Nephrology Flashcards
Definition: Passive transport from plasma into the renal tubule
Filtration
Definition: when substances in tubule move to plasma
Reabsorption
Definition: active transport of substances from plasma into renal tubule
Secretion
Main process in glomerulus?
filtration
Drugs that work on glomerulus?
NONE
What is the first stop in the nephron?
glomerulus
What controls filtrate formation in the glomerulus?
BP
What is being formed in the glomerulus?
ultrafiltrate
What is contained in the ultrafiltrate at the level of the glomerulus?
- Ions, small particles
- NOT proteins and RBCs
Main process in PCT?
reabsorption; some secretion
What is reabsorbed in the PCT/ percentages?
65% NaCl, K, Mg
85% nahco3
100% glu, AAs
What is secreted in the PCT?
organic acids and bases
Which meds work on the PCT?
CAIs
Adenosine antagonists
First site of reabsorption?
PCT
What is being reabsorbed and secreted in the LOH?
Reabsorption: 15-25% NaCl, K
-Ca, Mg
Secretion: Some K
Which meds work on the LOH?
Loop diuretics
What exact spot on the LOH do loops work?
thick ascending limb of LOH
What is being reabs and secreted in the DCT?
Reabs: 4-8% Na, Cl
Sec: Ca (parathyroid control)
What meds work on the DCT?
Thiazide diuretics
What is being reabs and secreted in the cortical collecting tubule?
Reabs: 2-5% Na
Sec: K* and H+
What meds work on the collecting tubule?
K sparing diuretics, adenosine antagonists
What is being reabs and secreted in the medullary collecting duct?
Reabs: water
Sec: NOTHING
**collecting duct= final conc of urine
What meds work on the collecting duct?
ADH antagonists
List the drugs that are carbonic anhydrase inhibitors
Acetazolamide (oral), dorzolamide, brinzolamide (topical)
MC CAI?
Acetazolamide
the oral CAI is?
Acetazolamide
Topical CAI is?
dorzolamide, brinzolamide
The topical CAIs are used in which body part?
eyes (ophthalmic drops)
CAIs MOA?
Inhibits carbonic anhydrase, which is responsible for dehydrating H2CO3; reduces aqueous humor production
Bicarb buffer system
H2CO3–>
CAIs main effect on the body?
reduce aqueous humor production
CAIs and acid/base concs in body?
- H2CO3 (carbonic acid) which is a weak acid, is retained
- Urine contains less H+
- Blood contains more acid
CAIs ___ the pH of the urine
increase (more alkaline)
Indications of CAIs
*Glaucoma (main), urinary acidosis, metabolic alkalosis, acute mtn sickness, inc IOP post op cataract surgery, aspirin overdose
Absorption of CAIs?
absorbs well (oral and ocular)
Why are CAIs given in aspirin overdose?
aspirin is a weak acid and therefore will be excreted more quickly in alkaline urine
CAIs: onset, duration, peak
30 min, 12 hr, 2 hr
CAIs work on the… (part of nephron)
PCT
CAI ADRs
*drowsiness (MC), renal stones, K wasting, hypersensitivity rxn
CAI CIs
hepatic cirrhosis
Which dosage form of CAIs decreases systemic absorption, decreasing side effects?
ocular/topical (dorzolamide, brinzolamide)
What technique can be done to decrease systemic absorption of CAIs?
nasolacrimal duct block
How do you do the nasolacrimal duct block?
put drops in, close eyes, apply pressure to nasolacrimal ducts for 1-2 mins
-not guaranteed to completely prevent systemic absorption
Are CAIs usu used single or in combo?
BOTH! (combo w/ b-blockers)
What is H2CO3s conjugate base?
HCO3- (bicarbonate ion)
H2CO3 is a… (acid or base)
weak acid
Adenosine antagonists work on which parts of the nephron?
PCT, collecting tubule
Adenosine affects which parts of the nephron?
glomerulus, PCT, asc limb of LOH, collecting duct
Adenosine antagonists work how?
diuretic effects, work on coll tubule and PCT, work like caffeine
Name the Loop diuretics (4)
furosemide, torsemide, bumetanide, ethacrynic acid
MC loop used?
furosemide
MOA of loop diuretics?
Inhibits Na 2Cl K transporter;inhibits their active transport Stop ions (Na, K, Cl) from being reabsorbed, more are excreted into the urine along with H2O
Loops work on what part of nephron?
thick ascending limb of LOH
Indications of Loops?
- *Edema (MC, very effective)- CHF
- HTN (less used for this)
- Hypercalcemia, hyperkalemia (gets rid of excess ions in the plasma)
- Anion overdose (fluoride, bromide, iodide)
T or F, Loops are a high ceiling effect med?
True. (ceiling effect- near max diuretic effect; if you go over max, won’t be beneficial)
Loops in combo with what have bet combined effect/highest amount of Na blocking over time?
thiazides
Loops absorption
orally well absorbed
Loops available in these routes of administration:
oral, IV
What are the best drugs to diurese pts?
loops
Torsemide vs furosemide onset and duration?
T: o- 1 hr, d- 4-6 hrs (short onset, long duration)
F: o- 2-3 hrs, d: 2-3 hrs (longer onset, shorter duration)
Loops ADRs
- hypo- mg, ca, k, na, cl
- hyperuricemia
- ototoxicity (if given w/ other ototoxic meds)
- allergic rxn
- increase Scr
Loops CIs
- overuse in hepatic cirrhosis, renal failure (nephrotoxic, heart failure
- sulfa allergies
best loop to give in sulfa allergic pt?
ethacrynic acid (no sulfa group)
Loop diuretic drug-drug interactions
NSAIDs- will decrease effectiveness of loops. Don’t stop NSAIDs, just find a balance
Furosemide PO:IV conversion
2:1 (ex 40 mg PO= 20 mg IV)
Torsemide PO:IV conversion
1:1
Bumetanide PO:IV conversion
1:1
Conversion btw loops (F:T:B)
40 mg furosemide= 20 mg torsemide= 1 mg bumetanide
most potent loop?
bumetanide
Are diff loops interchangeable?
yes, can switch from one to another at any time
List the thiazide diuretics
HCTZ, chlorothiazide
List the thiazide-like diuretics
metolazone, indapamide, chlorthalidone
Which drug class has a ceiling effect?
loop diuretics
MOA of thiazides?
Inhibit NaCl transporter, enhance Ca reabsorption; NaCl and water are excreted
Which part of nephron do thiazides work?
DCT
Thiazides indications
*HTN (MC), heart failure, nephrogenic DI, nephrolithiasis
Thiazides absorption
Slowly
Which thizide or thiazide like diuretic absorbs the slowest but has the longest duration of action?
chlorthalidone (thiazide-like)
MC used thiazide in practice?
HCTZ
Thiazides are weak or strong diuretics?
weak
Thiazides ADRs
- hypo- Na, Cl, K,
- hyper- uric acid, Ca, glucose, lipids
- allergic rxn (sulfa)
- photosensitivity
- orthostatic hypotension (minimal)
Thiazides CIs
-Overuse in: hep cirrhosis, renal failure, CHF (dont give high doses)
Thiazides caution in pts with which allergy?
sulfa
Thiazides may be ineffective in these pts
pts w/ CrCl less than 20 ml/min, EXCEPT metolazone (thiazide like)
Only thiazide that is effective in pts w/ low CrCl?
metolazone (thiazide-like)
Which thiazide diuretic is the only one that is available in IV form?
chlorothiazide (thiazide)
What routes of admin are thiazides available in?
oral (most) and IV (chlorthiazide)
What drug class are not structurally like thiazides, but contain a sulfonamide group and have the same MOA as thiazides?
thiazide-like diuretics
List the K- sparing (aldosterone receptor blocker) diuretics
Spironolactone, eplerenone
List the other K- sparing agents
Triamterene, amiloride
K- sparing (aldosterone receptor blocker) diuretics MOA
block aldosterone receptors (antagonize mineralcorticoid receptors) in the collecting tubules, preventing aldosterone from binding; More K and H stays in plasma
Where in the nephron do K- sparing (aldosterone receptor blocker) diuretics work?
cortical collecting tubule
Indications for K- sparing (aldosterone receptor blocker) diuretics
- hypokalemia prevention and tx
- Spironolactone: hyperaldosteronism, PCOS, hirsutism
T or F? Spironolactone has a slow onset, duration, and peak?
True
Does spironolactone take a while to reach therapeutic levels?
Yes- several days
K sparing diuretics ADRs (all types)
hyperkalemia
Spironolactone ADRs
gynecomastia, impotence, tumorogenic (animals)
K sparing diuretics CIs (all types)
hyperkalemia, renal impairment, hepatic impairment
Spironolactone CIs
Addison’s dz
Eplerenone drug-drug interactions
-strong CYP3A4 agents- grapefruit, fluconazole, diltiazem (EPLERENONE ONLY)
K sparing diuretics (other) MOA
inhibits JUST the Na ion channels in the collecting tubules
Triamterene onset and duration
o- 2-3 hrs
d- 7-9 hrs
Triamterene ADRs
kidney stones
Which is more effective, triamterene or spironolactone?
spiro
List the INDIRECT ADH antagonists
Lithium, demeclocycline
List the DIRECT ADH antagonists
conivaptan, tolvaptan
T or F? Li and Na are the same size
T
INDIRECT ADH antagonists MOA?
unknown; DO NOT work on ADH receptors
DIRECT ADH antagonists MOA?
inhibit vasopressin (ADH) receptors; ADH blocked and H2) is not retained
ADH antagonists work on which part of the nephron?
collecting duct
Are ADH antagonists used often?
No
ADH antagonists (direct and indirect) indications
CHF, SIADH
Direct ADH antagonists onset/peak/duration?
o- 2-4 hrs
p- 4-8 hrs
d- 24 hrs
How often are direct ADH antagonists taken per day?
1x/day (bc they last 24 hrs)
Direct ADH antagonists ADRs?
Nausea, dry mouth, thirst
Direct ADH antagonists CIs?
hypovolemia, hyponatremia
Direct ADH antagonists drug-drug interactions?
-strong CYP3A4 agents- grapefruit juice, fluconazole, diltiazem
List the osmotic diuretics
Glycerol, mannitol
Mannitol available forms?
PO, inhalation, IV
Osmotic diuretics MOA?
increase osmotic pressure in the glomerulus, decreasing water and electrolyte reabsorption
Osmotic diuretics indications?
- cerebral edema (head injury)
- acute glaucoma
- bronchial hyperresponsiveness
Describe the absorption, excretion, duration of osmotic diuretics?
poorly absorbed, quickly excreted, don’t last long
Osmotic diuretics ADRs?
- Glycerol (oral form)- N/V/Diarrhea
- Mannitol- excess volume expansion, can cause HF, edema, pulm congestion (pulling water out of bloodstream into the tissues)
Osmotic diuretics CIs
hypersensitivity
How should you take oral osmotic diuretics?
mix w/ small amount of juice (OJ preferred), add ice, sip SLOWLY, small sips
How should IV mannitol be infused?
SLOWLY
Mannitol IV is indicated for what pt population?
inpts, esp head injury, edema
Sulfonamide chemical structure?
SO2NH2
How many chemical arrangements of sulfonamides are there?
3
Can pts w/ sulfa abx allergy receive loop diuretics?
yes. caution. best=ethacrynic acid
No cross sensitivity for sulfonamide allergic pts taking loops:
abx, other sulfonamide containing meds
3 questions to ask pt when they say they have a med allergy?
- what allergies?
- what happens?
- how long ago?
Definition: Volume of plasma filtered across the glomerulus per unit of time
glomerular filtration rate (GFR)
MC method for measuring kidney fn?
GFR
The GFR reflects the number of..
functioning nephrons in the kidney
GFR normal range
90-120 ml/min
T or F? GFR is easy to measure directly
F
Definition: endogenous byproduct of musc metabolism
serum creatinine
how much of Cr is cleared by the kidneys? (%)
100%
__% of Cr is cleared by glomerular filtration, and __% through tubular secretion
90%, 10%
Scr is ____ (lower/higher) in elderly and paraplegics?
lower (less musc tone/mass)
How do you DIRECTLY measure renal fn/creat?
24 hr urine collection
How do you INDIRECTLY measure renal fn/creat?
calculation based on SCr
Definition: rate at which the kidneys clear Cr from the blood
CrCl
Name of the formula used to calculate CrCl
cockroft-gault formula
when calculating crcl on females, what do you have to add to your calc?
multiply by 0.85
If pts body weight is less than IBW, use the ___
actual body weight
If pts body weight is 20% more than IBW, use the ____
adjusted body weight
If pts weight is more than IBW, but less than 20% above it, use the ____
ideal body weight
AKI clinical presentation
-inc Scr, dec GFR, accumulation of nitrogenous wastes, inability to regulate fluids/electrolytes/acid base balance, weight gain (edema), foamy urine, changes in urinary habits
3 categories of AKI
Prerenal, intrinsic, postrenal (also functional?)
AKI from hemodynamic changes without hypotension or structural damage
functional
Decrease in renal perfusion
prerenal azotemia
Structural damage inside the kidney
intrinsic
obstruction of urine flow
postrenal
Prerenal: urine sediment
normal
Prerenal: urine RBCs
none
Prerenal: urine WBCs
none
Prerenal: urine Na
Less than 20
Prerenal: urine/serum osmolarity
> 1.5 (highest of the 3)
Prerenal: urine/scr
> 40:1 (highest)
Prerenal: BUN/Scr
> 20 (highest)
Intrinsic: urine sediment
casts, cellular debris
Intrinsic: urine RBCs
2-4+ (most)
Intrinsic: urine WBCs
2-4+ (most)
Intrinsic: urine Na
> 40
Intrinsic: urine/serum osmo
Less than 1.3
Intrinsic: urine/Scr
Less than 20:1
Intrinsic: BUN/Scr
15
Postrenal: urine sediment
cellular debris
Postrenal: urine RBCs
variable
Postrenal: urine WBCs
1+ (middle)
Postrenal: urine Na
> 40
Postrenal: urine/serum osmo
Less than 1.5
Postrenal: urine/Scr
Less than 20:1
Postrenal: BUN/Scr
15
Name the type of AKI caused by: hypovolemia
prerenal
Name the type of AKI caused by: obstruction (upper-kidney, lower-bladder, prostate, catheter)
postrenal
Name the type of AKI caused by: decreased cardiac output
prerenal
Name the type of AKI caused by: radiocontrast dyes, APAP, cisplatin
intrinsic (acute tubular necrosis)
Name the type of AKI caused by: rhabdomyolysis
intrinsic (acute tubular necrosis)
Name the type of AKI caused by: decreased blood volume
prerenal
Name the type of AKI caused by: infection
intrinsic
Name the type of AKI caused by: ACE-I, NSAIDS
prerenal (impair renal perfusion)
Name the type of AKI caused by: PCN, cephalosporins, sulfonamides, rifampin, phenytoin, furosemide, PPIs, NSAIDs
intrinsic (nephritis)
How many stages of AKI/ARF are there?
3
How are the stages classified (what are they based on?)
Scr and urine output
Normal Scr value (men)
0.7-1.3 mg/dL
Normal Scr value (women)
0.6-1.1 mg/dL
What is used as the reference Scr?
lowest Scr recorded in the last 3 months
What are the 3 urine output classifications?
non-oliguria (normal), oliguria, anuria
non-oliguria numbers
adults >400 ml/day or >.5 ml/kg/hr
peds >1ml/kg/hr
peds UO classified based on___
weight
oliguria #s (adults)
A-less than 400 ml/ day or less than 0.5 ml/kg/hr for >6hrs
Anuria #s (BOTH adults and peds)
Less than 50 mls/day
Medication induced AKI: Which meds change renal hemodynamics by vasoconstricting the afferent arteriole?
NSAIDs, cyclosporine, tacrolimus, amphotericin B, radiocontrast agents, vasopressores
Medication induced AKI: Which meds change renal hemodynamics by vasodilating the efferent arteriole?
ACEIs, ARBs, diltiazem, verapamil
Medication induced AKI: Which meds cause direct toxicity to the renal tubules?
aminoglycosides, amphotericin B, radiocontrast agents, cisplatin/carboplatin (platinum chemotherapy agents)
5 things that place pt at higher risk for AKI
- hx CKD
- increased age
- comorbid conditions (DM)
- dehydration
- pt on AKI inducing medication
Most important way to prevent AKI, esp when giving direct tubular toxic agents
adequate hydration, dilute toxic agents
What steps do you need to take before giving a pt a radiocontrast agent?
- administer oral or IV hydration for 6-12 hrs prior
- Give NAC (N-acetylcysteine)- 4 doses PO
- Use low or iso-osmolar agent
Steps for tx of AKI (4)
- Evaluate pt fluid status (hyper or hypovolemic)
- ID cause of AKI (meds?)
- Review meds for renal dose adjustments
- Supportive therapy
If AKI pt is hypervolemic, how would you tx?
diuretic or renal replacement therapy (dialysis)
If AKI pt is hypovolemic, how would you tx?
fluids (crystalloid, colloid)
If cause of AKI is medication elated, what do you do?
- stop offending med
- start steroids (prednisone or methylprednisolone)
What is included in supportive therapy for AKI pts?
- dialysis
- adequate hydration
T or F, there is a drug that has been proven to accelerate the recovery of renal failure
F- NONE; protection/prevention is key