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Flashcards in Diuretics Deck (144):
1

metabolic acidosis as SE

Sulfanilamide

2

prototype drug

Acetazolamide

3

- limited usefulness as diuretics

CAIs

4

- forerunners of diuretics

CAIs

5

Zn metalloenzyme found in proximal tubular epithelial cells (where too??)

Carbonic Anhydrase

• Luminal and basolateral membranes (type IV)
• Cytoplasm (type III)

6

first to discover CA in mammalian kidneys

Davenport and Willhelmi (1941)

7

Key role in NaHCO3 reabsorption and acid secretion

Carbonic anhydrase

8

Inhibit the enzyme carbonic anhydrase, blocking NaHCO3 reabsorption in PCT

Carbonic anhydrase Inhibitors MOA

9

MOA of Carbonic Anhydrase Inhibitors

Inhibit the enzyme carbonic anhydrase, blocking NaHCO3 reabsorption in PCT
collecting duct as secondary site of action (blocking and secretion)

10

collecting duct as secondary site of action (blocking and secretion)

MOA of Carbonic Anhydrase Inhibitors

11

Extrarenal action of CAIs

Extrarenal actions:
1. Decreases rate of formation of aqueous humor -> reduces IOP
2. Frequently causes paresthesias and somnolence
3. Anticonvulsant (acetazolamide)
4. Increases CO2 levels in peripheral tissues; decreases CO2 levels in expired gas
5. Reduce gastric acid secretion (large doses)

12

Decreases rate of formation of aqueous humor -> reduces IOP

CAIs

13

Frequently causes paresthesias and somnolence

CAIs

14

Anticonvulsant

acetazolamide

15

Increases CO2 levels in peripheral tissues; decreases CO2 levels in expired gas

CAIs

16

Reduce gastric acid secretion (large doses)

CAis

17

Dose Acetazolamide

125 mg half, 250 mg and quarter-scored tablets

18

1% ophthalmic suspension

Brinzolamide

19

2% ophthalmic suspension

Dorzolamide

20

primary indication is Glaucoma, no diuretic effect, no systemic effect and ↓IOP

Brinzolamide, Dorzolamide Topical agents

21

open-angle glaucoma

CAIs

22

CHF-associated and drug induced edema

acetazolamide

23

Epilepsy

(acetazolamide)

24

symptomatic relef and/or prophylaxis for acute mountain or altitude sickness

CAIs
*used nightly for 5 days before climbing to prevent weakness, breathlessness

25

familial periodic paralysis

CAIs

26

correction of metabolic alkalosis (diuretic-induced H+ excretion)

CAIs

27

bone marrow depression, skin toxicity, sulfonamide-like renal lesions, hypersensitivity reactions (SJS)

AE - CAIs

28

signs on bulla skin, deadly if on mucosa

SJS

29

drowsiness and paresthesias

AE - CAIs

30

Hepatic encephalopathy

AE - CAIs

31

( diversion of ammonia of renal origin from urine into the systemic circulation -> induce or worsen hepatic encephalopathy therefore drugs are contraindicated to patients with hepatic cirrhosis

AE - CAIs

Hepatic encephalopathy

32

calculus formation, ureteral colic

AE - CAIs

33

(owing to ppt of calcium phosphate salts in an alkaline urine)

AE - CAIs
Calculus formation, ureteral colic

34

worsening of metabolic or respiratory acidosis

AE - CAIs

35

Drugs are contraindicated in patients with hyperchloremic acidosis or severe COPD

AE - CAIs
worsening of metabolic or respiratory acidosis

36

Na+ and K+ wasting

AE - CAIs

37

CI for patients w/ Na+ or K+ depletion)

AE - CAIs
CI for patients w/ Na+ or K+ depletion)

38

- Most effective diuretics available

LOOP DIURETICS

39

- High-ceiling diuretics

LOOP DIURETICS

40

Highest efficacy in mobilizing Na+ and Cl- from the body

LOOP DIURETICS

41

*produce copious amounts of urine

LOOP DIURETICS

42

Act directly on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption

LOOP DIURETICS

43

MOA of Loop diuretics

Act directly on the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption

44

Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance (↑ renal blood flow)

LOOP DIURETICS

45

– impt role in mediating renin release reponse to loop diuretics

Prostacyclins
LOOP DIURETICS

46

Prostaglandins have a role in their diuretic action and NSAIDS like indomethacin that interfere in prostaglandin synthesis can reduce the diuretic action of these agents

LOOP DIURETICS

47

Decrease renal vascular resistance and increase renal blood flow

LOOP DIURETICS

48

Other actions of loop diuretics

1. Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance (↑ renal blood flow)
*Prostacyclin – impt role in mediating renin release reponse to loop diuretics
*Prostaglandins have a role in their diuretic action and NSAIDS like indomethacin that interfere in prostaglandin synthesis can reduce the diuretic action of these agents

2. Decrease renal vascular resistance and increase renal blood flow

49

Lasix dosage form

Tablet and ampule

50

– greater S/E therefore limited use (a loop diuretic)

Ethacrynic acid

51

more potent than furosemide , ↑ use

Bumetanide

52

DOC: acute pulmonary edema of HF

LOOP diuretics
given parenterally due to rapid action

53

Ind: Hypercalcemia (+hydration)

LOOP DIURETICS

54

Ind: - Hyperkalemia

LOOP DIURETICS

55

Ind: Hyponatremia
(+ hypertonic saline

LOOP DIURETICS

56

Ind: Acute renal failure
(oliguric to nonoliguric)

LOOP DIURETICS

57

Ind: - Forced diuresis in drug overdose

LOOP DIURETICS

58

Ind: Hypertension refractory to other diuretics or antihypertensives

LOOP DIURETICS

59

Administered orally or parenterally

LOOP DIURETICS

60

rapid onset of action (IV)

LOOP DIURETICS

61

duration of action is relatively brief (2 to 4 hrs)

LOOP DIURETICS

62

secreted into urine

LOOP DIURETICS

63

A/E Hypokalemia
TX?

Tx: Potassium-sparing diuretics or dietary supplementation with K+
LOOP DIURETICS

64

A/E Hypomagnesemia

(chronic use + low dietary intake of Mg 2+) = Elderly
LOOP DIURETICS

65

A/E Hyperuricemia

furosemide, ethacrynic acid compete with uric acid for the renal and biliary secretory systems, thus blocking its secretion and inturen causing or exacerbating gouty attacks)
LOOP DIURETICS

66

A/E Ototoxicity

(+aminoglycosides; rapid IV > PO)
*Tinnitus- hearing impairment deafness, vertigo, sense of fullness in the ears
*vestibular function too affected
LOOP DIURETICS

67

A/E - Sulfonamide-related hypersensitivity rxns

(Furosemide and Bumetanide)
LOOP DIURETICS

68

- synthesized to enhance potency of CAIs

Thiazides

69

- discovered to increase NaCl excretion

Thiazides

70

- Benzothiadiazine derivatives (chlorothiazide) are

Thiazides

71

- Most widely used diuretic drugs for tx of Hypertension

Thiazides

72

- Sulfonamide derivatives; related in structure to CAIs

- Significantly greater diuretic activity than acetazolamide
Thiazides

73

- Affect the distal convoluted tubule

Thiazides

74

- All have equal max diuretic effects, differing only in potency(expressed on a per-milligram basis) -> “ceiling diuretics”

*Even if increase dose of drug, it will not give ↑/enhance therapeutic action but only toxic actions
Thiazides

75

Act mainly in the cortical region of the ascending loop of Henle and the distal tubule to decrease the reabsorption of Na+, apparently by inhibition of a Na+/Cl- co-transporter on the luminal membrane of the tubules

Thiazides

76

- first modern diuretic that was active orally and was capable of affecting the severe edema of cirrhosis and heart failure w/ a min. of S/E




Chlorothiazide

77

- less ability to inhibit CA than chlorothiazide

Hydrochlorothiazide

78

- Newer derivative used more commonly

Hydrochlorothiazide

79

- more potent (required dose is considerably lower)

Hydrochlorothiazide

80

- efficacy is exactly the same as that of the parent drug

Hydrochlorothiazide

81

IND: - mainstay of antihypertensive medication

Thiazides

82

IND:- HF (when additional diuresis is needed)

Thiazides

83

IND:- Hypercalciuria

Thiazides

84

IND:- Nephrogenic diabetes insipidus (substitute for ADH)

Thiazides

85

- Effective orally

Thiazides

86

- Most thiazides take ___ wks to produce a stable reduction in BP

1 to 3 wks

87

- Exhibit a prolonged biologic half-life

Thiazides

88

- secreted by the organic acid secretory system of the kidney

Thiazides

89

A/E - Hypokalemia (↑common)

Thiazides

90

A/E - Hyponatremia

Thiazides

91

A/E - Hyperuricemia

- increase serum uric acid by decreasing the amt of acid excreted by the organic acid secretory system
Thiazides

92

A/E - Hypercalcemia

Thiazides

93

A/E - Hyperglycemia

- due to impaired release of inculin and tissue uptake of glucose
Thiazides

94

A/E - Hyperlipidemia

Thiazides

95

A/E - Volume depletion

Thiazides

96

A/E - Hypersensitivity rxns

Thiazides

97

- compounds that lack the thiazide structure but like thiazides they have the unsubstituted sulfonamide groups and share same MOA

Thiazide -like

98

- Non-thiazide derivatives that behaves like HCTZ

Chlorthalidone

99

- very long duration of action ; therefore, is often used to tx Hypertension

Chlorthalidone

100

- given 1/d for this in

Chlorthalidone

101

- more potent than thiazides

Metolazone

102

- causes Na+ excretion in advanced renal failure

Metolazone

103

- lipid-soluble, nonthiazide diuretic that has a long duration of action

Indapamide

104

- at low doses, shows significant antihypertensive action w/ min diuretic effects

Indapamide

105

- metabolized and excreted by the GIT and kidneys

Indapamide

106

- less likely to accumulate in patients w/ renal failure

Indapamide

107

- act in the collecting tubule to inhibit Na reabsorption and K+ excretion

Potassium-sparing diuretics/ Na-channel inhibitors

108

- Major use: Tx of hypertension, most often in combination w/ a thiazide

Potassium-sparing diuretics/ Na-channel inhibitors

109

- discontinue exogenous K supplementation

Potassium-sparing diuretics/ Na-channel inhibitors

110

- close monitory of serum K levels

Potassium-sparing diuretics/ Na-channel inhibitors

111

- avoided in patients with renal dysfunction because of increased risk of hyperkalemia

Potassium-sparing diuretics/ Na-channel inhibitors

112

- synthetic steroid that antagonizes aldosterone at intracellular cytoplasmic receptor sites

Spironolactone

113

- Inactive spironolactone-receptor complex (does not bind to DNA -> inhibition of protein synthesis)

Spironolactone

114

- mediator proteins not present to stimulate Na+/K+ exchange sites

Spironolactone

115

- Inhibition of Na+ reabsorption and K+/H+ secretion

Spironolactone

116

*in patients with no significant circulating levels of aldosterones, like with Addison disease (primary adrenal deficiency) , no diuretic effect of the drug occur

Spironolactone

117

(Spironolactone + HCTZ)

ALDAZIDE

118

- often given in conjunction w/ a thiazide or loop diuretic to prevent the K+ excretion

Aldosterone Antagonist

119

- diuretic of choice in patients with hepatic cirrhosis

Aldosterone Antagonist

120

- secondary hyperaldosteronism

Aldosterone Antagonist

121

- completely absorbed orally

Aldosterone Antagonist

122

- strongly bound to proteins

Aldosterone Antagonist

123

- rapidly converted to an active metabolite, canrenone (has mineralocorticoid-blocking activity)

Aldosterone Antagonist

124

- induces hepatic cytochrome P450

Aldosterone Antagonist

125

- Gastric upsets -> peptic ulcers

Aldosterone Antagonist

126

- Gynecomastia in male patients; menstrual irregularities in female patients (high doses on chronic use)

Aldosterone Antagonist

127

- Hyperkalemia, nausea, lethargy and mental confusion

Aldosterone Antagonist

128

- block Na+ transport channels, resulting in a decrease in Na+/K+ exchange

Triamterene and Amiloride

129

- ability to block the Na+/K+ - exchange site does not depend on the presence of aldosterone

Triamterene and Amiloride

130

- not very efficacious diuretics

Triamterene and Amiloride

131

- commonly used in combination with other diuretics usually for their potassium-sparing properties

Triamterene and Amiloride

132

- leg cramps

Triamterene and Amiloride

133

- possibility of increased blood urea nitrogen, uric acid and K+ retention

Triamterene and Amiloride

134

- agents that are freely filtered at the glomerulus, undergo limited reabsorption by the renal tubule, and are relatively inert pharmacologically

Osmotic diuretics

135

- administered in large enough doses to increase significantly osmolality of plasma and tubular fluid

Osmotic diuretics

136

- not useful for treating conditions in which Na retention occurs

Osmotic diuretics

137

Increase the osmotic pressure at the PCT and LOH to prevent water reabsorption

Osmotic diuretics

138

what about mannitol?

- IV only
- prolonged standing of mannitol (may ppt)
- subject to heat (glass bottles); shake bottles (agitate) until clear

139

- used to maintain urine flow following acute toxic ingestion of substances capable of producing acute renal failure

Osmotic diuretics

140

- mainstay treatment for patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities and trauma

Osmotic diuretics

141

- extracellular water expansion

Osmotic diuretics

142

- dehydration

Osmotic diuretics

143

- hypo- or hypernatremia

Osmotic diuretics

144

*The expansion of extracellular water results because the presence of mannitol in the extracellular fluid extracts water from the cells and causes hyponatremia until diuresis occurs.

Osmotic diuretics