Sweatman: NSAIDs and ARF Flashcards
Regarding glomerular filtration, what is normal GFR in a 70kg, 20 year old healthy man?
120 mL/min
T or F: only unbound drug in plasma water is excreted by glomerular filtration
T
What type of transportation systems does tubular secretion involve? Are these transport systems specific for substrates?
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
Tubular secretion can be ____ rate limited or ____ rate limited
perfusion rate limited
capacity rate limited
What is perfusion rate limitation in terms of tubular secretion?
the extraction ratio is not limited to the unbound fraction of drug
what is capacity rate limited in terms of tubular secretion?
the extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in RBCs
T or F: tubular reabsorption is largely an active process for the majority of drugs and drug metabolites
F, passive
What is the driving force of tubular reabsorption?
reabsorption of filtered water
what transporters are expressed on the apical membrane of epithelial cells and mediate tubular reabsorption of drugs? What kind of drugs do they transport?
Peptide transporters (PEPT1, PEPT2)
peptide like drugs: B-lactams and ACE inhibs
T or F: renal function declines with age irrespective of the use of drug therapy
T
T or F: use of NSAIDs is respobsible for 15.4% of preventable adverse drug events
T
T or F: prostaglandin (PG) synthesis is a primary regulator of renal function
F, it is of minimal importance in the kidney of healthy individuals with normal volume status
Which PGs are the predominant mediators of physiologic activity in the kidney? How do they work?
PGI2 and PGE2
induce vasodilation of interlobular arteries, afferent and efferent arterioles, and glomeruli
What pathological states can stimulate PG synthesis?
intravascular volume depletion (vomiting, diarrhea, diuretic therapy)
decreases in RBF (CHF, cirrhosis, nephrotic syndrome)
PGI2 and PGE2 can antagonize the local effects of circulating molecules that would normally maintain SBP, what are these molecules?
angiotensin 2, endothelin, vasopressin, catecholamines
How can PGs preserve GFR?
by antagonizing arteriolar vasoconstriction and blunting mesangial and podocyte contraction that is induced by endogenous vasopressors (AT2, endothelin, AVP)
What happens when NSAIDs are administered to an individual with underlying kidney disease?
blockage of PG synthesis –> significant reduction in GFR and RBF
What increases the risk of renal complications with NSAID use?
age, dose and duration of NSAID use
T or F: PG production is decreased in chronic kidney disease (CKD)
F: it is increased, upregulation of PG synthesis is induced by intrarenal mechanisms activated to increase perfusion of nephrons
What medications can increase the risk for ARF when used in combination with NSAIDs?
meds that block the RAAS:
ACE inhibitors
ARBs
T or F: PGs play an important role in the loop of Henle and distal nephron
T
What does PGE2 do in the TALH and CD?
decreases cellular transport (reabsorption?) of NaCl –> increased renal Na+ excretion and decrease in medullary tonicity
How do PGE2 and PGI2 affect the JG apparatus?
stimulate secretion of renin –> increased angiotensin 2 and aldosterone –> enhanced Na+ retention and K+ excretion in distal nephron
How do PGE2 and PGI2 affect water balance?
they inhibit cAMP synthesis and oppose the action of ADH, thereby facilitating water excretion
What is the net effect of chronic NSAID consumption?
mild, dose-dependent increase in BP
What patient populations are at a higher risk to develop HTN when given NSAIDs?
older pre-existing HTN salt-sensitive renal issues renovascular HTN
T or F: COX-2 inhibitors are essentially equivalent to other classes of NSAIDs with respect to their nephrotoxic potential
T
How is acute toxicity to NSAID tx manifested?
tubular epithelial necrosis secondary to altered renal hemodynamics
An allergic reaction to NSAIDs can lead to ___
interstitial nephritis
