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Flashcards in Diuretics Deck (89):
1

PCT
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here

1. responsible for 60-70% of total reabsorption of NA
2. carries out isosmotic reabsorption of AA, glucose & many cations
3. major site for reabsorption of Sodium Chloride& Bicarb

b) NHE3: apical membrane Na/H exchange via NHE3
Na/K ATPase is present in the basolateral membrane to maintain intracellular Na & K

c) Carbonic Anhydrase: bicarbonate is reabsorbed poorly through luminal membrane so it is converted to CO2 & H2O by Carbonic Anhydrase

2

TAL
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here

1. responsible for absorption of 20-30% of Na
2. pumps out Na, K, Cl into interstitium
3. major site for Mg & Ca reabsorption: positive potential in lumen allows Mg2+ and Ca2+ to be reabsorbed via paracellular pathway

b) NKCC2: reabsorption of Na, Cl & K via Na+/K+/2Cl- cotransporter

3

DCT
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here

1. reabsorption of 5-8% of Na
2. actively pumps Na & Cl out of lumen via Na+/Cl- cotransporter NCC
3. Ca also reabsorbed under control of PTH

b) NCC: actively pumps Na & Cl out of lumen (Na+/Cl- cotransporter)

c)

4

CD
a) Major things reabsorbed here
b) main membrane transporter invovled
c) enzyme involved here

1. reabsorption of 2-5% of Na--last tubular site for Na reabsorption
2. controlled by aldosterone, occurs via channels & is accompanied by equal loss of K or H ions
3. primary site of acidification of union & K excretion
4. Cl- reabsorbed via paracellular pathway because of negative lumen potential

b) ENaC: inward diffusion of Na via the epithelial sodium channel ENaC leaves lumen negative potential--> drives reabsorption of Cl- & efflux of K+

5

Carbonic Anhydrase Inhibitors

1. acetazolamide
2. dorzolamide

6

Loop Diuretics

1. Furosemide
2. Bumetanide
3. Torsemide

7

Thiazides

1. Hydrochlorothiazide

8

Potassium Sparing Diuretics

1. aldosterone antagonists: spironolactone & eplerenone
2. Na channel Blockers: amiloride & triamterene
3. ADH antagonists: Lithium & demeclocycline

9

Osmotic Diuretics

Mannitol

10

Acetazolamide

Carbonic Anhydrase inhibitor

11

Where do Carbonic Anhydrase Inhibitors Act

the PCT

12

Acetazolamide MOA & Effects & uses

inhibit CA both in the brush border & intracellular CA in PCT

Effects:
1. Bicarbonate diuresis-->metabolic acidosis results
2. Increased Na is presented to the CCD, where it is absorbed so more K is excreted-->causes significant K loss in urine--> HYPOKALEMIA
3. CA inhibition in ciliary epithelium -->reduced secretion of aqueous humor

Uses:
1. glaucoma
2. urinary alkalinization for acidic drug toxicity
3. tx acute mountain sickness
4. significant metabolic alkalosis

13

drug used in high altitude sickness (mountain sickness)

acetazolamide (CA inhibitor)

acidosis of CSF results in hyperventilation

14

Uses of CA inhibitors

1. glaucoma
2. urinary alkalinization for acidic drug toxicity is salicylates
3. tx acute mountain sickness
4. significant metabolic alkalosis

15

Adverse Effects of Carbonic Anhydrase Inhibitors

1. cross algernicity with other sulfonamides
2. hyperchloremic metabolic acidosis
3. renal stones: alkalization of urine by these drugs may cause Ca to precipitate -->renal stones
4. Hypokalemia

16

How can CA inhibitors be used to treat glaucoma

CA inhibition in the ciliary epithelium -->reduced secretion of aqueous humor

17

Where do Loop Diuretics act?

Thick ascending limb

18

Furosemide

Loop Diuretic

19

Furosemide MOA & Effects & uses & ADR

Loop Diuretic, acts in TAL

1. Inhibits NKCC2 (Na+/K+/2Cl- cotransporter)-->produce massive NaCl diuresis-->Edema fluid is rapidly excreted & blood volume is significantly reduced.

The Loop of Henle is the diluting segment, so blocking its function-->reduced ability to dilute urine

2. also results in loss of lumen positive potential-->decreased reabsorption of ions like Ca & Mg-->Ca excretion is significantly increased

3. More Na is presented to the CD-->it's reabsorbed in exchange for K+ & H+-->hykalemic alkalosis

Uses:
1. Tx of edematous states including HF & ascites
2. *tx of acute pulmonary edema (LVF)
3. mild to moderate CHF
4. severe hypercalcemia
5. seen commonly in malignancy (so we give large doses of furosemide with fluids & electrolytes)

ADR:
1. *Hypokalemia--usually given with K sparing drugs
-------->Hypokalemic metabolic alkalosis
2. Hypomagnesemia
3. Hypocalcemia
4. Hypovolemia
5. *Ototoxicity--> don't combine with other ototoxic drugs i.e. aminoglycosides
6. cross hypersensitivity with sulfa drugs--> i.e. if allergic to sulfa drugs don't use bc may also be allergic

20

Uses of Loop Diuretics

1. Tx of edematous states including HF & ascites
2. *tx of acute pulmonary edema (LVF)
3. mild to moderate CHF
4. severe hypercalcemia
5. seen commonly in malignancy (so we give large doses of furosemide with fluids & electrolytes)

21

ADR of Loop Diuretics

1. *Hypokalemia--usually given with K sparing drugs
-------->Hypokalemic metabolic alkalosis
2. Hypomagnesemia
3. Hypocalcemia
4. Hypovolemia
5. *Ototoxicity--> don't combine with other ototoxic drugs i.e. aminoglycosides
6. cross hypersensitivity with sulfa drugs--> i.e. if allergic to sulfa drugs don't use bc may also be allergic

22

Site of action of Thiazides

Distal Convoluted Tubule

23

Hydrochlorothiazide

MOA

Uses

ADR

Thiazide, acts in Distal convoluted tubule

MOA: inhibits Na/Cl transporter (NCC) in early segment of distal convoluted tubule

Uses:
1. HTN (Mild-moderate essential HTN)
2. Chronic renal calcium stone (bc reduce urine Ca concentration)

ADR:
1. severe hyponatremia
2. hypokalemia
3. cross hypersensitivity w sulfonamides
4. hyperuricemia-->gout
(direct competition of thiazides for rate transport)
5. Hyperlipidemia-->increase serum CH & LDL 5-10%
6. Hyperglycemia due to diminished insulin secretion in patient with preexisting type 2 diabetes

24

Effects of Thiazides

1. sustained Na & Cl Diuresis

reduction in transport of Na into tubular cell reduces intracellular Na -->promotes Na/Ca exchange
------->results in increased reabsorption of Ca from urine -->urine Ca content is decreased

2. Reduces BP

initially decrease CO bc decrease blood volume, but later decrease TPR bc decrease Na concentration & Na is responsible for maintaining vessel stiffness.

25

Uses of Thiazides

1. HTN (Mild-moderate essential HTN)
2. Chronic renal calcium stone (bc reduce urine Ca concentration)

26

Thiazides ADR

1. severe hyponatremia
2. hypokalemia
3. cross hypersensitivity w sulfonamides
4. hyperuricemia-->gout
(direct competition of thiazides for rate transport)
5. Hyperlipidemia-->increase serum CH & LDL 5-10%
6. Hyperglycemia due to diminished insulin secretion in patient with preexisting type 2 diabetes

27

Potassium sparing Diuretics act in the

Collecting Duct

28

Downside of Potassium sparing diuretics & compensation

Weak therefore rarely used alone; Exception = hyperaldosteronism

29

Spironolactone

Aldosterone antagonist; K+ sparing diuretic

30

Amiloride & Triamterene

K+ Sparing Diuretics that directly block Na channels in CD

31

How do K+ Sparing Diuretics work

Inward diffusion of Na via epithelial sodium channel levels a lumen-negative potential which drives reabsorption of Cl- & efflux of K+

32

Spironolactone MOA, Effects, Uses, ADR

Antagonist of Aldosterone in Collecting Duct

MOA: by binding & blocking the aldosterone receptor-->reduce expression of genes controlling synthesis of epithelial Na ion channels & Na/K ATPase-->this increases sodium excretion bc less Na is being reabsorbed

Effects:
1. increases Na excretion
2. Decreases K+ & H+ ion excretion (bc whenever Na is reabsorbed K is exchanged & excreted
3. may cause hyperkalemic metabolic acidosis

Uses:
1. Hypokalemia causes by loop diuretics & thiazides
2. Aldosteronism (occurs in cirrhosis; also seen in Conn's syndrome & with late HF

ADR:
1. Hyperkalemia-->can cause cardiac arrest
2. Extreme caution needed when given with ACE-inhibitors bc both inhibit aldosterone
3. gynecomastia (painful, enlargement of breast in males) hirsutism (excess body hair growth), loss of libido & impotence
--->all from anti-androgenic effects

33

gynecomastia (painful, enlargement of breast in males) hirsutism (excess body hair growth), loss of libido & impotence

all from anti-androgenic effects of spironolactone

34

Osmotic diuretics work where

PCT (where majority of isosmotic reabsorption occurs)

35

Mannitol

Osmotic diuretic; acts in PCT; given by IV
freely filtered in glomerulus but poorly reabsorbed, so it remains in the lumen

Holds water by virtue of its osmotic effect

36

Mannitol Effects & uses

Effects:
1. urine volume is increased
2. Can decrease intracranial pressure by osmotically extracting water fro tissue into blood
3. similar effect in eye (reduces IOP)

Uses:
1. Cerebral Edema
2. Glaucoma

37

Amiloride

K+ sparing diuretic used in lithium-induced diabetes insidious bc prevents lithium's action on CD (Li acts like & replaces Na)

38

Dorzolamide MOA

inhibition of CA in PCT

39

Urinary Electrolytes in Acetazolamide

Increase Na
Increase K
VERY increased HCO3

40

Urinary Electrolytes in Dorzolamide

Increase Na
Increase K
VERY increased HCO3

41

Blood Chemistry & pH in Acetazolamide

1. hypokalemia
2. acidosis (low pH)
3. Hyperchloremia

42

Blood Chemistry & pH in Dorzolamide

1. hypokalemia
2. acidosis (low pH)
3. Hyperchloremia

43

Ethacrynic acid MOA

Inhibition of Na/K/2Cl cotransporter in TAL

44

Furosemide MOA

Inhibition of Na/K/2Cl cotransporter in TAL

45

Torsemide MOA

Inhibition of Na/K/2Cl cotransporter in TAL

46

Urinary Electrolytes in Ethacrynic acid

1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3

47

Urinary Electrolytes in Furosemide

1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3

48

Urinary Electrolytes in Torsemide

1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3

49

Blood Chemistry & pH in Ethacrynic acid

1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia

50

Blood Chemistry & pH in Furosemide

1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia

51

Blood Chemistry & pH in Torsemide

1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia

52

Hydrochlorthiazide MOA

Inhibition of Na/Cl cotransporter in DCT

53

Indapamide MOA

Inhibition of Na/Cl cotransporter in DCT

54

Metolazone MOA

Inhibition of Na/Cl cotransporter in DCT

55

Thiazides

1. Hydrochlorthiazide
2. Indapamide
3. metolazone

56

Loop Diuretics

1. Furosemide
2. Torsemide
3. Ethacrynic acid

57

K+ sparing Diuretics

1. Amiloride (blocks Na channels in CD)
2. Triamterene (blocks Na channels in CD)
3. Spironolactone (blocks aldosterone receptors in CD)

58

Thiazides Urinary Electrolytes

1. Increased Na, K, Cl
2. Decreased Ca

59

Thiazides Blood Chemistry & pH

1. hypokalemia
2. alkalosis (increased pH)
3. HYPERcalcemia
4. Hyperuricemia
5. Hyper glycemia

60

Loop Diuretics Blood Chemistry & pH

1. hypokalemia
2. alkalosis (increased pH)
3. hypocalcemia
4. hypomagnesemia

61

Loop Diuretics Urinary Electrolytes

1. Very increased Na
2. Increased K
3. Increased Ca
4. Increased Mg
5. Increased Cl
6. DECREASED HCO3

62

K+ Sparing Diuretics Urinary Electrolytes

1. Small amounts of Na
2. decreased K

63

K+ Sparing Diuretics Blood Chemistry & pH

1. Hyperkalemia
2. acidosis (decreased pH)

64

Diuretics that result in acidosis (pH)

1. CA inhibitors: acetazolamide & dorzolamide
2. K+ sparing diuretics

65

Diuretics that result in alkalosis (pH)

1. Loop Diuretics
2. Thiazides

66

MOA of Spironolactone

Blocks Aldosterone receptors in CD

67

MOA of triamterene

Blocks Na channels in CD

68

MOA of Amiloride

Blocks Na channels in CD

69

Best Diuretic for edema

Furosemide

70

Best for HTN & as anti-diuretic

Thiazides

71

Best to tx nephrolitiasis with hypocalcemia

thiazides

72

best to treat glaucoma

acetazolamide & mannitol

73

best to treat cerebral edema

mannitol--NEVER USED IN CF

74

Increases risk of HYPERkalemia seen with K sparing diuretics

1. NSAIDS
2. Beta blockers
3. ACE-I

75

Reduces Digoxin toxicity

K sparing diuretics

76

Increases Digoxin toxicity

loop & thiazides

77

reduces efficacy of diuretics by inhibiting secretion into renal tubule

Probenecid

78

DOC in CCF

Thiazide

79

DOC in Hepatic ascites

Thiazides with K+ supplements or
Thiazides with K+ sparing diuretics

80

DOC in Pulmonary Edema of Cardiac origin (LVF)

Loop Diuretics

81

DOC in increased intracranial pressure

osmotic diuretics

82

DOC in renal edema--nephrotic syndrome

Thiazide & K-sparing or
loop & K-sparing

83

DOC in Chronic Renal Failure

Loop Diuretics

84

DOC in acute renal failure

osmotic diuretics

85

Vasopressin & Desmopressin

What?
MOA
Effects
Used to Tx

Antidiuretic Hormone Agonists

MOA:
1. facilitates H20 reabsorption from CD by activation of V2 receptors (Gs)
2. increased cAMP-->insertion of additional aquaporin water channels into the luminal membrane of the tubule--> facilitates water reabsorption

Effects: reduce urine volume & increase it's concentration

Used: in Neurogenic (pituitary) Diabetes Insipidus

86

DOC in Neurogenic (pituitary) Diabetes Insipidus

Vasopressin or Desmopressin

87

Demeclocycline

ADH Antagonist

MOA:
1. oppose the actions of ADH & other peptides with act on V2 receptors
2. such peptides are secreted by certain tumors (i.e. small cell carcinoma of the lung) and cause significant water retention & hyponatremia

This is syndrome of inappropriate ADH secretion (SIADH)

Remember: V2 receptors act through Gs-->increased cAMP-->insertion of additional aquaporin water channels into the luminal membrane of the tubule--> facilitates water reabsorption

88

Conivaptan

ADH antagonist

MOA:
1. oppose the actions of ADH & other peptides with act on V2 receptors
2. such peptides are secreted by certain tumors (i.e. small cell carcinoma of the lung) and cause significant water retention & hyponatremia

This is syndrome of inappropriate ADH secretion (SIADH)

Remember: V2 receptors act through Gs-->increased cAMP-->insertion of additional aquaporin water channels into the luminal membrane of the tubule--> facilitates water reabsorption

89

DOC for syndrome of inappropriate ADH secretion (SIADH)

Demeclocycline & conivaptan