C: Diuretic Drugs

Front 1

What are the segments of the renal tubules from filtration --> collection?

Which are water permeable?
Impermeable, and what is this section called? What *is* absorbed in this section?

What does this reabsorption produce?

What happens in the CT w/ ADH? w/o ADH?

Back 1

proximal tubule -> descending thin limb (DTL) -> Ascending thin limb (ATL) -> Thick ascending limb (TAL) -> Distal Tubule (Dt) --> collecting duct (CT)

PT, DTL, and CT (inlcluding late DT)
ATL, TAL, DT = diluting region
Na+

"Free water", i.e., hypoosmotic TF (tubular fluid)

most of the "free water" is reabsorbed --> concentrated urine
no/little reabsorption -> dilute urine.

Front 2

___% of filtered salt load is reabsorbed under normal conditions? % filtered plasma (tubular fluid)?

Does normal creatinine = normal renal function?

Kidneys make up 0.5% of body weight, yet consume 7% of total body O2. Why?

What is the driving force behind reabsorption of water?

Back 2

>99%; >99%

No; there is *significant* renal reserve.

Most is from ATP production which drives the Na+ reabsorption pump.

Na+ reabsorption.

Front 3

There are 7 types of Na+ transport in the renal tubules. __ are active on the lumen/cell border, while ___ is active on the cell/blood border. ___ is on the junction.

Which is the only one driven by ATP? Why is it so important?

Back 3

5, 1, 1.

the cell/blood Na+/K+ exchanger ATP-ase. It maintains the low [Na+] in the cell, which is what drives the luminal symports/antiports/etc.

Front 4

__% of the filtered load Na+ is reabsorped in the PT. DTL? TAL? What type of transporter, primarily, in the TAL?

What other ions are significantly reabsorbed in the TAL?

Is there significant Na+ reabs in the DT? Ca++? How so?

Back 4

~55%; 0% (impermeable), 25-40%

Na, 2Cl, K cotransporter

Mg++, and Ca++ (a little K+ too)

Yes, 5-10% via Na,Cl cotrans.
Yes, dependent on PTH.

Front 5

What modifies the Na reabs in the CT?

Back 5

+ by ALD, - by ANP

Front 6

What are the 5 classes of Diuretic agents?

Back 6

Osmotic
Carbonic anhydrase inhib (CAI)
Loop (Na, K, Cl trans)
Thiazide (Na, Cl trans)
K+-sparing: two subtypes:
- Nachannel blockers
- mineralocorticoid receptor (MR) antag.

Front 7

Mannitol, urea
- class
- mechanism
- site of action
- uses?
- toxicities?
- contraindications?

Back 7

osmotic diuretic
- expand the ECFV via osmolarity shift... they are freely filtered (and neither reabs nor secreted)... so they draw more water *into* the tubule in the H20 perm. segs.
... effect Na reabs in all segs.
**do not directly affect the tubules**
- entire renal tubule
- CSF vol reduction; prophylaxis and early tx of acute renal fail (ARF) from severe trauma/surg; glaucoma (short term)
- headache, nausea, vomiting, rebound cerebral edema, renal fail
- CHF and pulm edema

Front 8

What are the 6 general uses of diuretics?

Back 8

edematous states
maintainence of urin flow
HTN
diabetes insepidus
Nephrolithiasis (stones)
Hypercalcemia

Front 9

Acetazolamide
- class?
- mech?
- acidic/alkaline urine? what ions are secreted? **hallmark**?
- uses?
- side effects?

Back 9

- CAI
- block HCO3- reabs via CA inhibition --> mild to moderate diuretic effect
- alkaline; HCO3-, K+, and Na+, ***no Cl- uretic effect***
- limited, most common is glaucoma; also acute altitude sickness and metabolic alkalosis.
- Metabolic acidosis, Renal stone formation, K+ wasting, sulfonamine hypersensitivity/photosensitivity rxns

Front 10

How is Carbonic Anhydrase involved in HCO3- reabs? Explain the generalities of this cycle.

What keeps the thing moving in the right direction?

Back 10

The Na/H antiport gives the lumen a proton (H+). This b/ HCO3- --> H2CO3 --<CA>--> H20 + CO2

The CO2 diffuses freely back into the cell --<CA>--> H2CO3 --> HCO3- --> out of the cell via the 3Na+ HCO3- cotransporter.

(1) stready production of the HCO3- inside the cell b/c the sodium/H+ antiport is taking away the H+.
(2) the 3Na/HCO3- cotrans is taking that ion out of the cell.

Front 11

How can CAI cause K+ wasting?

Why do TAL cells have especially high concentrations of K+?

Back 11

increased load of Na is presented to the late distal segments of the tubule. (same as the mech of thiazide diuretics)

They have the Na, 2Cl, K pump as well as the Na/K AtPase.

Front 12

Fourosemide, Bumetanide, Torsemide
- class? aka?
- Na excre %?
- how get into tubule?
- inhibitor of diuretic response?
- mech?
- mech of K+ wasting?
- uses?
- toxicities?

Back 12

- loop diuretics (affect the TAL) = "high ceiling diuretics" = most potent class!
- 25-40%
- organic secretion in the PT (they're b/ plasma protein)
- probenecid
- inhib Na, K, 2Cl transporter in TAL --> kidney can't concentrate urine.
- it doesn't get picked up by the cotransporter
- CHF, ARF, edema of cardiac, renal, or hepatic origin. Can be used to treat hypercalcemia, but must replace salt in those pts.
- serious depletion of Na, drop in ECFV --> circ collapse & thromboembolic episodes
... cardiac arrhythmias from K drop
...metabolic alkalosis due to H+ excretion
...Ototoxicity (deafness, tinnitus) b/c this cotransporter is also in the ear
...hyperuricemia
...hyperglycemia->diabetes mell
...sulf hyper/photosens.

Front 13

Ethacrinic Acid
- class?
- differences?

Back 13

loop diuretic

non sulf toxicity, but increased ototoxicity.

Front 14

In which class of diuretics can massive intravascular volume depletion also activate the RAS leading to Aldosterone induced K+ excretion?

Back 14

Loop.

Front 15

Difference in excreted urine concentrations b/t Thiazides and CAIs?

Back 15

Thiazides cause Cl- excretion, and less HCO3- excretion.

Front 16

HCT, Metaolazone
- location of action?
- mech?
- inhibitor?
- why isn't diuretic effect larger?
- effect on Ca++?
- uses?
- have a paradoxical effect i/ what pts?
- toxicities?

Back 16

- luminal membrane of early DT
- inhibit electroneutral Na/Cl cotrans in the DT.
- probenecid
- most Na has already been reabs by the time it reaches the site of HCT action.
- increase PTH-regulated reabs
- **agent of choice in CHF**, also used in HTN, also renal stones b/c of Ca effect.
- 50% decrease in urine V in diabetes insipidus.
- K+ wasting, metabolic alkalosis (^H+ excre), gout, impair pancreatic release of I, sulf/photo

Front 17

Spironolactone
- class/subclass?
- mech?
- requirement?
- reversal?
- uses?
- toxicitities?
- efficacy might be reduced by?

Back 17

- K+ sparing, aldosterone antag
- b/ competitively to MR in cytoplasm in late DT and CT --> blocks reabs of Na into interstitum, and thus no gradient exists for K secre.
- only effection in presence of aldosterone
- increase aldosterone lvls
- coadmin w/ HCT and loop to tx edema & HTN --> less K wasting
...tx primary aldosteronism
...tx edema of 2nd. aldosteronism.
- life threatening hyperkalemia. other steroid-associated side-effects too.
- salicylates or other things competing for PT secretion.

Front 18

Eplerenone
- class/subclass?
- mech?
- requirement?
- reversal?
- uses?
- toxicitities?
- efficacy might be reduced by?

Back 18

- K+ sparing, aldosterone antag
- b/ competitively to MR in cytoplasm in late DT and CT --> blocks reabs of Na into interstitum, and thus no gradient exists for K secre.
- only effection in presence of aldosterone
- increase aldosterone lvls
- Ht fail post MI and in HTN
- life threatening hyperkalemia. other steroid-associated side-effects too.
- salicylates or other things competing for PT secretion.

Front 19

Amiloride, triamterene
- class/subclass?
- extent of Na excre effect?
- mech?
- depend on aldosterone?
- uses?
- toxicity?

Back 19

- K sparing diuretics, selective Na+ channel blockers
- moderate b/c acts in late DT/CT
- block electrogenic Na channels in late DT and CT
- no
- combo w/ HCT/loop = stop K wasting; used to treat CF (aerosol).
- life threatening hyperkalemia; nausea, vomiting, leg cramps, etc.

Front 20

quinidine-like antiarrhythmics + diuretics = bad shit. why?

digitalis + thiazide & loop = ?

Back 20

can kill pt by diuretic causing hypokalemia --> raises risk of torsades de points --> fatal v.fib.

arrhythmias.

Front 21

NSAIDs ____ diuretic response. Less so in pts with what?

NSAIDS may ____ hyperkalemia caused by the K sparing agents.

If the ECFV is depleted too much by diruetics, what will that do to the [drugs] in the system?
ex. do what to ASA?

Back 21

attenuate.

**reduces action of diuretics in those w/ CHF, hepatic cirrhosis w/ {ascities, chronic renal dz, or hypovolemia}.

potentiate

increase their concentrations... increase their side effects.
- can increase ASA toxicity

Front 22

Class the following drugs:
mannitol
eplerenone
acetazolamide
furosemide
spironolactone
triamterene
amiloride
toresimide
bumetanide
HCT
metolazone
urea

Back 22

Osmotic diuretics: mannitol, urea;
Carbonic anhydrase inhibitors: acetazolamide;
Loop diuretics: furosemide, bumetanide, torsemide;
Thiazides: hydrochlorothiazide, metolazone;
Potassium-sparing diuretics: amiloride, triamterene, spironolactone, eplerenone.