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Flashcards in Diuretics - Bahouth Deck (77)
1

What is the main idea of diuretics?

To mobilize sodium, leading to urination

2

What is Aquaporin-1 found? Aquaporin-2

In the PCT and the descending loop of henle

In the CD

3

What makes the interstitium hyperosmotic and how does this affect the collecting duct?

The TALH makes the interstitium hyperosmotic by secreting Na. This makes the CD want to reabsorb water.

4

What percent of Carbonic Anyhydrase is found in the PCT and what percent in the DCT?

90% and 10%

5

What is the mechanism of action of Carbonic Anhydrase Inhibitors?

Inhibit CA, resulting in HCO3 loss in the urine

6

What is the net effect of CAinh?

Alkaline urine, due to Na-Bicarb loss in the urine. Systemic acidosis because of the HCO3 loss. Enhance Cl reabsorption resulting in acidosis.

7

What are the clinical uses of CAinh?

Diuretics: limited use (1-2 days)
Alkalinize urine
Reduce intraocular pressure (in glaucoma surgery)
Management of seizues (unk)
Given prophylactically for mtn sickness

8

What is the only diuretic we need to know?

Acetazolamide (oral 500 mig BID)

9

What are the side effects of CAinh?

Metabolic Acidosis
Markedly increases K loss in the urine

10

Explain the normal pathway of HCO3 and H due to CA?

HC03 and H are in the lumen urine, where they combine to form H2C03. CA then acts to convert the acid to water and carbon dioxide, which can freely cross the membrane and reenter the cell. Once in the cell, CA turns C02 and H20 into carbonic acid again. This then turns to H and HC03, with the H excreted to bring in Na. The secreted H then goes to bind with bicarb in the urine.

11

What are the minor effects of osmotic diuretics? Where is this happening?

In the PCT, osmotically inh Na and H20 reabsorption

12

What are the characteristics of osmotic diuretics?

Small molecules that are filtered but not reabsorbed by the kidney

13

What is the major use of osmotic diuretics and where does this occur?

LOH

They increase osmolarity of plasma
Extract water from peripheral tissues and decrease blood viscosiy
increase medullary renal blood flow and reduce its tonicity
impair water reabsorption by thin descending loop of henle
impair nacl and urea extraction by thin ascending loop of henle
interfere with transport processes in the TALH

14

How do osmotic diuretics work?

They impair water reabsorption in the descending loop of henle and na reabsorption in the TALH. This increases the amount of h20 in the tubular system

15

What are the clinical uses of osmotic diuretics?

tx of dialysis disequilibrium syndrome
reduce intracranial pressure
reduce intraocular pressur

16

what is an example of osmotic diuretics?

mannitol

17

what are the side effects of osmotic diuretics?

volume overload (what does this mean...? how?)
contraindicated in cardiac failure

18

What are the mechanisms of loop diuretics?

inhibit NaK2Cl symporter in TALH
inhibit the ability of the macula densa to sense NaCl
Stimulate biosynthesis of prostaglandins
increase total renal blood flow
maintain gfr
POTENTLY INCREASE RENIN RELEASE BY:
inh macula densa
reflexely activating the sympathetic NS
stimulating intrarenal baroreceptor mechanisms

19

What does the Macula Densa want to normally do? Why is it important that the loop diuretics inh the macula densa?

MD wants to shut afferent arteriole so that they can reabsorb more Na. So these drugs prevent MD from sensing NaCl, so it cannot close afferent arteriole. This leads to more urine.

20

What percentage of Na is reabsorbed in the TALH by the NaK2Cl?

25%

21

Why do we give loop diuretics

They give the maximum amount of response for a drug

22

What are the net effects of loop diuretics?

Most potent class of diuretics in mobilizing NaCl
Copious diuresis and significant NaCl loss
Increase urinary excretion of K/H
Increase excretion of Ca and Mg
Impair the ability of the kidney to concentrate urine

23

Of the three ions involved in the NaK2Cl , which is the driving force? Which is the one that is filtering into and out of the cell?

Na is the driving force (Na is being pumped into interstitium, lowering the cellular concentration so sodium wants to freely come through

K is cycling into and out of the cell and lumen

24

What are the therapeutic uses of loop diuretics?

Edema of cardiac, hepatic or renal origin (GFR <30)
Pulmonary Edema
Hypercalcemia to mobilize Ca
Protect against renal failure
Washout of toxins by increasing urine flow
Antihypertensive diuretics used with other drugs

25

What are the examples of loop diuretics?

Furosemide, Bumetanide, Torsemide,

26

What is important about the administration of furosemide?

Has to be taken in and then SECRETED, to affect the NaK2Cl transporter from inside the lumen

27

What are the pharmacological effects of furosemide?

Copious diuresis with significant NaCl losses
Increased urinary excretion of K/H
Urinary excretion of Ca and Mg
Increased renal prostaglandins
Increased venous capacitance

28

What are the side effects of furosemide?

Hypokalemia and disorders in pH, mostly alkalosis (because of H excretion)
Elevated BUN, hyperglycemia or hyperuricemia
kidney stones
Ototoxicity(!!!!), sialadentitis

29

What are drug intrx of furosemide?

Interactions with Li (bipolar)
Indomethacin (pg inh)
probenecid
warfarin (competes with warfarin so could double warfarin concentration)

30

When do you use bumetanide?

Furosemide substitute in pts receiving warfarin

31

What is significant about torsemide?

Loop diuretic that also lowers bp

32

What two types of Na channels are expressed in IMCD

amiloride-sensitive cylce nucleotide gated cation CNG channel
Low conductance highly-selective Na ENaC channel

33

What is the most popular diuretic?

Thiazide diuretics

34

What is the mechanism of action of thiazide diuretics

Inhibit NaCl reabsorption in the Na-K aldosterone-independent segment of the DCT

35

What are the pharmacological effects of THiazide Diuretics?

Moderate loss of Na, K and Cl, cause 3x increase in urine flow
Sodium loss results in reduced GFR
Elevation of excreted urinary potassium (hypokalemia)
Increase excretion of titratable acid, due to increased delivery of Na to distal tubule
Decresae urinary excretion of Ca (DIFFERENCE WITH LOOP DIURETICS)
Increase the urinary excretion of Mg

36

What are the therapeutic uses of thiazide diuretics?

diuretic to reduce edema with CHF, cirrhosis, and nephrotic syndrome
hypercalciurea and renal calcium stones
reduce bp in essential htn
osteoporosis
nephrogenic diabetes insipidus

37

What is a similarity in adminstration efx of thiazide diuretics and loop diuretics?

both must be taken into the nephron and attack channels from the inside

38

Whats the difference between class I and class II thiazide diuretics?

Class I used when gfr > 50ml/min
Class II when GFR 30

39

What is the most common thiazide diuretic?

Class I and hydrochlorothiazide

40

What is the big class II thiazide diuretic?

Metolazone (10X more potent than hydrochlorothiazide

41

What are all the class I thiazide diuretics?

hydrochlorothiazide
chlorthalidone
quinethazone

42

What are all the class II thiazide diuretics?

metolazone
indapamide

43

What are the adverse reactions of thiazides?

From Depletion:
hypoK, hypoCL alkalosis, hypoMg

From retention:
hyperuricemia, hyperCal,

Metabolic Changes:
hyperglycemia

44

What type of cells are found in the late DCT and CD?

Principal cells

45

What is the difference between two types of principal cells?

Type A hormonally responsive
Type B load responsive

46

Which type, A or B, of principal cell is involved in Na reabsorption and K secretion?

Type A, hormonally regulated by aldosterone

47

What are considered the holy grail of diuretics?

aldosterone antagonists

48

What are the mechanisms of action of aldosterone antagonists?

bind to aldosterone receptor in the cytoplasm and prevent its translaocation to the nucleus
reduce ENaC channels that are involved in Na reabsorption

49

What are the net effects of aldosterone antagonists?

increase urinary excretino of Na and inhibit secretion of K (k-sparring)

50

What is the major aldosterone antagonist?

spironolactone

51

What is spironolactone metabolized to?

canrenone

52

What are the side effects of aldosterone antagonists?

hyperkalemia
gynecomastia (has intxn with androgen receptor as well)

53

Why do you use eplenerone instead of spironolactone?

Expected to have less side effects because it has very low affinity from androgen receptors compared to spironolactone

54

What are the clinical uses of spironolactone/aldosterone antagonists?

diuretic, usually in combo with HCTZ
tx of chf cirrhosis

55

What are additional k-sparing diuretics?

triametrene and amiloride

56

What are the moa of triametrene & amiloride?

inhibit na reabsorption in the late distal tubule

57

what are the pharmacological efx o k-sparing diuretics?

increase urinary excretion of na and decreased secretion of k and h

58

what hematologic disorder do you see with k-sparing diuretics?

megaloblastic anemia in pts with cirrhosis

59

What are Atrial Natriuretic Peptides?

Inhibitors of the nonspecific Na Channel

60

What is the mechanism of ANP?

ANP produced in response to stretch.it binds to NP receptor, and increases cGMP. BNP is produced by the ventricle, BNP also binds to NPRA and acts like ANP, CNP binds to NPRB in vasclar smooth muscle cells and mediates relaxation

61

What are examples of ANP?

nesiritide recombinant b-type NP

62

what are the clinical effects of anp?

increase Na excretion by iNH CNG-nonspecific cation channel in IMCD
Renin-angiotensin system and endothelin production

63

The rest of the cards are from his summary slides

yes

64

Diuretics with what two things have been shown to be useful in management of hypertension?

Beta-blockers and ACEis

65

Patients with edematous conditions such as ________ frequently require the use of a diuretic for optimal control of BP

heart failure and renal insufficiency

66

What are thiazides widely used to treat?

mild or moderate HTN

67

What is the most popular drug for therapy for high BP?

HCTz

68

What are two drugs that may help with impaired renal function when thiazides are not?

metolazone and indapamide, usually not effective when gfr lower than 30

69

A poor response to thiazides may reflect what about their htn?

they may have an overwhelming load of dietary sodium or an impaired renal capacity to excrete the sodium

70

Are loop diuretics more or less efficient than thiazides?

more efficient

71

When do you use loop diuretics?

severe hypertension

72

Do loop diuretics have more or less side efx than thiazides?

more because they are also more effective, so you ahve to worry about extreme natriuresis

73

What is a very common preventable side effect of loop diuretics and what do you ahve to avoid?

Avoid coadministration with NSAIDs because it can lead to diuretic resistance.
1) PGs reduce Na reabsorp
2) antagonize ADH
3) distribute renal blood from the cortex to the juxtaglomerulus

74

What is the only diuretic that does not cause increased uric acid?

aldosterone antagonists

75

Are k-sparing diuretics helpful in patients with hyperuricemia?

yes

76

What is the drug of choice in cirrhosis?

spironolactone

77

Are K-sparing diuretics stronger than, equal to or weaker than thiazides as an antihypertensive?

equal to