12

adverse effect of calcitriol and vit D analogs

Answer 12

excessive dosing leads to hypercalcemia

Question 13

phosphate binders

Answer 13

react with phosphate in GI tract and form an insoluble compound

Question 14

when can hypercalcemia occur?

Answer 14

with prolonged kidney disease

renal transplant pts can have parathyroid hyperplasia and then, restoration of renal fxn and calcitriol production can lead to hypercalcemia

Question 15

what can be used to treat hypercalcemia?

Answer 15

bisphosphonates

Question 16

bisphosphonates MOA

Answer 16

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

Question 17

calcitonin MOA

Answer 17

lowers plasma Ca by limiting bone resorption

increases phosphate excretion in urine

Question 18

side effects of calcitonin

Answer 18

facial flushing
headache, dizziness
GI
taste disturbance

Question 19

rasburicase

Answer 19

I.V.
recombinant version of enzyme urate oxidase

primarily used as PROPHYLAXIS during chemo (can be used in CKD)

Question 20

calcitonin effect on kidney

Answer 20

increases Ca and PO4 excretion

Question 21

PTH effect on kidney

Answer 21

increases calcitriol and increases Ca reabsoprtion

Question 22

calcineurin inhibitors ex

Answer 22

cyclosporine

tacrolimus

Question 23

MOA of calcineurin inhibitors

Answer 23

bind to cytosolic receptor proteins

cyclophilin (cyclosporine)
FKBP12 (tacrolimus)

complex binds to and inhibits action of calcineurin

inhibits transcription of cytokines such as IL-2 that are essential for T cell activation and proliferation

Question 24

cyclosporine

Answer 24

binds cyclophilin, calcineurin inhibitor

oral or IV

Question 25

side effects of cyclosporine

Answer 25

nephrotoxic

hirsutism

HTN and fluid retention

others

Question 26

drug interactions of cyclosporine

Answer 26

nephrotoxic-NSAIDs, aminoglycosides
CYP3A4 inducers
CYP450 inhibitors

Question 27

tacrolimus

Answer 27

bind FKBP12, calcineurin inhibitor

oral or IV

doesn’t stimulate TGFbeta (doesn’t have excessive vasoconstriction) like cyclosporine does

Question 28

side effects of tacrolimus

Answer 28

pleural and pericardial effusions
cardiomyopathy in children
glucose intolerance

Question 29

monitoring calcineurin inhibitor side effects

Answer 29

hepatotoxicity–liver fxn should be monitored regularly

cardiovascular (HTN, hypercholesterolemia)–fewer tacrolimus treated pts need antiHTN meds, and tacrolimus’ effect on lipid levels is less than that seen with cyclosporine

glucose intolerance

neurotoxicity (more often w tacrolimus)

Question 30

calcineurin inhibitor drugs interactions

Answer 30

nephrotoxic agents (NSAIDs, some antibiotics)–monitor renal fxn

K sparing diuretics (hyperkalemia has been seen)

antacids (may inhibit absorption of calcineurin inhibitors)

statins (increased risk of rhabdomyolysis, bone marrow suppression)

Question 31

use of calcineurin inhibitors has been more in favor of

Answer 31

tacrolimus, b/c of cyclosporine’s side effects

Question 32

sirolimus MOA

Answer 32

binds to FKBP12 (different site than tacromlimus). the complex binds and modulates the activity of mTOR. inhibits cytokine/IL2-induced cell cycle progression from G1 to S phase

Question 33

sirolimus route of administration

Answer 33

oral

Question 34

sirolimus side effects

Answer 34

edema, ascites, tachycardia, HTN
hyperlipidemia
bone marrow suppression
others

drug interactions–drugs that induce cyp3A4, drugs that inhibit CYP450

Question 35

benefits of mTOR inhibitor sirolimus

Answer 35

potent prophylaxis against acute cellular rejection

less vasoconstriction (than cyclosporine)

not associated w acute or chronic renal insufficiency (tacrolimus and sirolimus can cause decline in kidney fxn)

Question 36

mycophenolate mofetil

Answer 36

competitive, reversible inhibition of IMPDH, a critical rate limiting enzyme in de novo purine synthesis. lymphocytes are dependent on de novo pathway vs. salavage pathway utilized by other cell types.

inhibits proliferation of B and T lymphocytes

oral or IV

Question 37

side effects of mycophenolate mofetil

Answer 37

leucopenia, thrombocytopenia, anemia
opportunitistic infec
others

Question 38

azathioprine

Answer 38

purine analogue
metabolized in liver to 6-mercaptupurine and then to thiosinosine monophosphate (TIMP)

TMP decreases synthesis of DNA precursors and also incorporates into DNA

more non-specific effects than mycophenolate mofetil

blocks CD28 co stimulation of T cells

oral

Question 39

side effects of azathioprine

Answer 39

bone marrow suppression, leukopenia, thrombocytopenia

Question 40

comparison of side effects of azathioprine and mycophenolate mofetil

Answer 40

both need to monitor complete blood counts.

GI side effects are more common in mycophenolate mofetil

Question 41

IL-2 receptor antibodies

Answer 41

basiliximab
daclizumab
alemtuzumab

all are antiCD52-IL2 receptor antibodies

Question 42

basiliximab

Answer 42

IV

given immediately prior to surgery and 4 days following

Question 43

belatacept

Answer 43

IV
fusion protein binds CD80 and CD 86 mkolecules. blocks costimulatory action with CD28 on T cell activation

used for renal transplantation in pts SEROPOSITIVE FOR EBSTEIN BARR VIRUS

Question 44

prednisolone

Answer 44

oral

inhibits pro inflammatory transcription factors such as NFkB. other mechanisms too.

Question 45

induction agents ex

Answer 45

monoclonal or polycloncal antibodies given IV immediately after surgery

muromonab
antithymocyte globulin
basiliximab
daclizumab
alemtuzumab
FTY720