05.20 - Drugs and Renal Fxn (Sweatman) Flashcards
2 peptide-like drugs
beta-lactams, ACEi’s
Though inward conductance is greater than outward, K efflux does not occur b/c
Vm is more positive than EK
What provides driving force for K excretion in DT epithelial cells
Na absorption –> Depolarizes membrane
Tx for hyperkalemia is required if
EKG changes
What mediates reabsorption of peptide-like drugs
Peptide Transporters (PEPT1, PEPT2)
Capacity rate limited
Extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in RBCs
NSAID use in CKD will cause
Acute reductions in renal bloodflow and GFR
PGI2/PGE2 preserve GFR by antagonizing arteriolar vasoconstrictors and
blunting mesangial and podocyte contraction
Drugs that antagonize ___ increase risk of AKI when NSAID is administered
Drugs that antagonize RAAS
Effect of PG’s on RAAS
Stimulate Renin secretion –> Enhance Na retention and K secretion
Effect of PG’s on ADH
Inhibit cAMP synthesis and oppose ADH –> Water excretion
What provides driving force for reabsorptio of drugs and drug metabolites
Extensive reabsorption of filtered water
Why doesn’t K efflux thru ROMK at physiological intracellular Mg
Intracellular Mg binds ROMK and blocks K efflux
T/F: PGs are a primary regulator of renal function
False, minimal importance in kidney of health individuals with normal volume status
What can be used to remove K+ in patients with renal failure
Dialysis
Low magnesium can exacerbate ___ by ___
K wasting by incr K secretion in DT
Most common cause of drug-induced hypokalemia
Anti-infective agents
Effect of PGI2 and PGE2 in kidney
Vasodilation of interlobular arteries, afferent and efferent arterioles, and glomeruli
Effects of PG’s on LOH and Distal Nephron
(1) Incr renal Na excretion, decr medullary tonicity; (2) Stimulate Renin secretion; (3) Inhibit cAMP and oppose ADH
Acute NSAID toxicity is manifest in terms of
Tubular Epithelial Necrosis secondary to altered renal hemodynamics
Anti-infective agents commonly cause what electrolyte abnormality
HypoKalemia
Diureti-induced hypokalemia is associated with
Mild-Moderated Metabolic Alkalosis
2 commonly used formulas that estimate GFR
Cockroft-Gault; MDRD
Effect of PGE2 on cellular transport of NaCl
Decreases cellular transport of NaCl –> Increase Na excretion and decr in medullary tonicity
Kidney PGs have their major role in
preservation of renal fxn when pathologic states supervene and compromise physiologic kidney processes
3 steps in hyperkalemia tx
(1) Calcium Gluconate, (2) Shift to intracellular, (3) Removal of excess K+
Risk of NSAID-associated AKI in health persons
Low, b/c PG production is low in healthy persons
Second most common cause of drug-induced hypokalemia
Diuretics
Net effect of PG actions on LOH and Distal Nephron is that chronic NSAID consumption can lead to
a mild, dose-dependent increase in BP
Tubular secretion occurs primarily in
pT
GFR > ___ is normal
80
At physiological intracellular Mg concentration, ROMK conducts K in which direction
Inward
Perfusion rate limited
extraction ratio is not limited to the unbound fraction of drug
COX-2 inhibitor effects on kidneys
equivalent to other classes with respect to their nephrogenic potential
NSAIDs are also associated with interstitial nephritis that is thought to be result of
Allergic reaction
GFR < ___ is severe renal impairment
30
3 conditions with increased prevalence that are exacerbated by GFR
HTN, CHF, Renal insufficiency
Organic anion and cation transporter systems, w/ overlapping specificities, allow potential for
Drug-Drug interactions
How does insulin lower hyperkalemia
Stimulates Na/H exchange –> Na in –> Stimulates Na/K –> Uptake of K into cell
PG production is increased in ___ disease
chronic kidney disease
Leading causes of drug-induced hyperkalemia
Aldosterone antagonist/k-sparing agents and ACEi/ARB
___ locally mediate effects of both systemic and locally produced vasoconstrictor hormones
Eicosanoids
K secretion in DT is under regulation of
intracellular Mg
3 effects of Calcium in HyperKalemia
(1) Less neg resting Vm; (2) Shift upwards and right of Vm x Vmax curve; (3) Reverses depressed conduction
Action of Albuterol tx of Hyperkalemia
Activates Na/K –> Na leaving forces K in
2 “situations” when PG’s play role in preserving renal fxn
True intravascular volume depletion; Effective decrease in renal blood flow
Surge in catecholamines is often associated with what electrolyte change
Hypokalemia
With no Mg and normal K concentrations, the chemical gradient drives K in which direction?
Outward
2 drugs commonly used to tx Hyperkalemia
B2 agonist (Albuterol) and Insulin
Insulin stimulates what transporter
Na/H exchange (Na in, H out)
PGI2/PGE2 antagonize
local effects (vasoconstriction) of circulating Ang2, Endothelin, Vasopressin, and Catecholamines (that would normally maintain systemic pressure at expense of renal circulation)
What aspect of tubular secretion allows for drug-drug interactions
Transporters with overlapping substrae specificities
