PostMT Diuretics

Question 1

What is reacsorbed in PCT?

Answer 1

65% of Na, K, water
85% NaHCO3
100% of glucose and amino acids

Question 2

What is reabsorbed in thick ascending LoH?

Answer 2

Impermeable to water.

25% of filtered Na reabsorbed

Question 3

What establishes the cortex and medulla concentration gradient?

Answer 3

The Na/K/2Cl cotransporter in the thick ascending limb.

Question 4

What drives Mg and Ca paracellular reabsorption?

Answer 4

The diffusion of K back into the lumen due to the incrased intracellular concentration gradient that creates an ELECTROPOSITIVE status in the lumen.

Question 5

What % of Na is reabsorbed in DCT?

Answer 5

10%

Question 6

What is Ca reabsorption regulated by in the DCT?

Answer 6

PTH

Question 7

What is Ca reabsorption regulated by in the thick ascending limb?

Answer 7

electropositive gradient produced by K

Question 8

Where does K balance and seretion primarily occur?

Answer 8

CCT

Question 9

What are Aldosterone’s action?

Physiological results?

Answer 9

Na reabsorption
H+ expelled
K+ expelled
Results in increased water retention&raquo_space; increased blood volume&raquo_space; increased BP

Question 10

What regulates ADH levels?

What does alcohol do?

Answer 10

serum osmolarity and volume

Alcohol decreases ADH release and increases urine production.

Question 11

What two drug classes decrease body pH?

Answer 11

CAi’s (decrease bicarb formation in cytosol of PCT cells = decrased bicarb into interstitum&raquo_space; less to body)
K-sparing (block Na channels, so Na cannot leave lumen = lumen remains more electropositive)

Question 12

What two diuretic classes increase NaCl urinary content the most?

Answer 12

Loops and even greater, Loops + thiazides
Loops = block Na/K/2Cl
Thiazides = block Na/Ca cotransporter

Question 13

What diuretic class increases urinary NaHCO3 most?
What has no effect on NaHCO3 urinary levels?

Answer 13

CAi’s

Loops

Question 14

What increases urinary K most?

Answer 14

Loops + thiazides

Question 15

CAi

Answer 15

acetazolamide

Question 16

CAi location of action and MOA

Answer 16

PCT

abolition of NaHCO3 reabsorption

Question 17

Urinary and body result of CAi

Answer 17

DECREASED body pH (due to less bicarb reabsorbed).
INCREASED urinary pH (due to more NaHCO3).
Bicarb-esis, natriuresis, diuresis

Question 18

How fast to CAi’s work?

Efficacy short or long course of admin?

Answer 18

Apparent within 30 min.

Significant loss of efficacy after several days of use.

Question 19

CAi toxicity

Answer 19

• Metabolic acidosis.
• Ca2+ stones due to pH alkalinization (decreased calcium salt solubility)
  Paresthesia, sulfonamide hypersensitivity

Question 20

Cirrhosis is a contraindication for use of what diuretic? Why?

Answer 20

CAi use.

1. alkalinization of urine results in hyperammonemia and hepatic encephalipathy

Question 21

What three things are contraindications of CAi’s?

Answer 21

Cirrhosis, severe COPD, hyperchloremic acidosis

Question 22

Clinical indications of CAi’s?

What’s it rarely used for?

Answer 22

glaucoma,
urinary alkalinization or metabolic alkalosis
ACUTE MOUNTAIN SICKNESS

Rarely used as antiHTN.

Question 23

Loop Diuretics
Names
Best used for what?

Answer 23

furosemide and ethacrynic acid

Most efficacious diuretic/volume depletion class.

Question 24

Metabolism of CAi’s

Answer 24

excreted unchanged - no hepatic metabolism

Question 25

Loop half life is correlated with what? Why?

Answer 25

Correlated with kidney function because it works on luminal side of tubule at Na/K/2Cl cotransport.

Question 26

Co-administration of NSAIDS with a Loop (esp in a person with cirrhosis or nephritic syndrome) could result in what?

Answer 26

Reduction of loop secretion due to competition for weak acid secretion. NSAIDs interfere because they reduce PG synthesis.

Question 27

What do Loops cause?

Answer 27

uresis of Mg, Ca, Na, K, and water Synthesis of PGs Increasein renal blood flow to vascular beds Weak inhibitors of CAi's

Question 28

Loop toxicity

Answer 28

hyponatremia (hepatic enceph in liver diseased patients) hypokalemia, Mg, uricemia ototoxicity (associated with renal dysfunction) hyperuricemia

Question 29

Contraindications of Loops

Answer 29

furosemide, bumetanide, torsemide may cause sulfa allergic reactions HEPATIC CIRRHOSIS, HF, or renal failure post-menopausal osteopenic women

Question 30

Clinical indications of Loops

Answer 30

pulm edema, HTN, HF, hyperK Anion overdose - coadmin loop and saline hypercalceimic states

Question 31

Thiazide diuretic

Answer 31

hydrochlorothiazide

Question 32

Half life of HCTZ | MOA

Answer 32

47 hours | block Na/Cl in DCT

Question 33

HCTZ toxicity

Answer 33

``` hypokalemic metabolic alkalosis and hyperuricemia *HYPERGLYCEMIA and UNMASK DIABETES *HYPERLIPIDEMIA hypoNa, hyperCa, hyperUrecemia Sulfonamide hypersensitivity ```

Question 34

HCTZ contraindications

Answer 34

Will decrease effectiveness of anticoags for gout, insulin, loops *DIABETIC PATIENTS NSAIDs and COX-2 inhibitors Hepatic cirrhosis, renal failure, HF

Question 35

Clinical indications of HCTZ

Answer 35

HTN, HF Nephrolithiasis due to hypercalcinuria NEPHROGENIC DI

Question 36

K Sparing Diuretics

Answer 36

Mineralicorticoid receptor (MR) antagonist prototype - SPIRONOLACTONE >> eplerenone (analog) Na channel inhibitor prototype: AMILORIDE and triamterene

Question 37

Eplerenone inactivation location

Answer 37

liver

Question 38

What is a spironolactone analog with greater MR selectivity?

Answer 38

eplerenone

Question 39

What Na-channel inhibitor do you give if you want less frequent dosing?

Answer 39

amiloride

Question 40

MOA of MR antagonists

Answer 40

They are synthetic steroids that are competitive inhibitors of aldosterone binding to the MR (a nuclear hormone).

Question 41

What is MR?

Answer 41

A nuclear hormone

Question 42

What is unique about MR antagonists?

Answer 42

Only diuretic that does not require access to tubular lumen to induce diuresis. *Reduce mortality in HF!!

Question 43

MOA of amiloride and triamterene

Answer 43

directly inhibit Na entry to DCT principle cells though Na channels

Question 44

Toxicity of K-sparindg diuretics

Answer 44

extreme hyperK - esp use of renin-reducing agents like B-blockers met acidosis BPH, impotence

Question 45

Stones can be caused especially by what K-sparing diuretic?

Answer 45

triamterene

Question 46

Contraindications of K-sparine

Answer 46

chronic renal insuff | B-blockers, NSAIDS, ACEis, ARBs

Question 47

Clinical inidcations of K-sparing?

Answer 47

hyperaldosteronism or MC excess | thiasizeds and loops

Question 48

What are osmotic agents that alter water excretion? Administration route? Metabolized?

Answer 48

Mannitol given parenterally Not metab. Excreted within 30-60min

Question 49

MOA of mannitol REsutls in what?

Answer 49

increase osmotic pressure of glom filtrate >> inhibit tubular reabsorption of wtaer >> decrease urine REsults in Natriuresis and diuresis

Question 50

Mannitol opposes what effects in CCT?

Answer 50

ADH

Question 51

Mannitol toxicity

Answer 51

EC volume expansion and hyponatriemai

Question 52

Contrainidications of mannitol

Answer 52

dehyrdation, hyperK, hyperNa

Question 53

Mannitol clinical indications

Answer 53

increase urine volume | REDUCE ICP OR INTRAOCULAR PRESSURE

Question 54

What are effects of ADH agonists that alter water excretion?

Answer 54

Increased water reabs in CCT

Question 55

ADH agonist are treatment of choice in what disease?

Answer 55

Pituitary DI

Question 56

What is a ADH antagonist that alters water excretion? What do you use it to avoid?

Answer 56

Conivaptan | Use because you want to avoid hyponatremia caused by ADH excess

Question 57

Conivaptan admin route

Answer 57

parenterally

Question 58

Toxicity of Conivaptan

Answer 58

hyperNa | nephrogenic DI

Question 59

When do you use Loops and thiazides?

Answer 59

When you want to block Na reabsorption from all three segments. Loops - block in thick ascending limb Thiazides - block in DCT and cause mild natriuresis in PCT

Question 60

Adverse effect of loops and thiazides

Answer 60

K-wasting

Question 61

What edematous states are treated with diuretics?

Answer 61

HF Kidney disease/renal failure Hepatic cirrhosis

Question 62

What nonedematous states are treated with diuretics?

Answer 62

HTN Nephrolithiasis HyperCa DI

Question 63

Why does HF cause an edematous state?

Answer 63

Decreased CO >> decreased BP sensed leads to retention of Na and water >> unecessary retention of water >> pulm or interstital edema result

Question 64

Why does kidney disease cause an edematous state?

Answer 64

Renal disease = retention of salt and water, sometimes K = diruetics useful

Question 65

When should diuretics be used in hepatic cirrhosis-caused edema?

Answer 65

Useful for when edema and ascites become severe due to liver disease. DO NOT USE aggressively in patients wtih liver disease....

Question 66

What diuretics are used in HTN (nonedematous state)?

Answer 66

Thiazides or loops, combo with vasodilator (bc cause signif salt and water rentention)

Question 67

What diuretics are used in nephrolithiasis (nonedematous state)?

Answer 67

Thaizide to reduce urinary Ca concentration and enhance Ca reabsorption

Question 68

What diuretics are used in hypercalcemia (nonedematous state)?

Answer 68

Loops coadmin with saline to maintain effective Ca diuresis without volume contraction.

Question 69

What diuretics are used in DI (nonedematous state)?

Answer 69

Supplementary ADH only useful when it's central DI. Thiazides reduce polyuria and polydypsia in both nephrogenic DI (inadequate responsiveness to ADH) and neurogenic/central DI (deficient ADH production)

Question 70

Membrane transport protein diuretics

Answer 70

lops thiazides K-sparing

Question 71

Enzyme diuretics

Answer 71

CA

Question 72

Hormone receptor diuretics

Answer 72

MR (K-sparing)