Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Renal > Lecture 14: Diuretics + Antidiuretics > Flashcards

Lecture 14: Diuretics + Antidiuretics Flashcards

1
Q

Define diuresis and natriuresis

A

Diuresis:
Inc. in urine flow rate

Natriuresis:
Inc. excretion of Na + anions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List the four major classes of diuretics

A

CA inhibitors (CAIs)

Loop diuretics (LDs)

Thiazides diuretics (TZs)

K+ sparing diuretics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What do each class of diuretics inhibit?

A

CA inhibitors:
Inhibit H+ secretion in PT

Loop diuretics:
Inhibit NKCC2 in thick AL

Thiazide diuretics:
Inhibit NCC in DCT

K+ sparing diuretics:
Inhibit ENaC in CNT/CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is an example of carbonic anhydrase inhibitors?

A

Acetazolamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are examples of loop diuretics?

A

Furosemide

Bumetanide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are examples of thiazide diuretics?

A

Hydrochlorothiazide

Chlorthalidone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are examples of K+ sparing diuretics?

A

Triamterene

Amiloride

Sprironolactone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the max acute decrease in sodium reabsorption that can occur following administration of

CAIs
LDs
TZs
K sparing diuretics

A

Loop = 25%

Thiazides = 5-8%

CA inhibitors = 5%

K sparing = 1-2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the mechanism for TRIAMTERENE and AMILORIDE blocking ENaC?

How about for Spironolactone?

A

Directly block ENaC

Spironolactone: competitive inhibition of aldo binding to MR
(Very effective in patients with high aldosterone, not effective in patients with low aldo)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do diuretics get into tubular fluid?

A

Enter TF mainly via tubular secretion, where OAT family transporters help

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe mechanisms for natriuresis

CAIs
LDs
TZs
K-sparing

A

CAIs =
Inhibit H+ secretion in PT

LDs =
Inhibit NKCC2 in thick AL

TZs =
Inhibit NCC in DCT

K-sparing =
Inhibit ENaC in CNT/CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe mechanism for diuresis

A 
Dec. Na reabsorption 
=
More particles remaining in tubular fluid 
=
Dec. water reabsorption 
=
Inc. urine flow rate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Explain the importance of the diuretic breaking phenomenon

A

Compensatory mechanism to restore sodium balance with chronic use of diuretics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does diuretic breaking involve?

A

Activation of symp division

Activation of RAAS

Other mechanisms
+ load dependence of sodium reabsorption
+ dec. BP = dec. pressure natriuresis
+ dec. natriuretic hormones
+ inc. expression of transporters in tubular epithelial cells
+ hypertrophy of tubular epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is a consequence of even a brief period of negative Na balance?

A 
Dec. total body Na
=
Dec. ECF 
=
Dec. ECV
(The part of the ECF that can activate mechanisms to induce changes in sodium excretion)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the key for activating diuretic braking mechanism?

A

Dec. ECV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the effect of dec. ECV on BP?

A

Dec. ECV = dec. BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What results from dec. BP after fall in ECV?

A

(1) arterial BRs = reflex inc. sympathetic tone to kidneys

(2) dec. stretch of afferent arterioles will stimulate renal BRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Besides drop in BP, what else will reduce stretch of AA in kidney?

A

Reflex inc. sympathetic tone to kidneys

By constricting AA via alpha1 stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are consequences of inc. sympathetic tone to kidneys?

A

1) constriction of AA via alpha1 receptor stimulation
2) inc. renin secretion via stimulation of beta1 receptors on granular cells
3) inc. Na reabsorption in PT by increasing NHE (Na/H exchange)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What factors following diuretic therapy will lead to increased renin secretion?

A

1) dec. stretch of AA as sensed by renal BRs
2) beta1 sympathetic stimulation
3) dec. Na delivery to macula densa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are consequences of more sodium reabsorption in PT following diuretic therapy and increased symp tone?

A

1) reduced Na dlievery to macula densa

2) dec. sodium excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is effect of inc. renin secretion on AngII?

A

Inc. renin = inc. AngII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are consequences of inc. AngII following diuretic therapy?

A

1) inc. Na reabsorption in PT by stimulating more Na/H exchange
2) stimulate AT1 receptor to inc. Aldo secretion
3) inc. Na reabsorption in DCT, CNT/CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are effects of increased aldosterone secretion?

A

Increased Na reabsorption in CNT/CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What mechanisms contribute to reduction in sodium excretion

AKA restoration of Na balance via diuretic breaking

A

(1) inc. Na reabsorption in DCT, CNT/CD
(From AngII)

(2) inc. reabsorption in CNT/CD
(From aldo)

(3) inc. Na reabsorption in PT + DCT
(From symp tone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Where does all regulation of potassium excretion occur?

A

CNT/CD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How does inc. Na reabsorption in CNT/CD lead to increased K secretion?

A 
Inc. Na reabsorption via ENaC
=
Inc. electrochemical gradient for K secretion
=
Inc. K secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Describe effect of CAIs, LDs, and TZs on potassium excretion

A 
All inc. sodium delivery to CNT/CD by inhibiting Na reabsorption proximal to CNT/CD
=
Inc. Na reabsorption in CNT/CD
=
Inc. electrochemical gradient for K secretion
=
Inc. K secretion in CNT/CD
=
Inc. K excretion 
(common AE of hypokalemia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What effect does increased flow through CNT/CD have on K?

A

Further enhances electrochemical gradient by washing away secreted K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Describe effect of K-sparing diuretics on K excretion

A 
Dec. Na reabsorption in CNT/CD by inhibiting ENaC 
=
Dec. electrochemical gradient for K secretion
=
Dec. K secretion in CNT/CD
=
Dec. K excretion
(Potential AE: hyperkalemia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What other drugs spare potassium?

A

ACEIs

ARBs

Trimethoprim
(Related to triamterene)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How do CA inhibitors affect H+ and HCO3?

A 
Dec. H+ secretion in PT by inhibiting CA
=
Dec. HCO3 reabsorption in PT
= 
Inc. bicarbonate excretion
Common adverse effect:
Metabolic acidosis (which limits ability of carbonic anhydrases because if pH is low enough, they aren't needed as much!)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is effect of LDs and TZs on H+ and HCO3?

A 
Both inc. sodium delivery to CNT/CD by inhibition Na reabsorption proximal to CNT/CD
=
Inc. Na reabsorption in CNT/CD
=
Inc. electrochemical gradient for H+ secretion
=
Inc. H+ secretion in CNT/CD
=
More new HCO3 made

Common AE = metabolic alkalosis

35
Q

What are effect of K-sparing diuretics on H+ and HCO3?

A 
Dec. Na reabsorption in CNT/CD by inhibiting ENaC 
=
Dec. electrochemical gradient for H+ secretion 
=
Dec. H+ secretion in CNT/CD
=
Dec. HCO3 reabsorption in CNT/CD
=
Inc. HCO3 excretion

(Potential AE: metabolic acidosis)

36
Q

What are requirements for concentrating urine mechanism?

A

1) ADH

2) medullary gradient

37
Q

What does formation and maintenance of medullary gradient require?

A

NaCl reabsorption in thick AL by NKCC2

Which is the transporter that Loop diuretics block

38
Q

What effect do loop diuretics have on concentrating mechanism?

A

Markedly impair concentrating mechanism by completely abolishing medullary gradient

39
Q

What are requirements for formation of a dilute urine?

A

1) no ADH

2) delivery of hypo-osmotic TF to CNT/CD
- have NaCl reabsorption in thick AL by NKCC2
- minor way to assure: block NaCl reabsorption by NCC in DCT

40
Q

What effect do LDs have on diluting mechanism?

A

Markedly impair diluting mechanisms

Smaller impairment with thiazides

41
Q

What is mannitol ?

A

Osmotic diuretic that produces both diuresis and natriuresis

42
Q

How do osmotic diuretics work?

A 
Dec. water reabsorption in PT
=
Dec. sodium in tubular fluid in PT
=
Dec. sodium reabsorption in PT
43
Q

What is the maximum amount osmotic diuretics can dec. Na reabsorption ?

A

20%

44
Q

What are examples of aquaretics?

A

ADH antagonists (“Vaptans”) = most selective:
Conivaptan
Tolvaptan

Demeclocycline

Lithium

45
Q

How do aquaretics work?

A

Produce diuresis ONLY

Vaptans selective for V2 receptor

46
Q

What are effects of V1A and V2 receptors?

A

V1A = Gq
Vasoconstriction

V2 = Gs
Anti-diuretic effects, urea permeability

47
Q

In what conditions does edema most commonly occur?

A

HF

Cirrhosis

Kidney disease

48
Q

What are therapeutic uses of diuretics?

A

Edema

Non-edema:
HTN
Nephrolithiasis
Hypercalcemia
Nephrogenic diabetes insipidus
49
Q

Which diuretics are used for HTN?

A

Thiazides

50
Q

What is a difference between chlorthalidone and hydrochlorothiazide?

A

Chlorthalidone = more potent, longer duration of action in maintaining low BP throughout 24 hours

51
Q

What is nephrolithiasis?

A

Kidney stones

52
Q

Why use a thiazides for kidney stones?

A

Decrease calcium excretion b/c many patients with these Ca-containing kidney stones got it from inc. calcium excretion

Tx:
Thiazide cause mild volume depletion
=
Inc. Na reabsorption in PT
=
More calcium reabsorption in PT
=
Dec. calcium excretion
53
Q

What usually causes hypercalcemia?

A

Inc. PTH

54
Q

What is a possible treatment for hypercalcemia?

A

Inc. calcium excretion with a loop diuretic:

LD inhibits NKCC2 in thick AL
=
Dec. lumen positive TEP in thick AL
=
Dec. paracellular Ca reabsorption in thick AL
=
Inc. calcium excretion
55
Q

What is an ADH congener?

A

Anti-diuretic

56
Q

What is treatment for central DI ADH deficiency?

A

Replace ADH with an ADH congener (antidiuretic)

57
Q

What does nephrogenic DI mean?

A

Nephrons failing to respond to ADH

58
Q

How can you treat genetic and acquired nephrogenic DI?

A

Genetic:
Thiazides

Acquired:
Thiazides
Amiloride

59
Q

What kind of therapy could be recommended to a patient with severe edema due to HF?

A

Start patient on LD

Add thiazide for more natriuresis

Add K-sparing diuretic for even more natriuresis

60
Q

What AEs could be prevented or attenuated by adding K-sparing diuretic to LD/TZ?

A

Hypokalemia

Metabolic alkalosis

61
Q

What is the most common use of K sparing diuretics?

A

In combo therapy with LD or TZ in order to:

Inc. natriuresis
Dec. hypokalemia
Dec. metabolic alkalosis

62
Q

What is the main instance in which K-sparing diuretics are used alone?

A

In patients with high aldosterone

63
Q

What are therapeutic uses of CAIs?

A

Acute mountain sickness

Glaucoma

64
Q

What are osmotic diuretics used for?

A

To shift fluid from IC to EC compartment

Cerebral edema (IC edema)
Dialysis
Crush injuries
Glaucoma

65
Q

What are aquaretics used for?

A

Syndrome of inappropriate ADH secretion (SIADH)

Hypervolemic hyponatremia

66
Q

What is SIADH?

A

Syndrome of inappropriate ADH secretion

ADH secreted at level that is inappropriate for patient’s volume and osmolality status, resulting in hyponatremia

67
Q

What are predictable AEs from diuretics?

A

K+ abnormalities

Acid-base disorders

Ca abnormalities

Hyponatremia
Hypomagnesemia
Hyperuricemia

And others

68
Q

What predictable AE are caused by CAIs?

A

Hypokalemia

Metabolic acidosis

Nephrolithiasis

69
Q

What predictable AEs are caused by LDs?

A

Hypokalemia

Metabolic alkalosis

Hypocalcemia
Hyponatremia
Hypomagnesemia

Hyperuricemia

Hypovolemic, postural hypotension

70
Q

What predicable AEs are caused by thiazides?

A

Hypokalemia

Metabolic alkalosis

Hypercalcemia
Hyperuricemia

Hyponatremia
Hypomagnesemia

Hypovolemic, postural hypotension

71
Q

What AEs are caused by K-sparing diuretics?

A

Hyperkalemia

Metabolic acidosis

(Spironolactone: gynecomastic, ED)

72
Q

What AEs result from mannitol?

A

Pulmonary edema in patients with decreased LV function

73
Q

What AEs are not predictable?

A

Hyperglycemia =
Thiazides, loop diuretics

Hyperlipidemia =
Thiazides, loop diuretics

Ototoxicity =
Loop diuretics

Rashes, etc…. any drug!

74
Q

In what nephron segment does Bartter’s syndrome effect?

What transporters/channels are abnormal?

A

Thick AL

NKCC2
ROMK
Cl channels
Barttin subunit
CaSR
75
Q

What abnormalities are characteristic of Bartter’s syndrome?

What drug does it mimic?

A

Hypokalemia

Metabolic alkalosis

Hypercalciuria

Impaired concentrating mechanism

Mimics loop diuretics

76
Q

What nephron segment does Gitelman’s syndrome affect?

What transporters/channels are abnormal?

A

DCT

NCC

Cl channels (CLC-KB)

77
Q

What abnormalities are characteristic of Gitelman’s syndrome?

What drug does it mimic?

A

Hypokalemia

Metabolic alkalosis

Hypocalciuria

Normal concentrating mechanism

Mimics thiazides

78
Q

What nephron segment does pseudohypo-aldosteronism affect?

What transporters/channels are abnormal?

A

CNT/CD

Mineralocorticoid receptor

79
Q

What abnormalities are characteristic of pseudo-hypoaldosteronism?

What drug does it mimic?

A

Hyperkalemia

Hypovolemic

Mimics K-sparing diuretics

80
Q

Why is synthetic ADH seldom used as an antidiuretic?

A

Prominent vasoconstrictor effects!

81
Q

Name an ADH congener

A

Desmopressin

82
Q

What is desmopressin used for?

A

Central DI

Nocturnal enuresis
Bed-wetting

83
Q

What is an advantage of desmopressin vs. synthetic ADH?

A

Desmopressin has minimal V1A agonist activity = minimal vasoconstriction !!!

Renal (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions