Sweatman: NSAIDs and ARF

Question 1

Regarding glomerular filtration, what is normal GFR in a 70kg, 20 year old healthy man?

Answer 1

120 mL/min

Question 2

T or F: only unbound drug in plasma water is excreted by glomerular filtration

Answer 2

T

Question 3

What type of transportation systems does tubular secretion involve? Are these transport systems specific for substrates?

Answer 3

organic anion (OATs, OATPs, MRPs) 
organic cation (OCTs, MDR/1, P-gp)

No, there is overlapping substrate specificities so there is a potential for drug-drug interactions

Question 4

Tubular secretion can be ____ rate limited or ____ rate limited

Answer 4

perfusion rate limited

capacity rate limited

Question 5

What is perfusion rate limitation in terms of tubular secretion?

Answer 5

the extraction ratio is not limited to the unbound fraction of drug

Question 6

what is capacity rate limited in terms of tubular secretion?

Answer 6

the extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in RBCs

Question 7

T or F: tubular reabsorption is largely an active process for the majority of drugs and drug metabolites

Answer 7

F, passive

Question 8

What is the driving force of tubular reabsorption?

Answer 8

reabsorption of filtered water

Question 9

what transporters are expressed on the apical membrane of epithelial cells and mediate tubular reabsorption of drugs? What kind of drugs do they transport?

Answer 9

Peptide transporters (PEPT1, PEPT2)

peptide like drugs: B-lactams and ACE inhibs

Question 10

T or F: renal function declines with age irrespective of the use of drug therapy

Answer 10

T

Question 11

T or F: use of NSAIDs is respobsible for 15.4% of preventable adverse drug events

Answer 11

T

Question 12

T or F: prostaglandin (PG) synthesis is a primary regulator of renal function

Answer 12

F, it is of minimal importance in the kidney of healthy individuals with normal volume status

Question 13

Which PGs are the predominant mediators of physiologic activity in the kidney? How do they work?

Answer 13

PGI2 and PGE2

induce vasodilation of interlobular arteries, afferent and efferent arterioles, and glomeruli

Question 14

What pathological states can stimulate PG synthesis?

Answer 14

intravascular volume depletion (vomiting, diarrhea, diuretic therapy)

decreases in RBF (CHF, cirrhosis, nephrotic syndrome)

Question 15

PGI2 and PGE2 can antagonize the local effects of circulating molecules that would normally maintain SBP, what are these molecules?

Answer 15

angiotensin 2, endothelin, vasopressin, catecholamines

Question 16

How can PGs preserve GFR?

Answer 16

by antagonizing arteriolar vasoconstriction and blunting mesangial and podocyte contraction that is induced by endogenous vasopressors (AT2, endothelin, AVP)

Question 17

What happens when NSAIDs are administered to an individual with underlying kidney disease?

Answer 17

blockage of PG synthesis –> significant reduction in GFR and RBF

Question 18

What increases the risk of renal complications with NSAID use?

Answer 18

age, dose and duration of NSAID use

Question 19

T or F: PG production is decreased in chronic kidney disease (CKD)

Answer 19

F: it is increased, upregulation of PG synthesis is induced by intrarenal mechanisms activated to increase perfusion of nephrons

Question 20

What medications can increase the risk for ARF when used in combination with NSAIDs?

Answer 20

meds that block the RAAS:
ACE inhibitors
ARBs

Question 21

T or F: PGs play an important role in the loop of Henle and distal nephron

Answer 21

T

Question 22

What does PGE2 do in the TALH and CD?

Answer 22

decreases cellular transport (reabsorption?) of NaCl –> increased renal Na+ excretion and decrease in medullary tonicity

Question 23

How do PGE2 and PGI2 affect the JG apparatus?

Answer 23

stimulate secretion of renin –> increased angiotensin 2 and aldosterone –> enhanced Na+ retention and K+ excretion in distal nephron

Question 24

How do PGE2 and PGI2 affect water balance?

Answer 24

they inhibit cAMP synthesis and oppose the action of ADH, thereby facilitating water excretion

Question 25

What is the net effect of chronic NSAID consumption?

Answer 25

mild, dose-dependent increase in BP

Question 26

What patient populations are at a higher risk to develop HTN when given NSAIDs?

Answer 26

older
pre-existing HTN
salt-sensitive
renal issues
renovascular HTN

Question 27

T or F: COX-2 inhibitors are essentially equivalent to other classes of NSAIDs with respect to their nephrotoxic potential

Answer 27

T

Question 28

How is acute toxicity to NSAID tx manifested?

Answer 28

tubular epithelial necrosis secondary to altered renal hemodynamics

Question 29

An allergic reaction to NSAIDs can lead to ___

Answer 29

interstitial nephritis