L45 – Diuretics and ACE Inhibitors Flashcards Preview

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Flashcards in L45 – Diuretics and ACE Inhibitors Deck (79):
1

3 types of diuretics?

Loop
Thiazide
Potassium-sparing

2

Name three common loop diuretics? FEB

Furosemide
Ethacrynic acid
Bumetanide

3

Name 2 common thiazide diuretics? HI

Hydrocholorothiazide
Indapamide

4

Name 3 common potassium sparing diuretics? SEA


Spironolactone
Eplerenone
Amiloride

5

Major effect of diuretics ?

Increase fluid excretion, lower blood volume, decrease BP

6

Difference in effect of diuretic agents in oedematous and non-oedematous states?

Oedematous: decrease peripheral or pulmonary oedema WITHOUT significant decrease in blood volume

Non-oedematous: decrease hypertension

7

Result of excessive diuresis?

Further compromise the effective arterial blood volume > decrease perfusion to vital organs

8

Where do loop diuretics act on the kidney tubule?

Thick ascending limb of loop of Henle
@ Na/K/2Cl co-transporter at apical membrane

9

Effect on electrolyte and water balance after loop diuretic action on Loop of henle?

Inhibit Na+/K+/2Cl transporter > decrease reabsorbing Na+, K+, Cl- from filtrate > less medullary hypertonicity + decrease reabsorption of Ca, Mg > increase renal excretion of water, Na+, K+ Ca2+, Mg2+, Cl-, H+

10

How does Loop diuretic help treat oedema during heart failure?

Increase Na+ secretion = less retention of salt = less oedema

11

How does Loop diuretic help treat congestive heart failure and pulmonary oedema?

Increase venous capacitance and lower blood volume = less Left Ventricular filling pressure due to less venous return = relieve congestion

12

Is loop diuretics used in treatment of hypertension?

Not really

Limited use due to short half-life > causes post-diuretic Na+ reabsorption > kidney try to maximally absorb Na to compensate for natriuria > cause undesired fluctuations in BP

13

What are the adverse effects of loop diuretics on electrolytes and what complications entail?

Loop diuretics > depletion of H+, K+, Na+, Mg

Cause Metabolic alkalosis, hypokalemia, Hyponatremia, Hypomagnesemia

14

Complication of hypokalemia caused by loop diuretics? How to reverse effect?

Exacerbate cardiac arrhythmia
Reverse by decrease Na intake or K+ supplement

15

Complication of hyponatremia caused by loop diuretics? How to reverse effect?

Cause ECF depletion, hypotension, reduced GFR, hepatic encephalopathy, thromboembolism

IV drip

16

Complication of Metabolic alkalosis caused by loop diuretics? How to reverse effect?

Further compromise cardiac function

Reverse by K+ supplement

17

Apart from electrolyte imbalance cause by loop diuretics, How does loop diuretic cause gout?

Increase diuresis > hypovolemia > increase re-absorption of uric acid and water > gout

18

Complication of hypomagnesemia caused by loop diuretics on heart?

Exacerbate cardiac arrhythmia

19

Complication of lipid levels caused by loop diuretics?

Hyperglycemia
Hyperlipidemia

20

Adverse effect of loop diuretics on ear? which loop diuretic most likely to cause adverse effect? How to alleviate?

Ototoxicity due to inhibition of electrolyte transport in the ear > hearing problem

Most likely with ethacrynic acid

Least likely with oral loop diuretics

21

What type of allergic reaction can loop diuretics cause?

Sulfonamide- related allergic reactions

some loop diuretics and thiazides cause this

22

3 causes of resistance to loop diuretics?

Reduction in renal blood flow

Drug interaction

Increased proximal tubular Na+ reabsorption

23

Which 2 drugs can counteract loop diuretics?

1) Nonsteroidal anti-inflammatory drugs (NSAIDs)

Increases expression of NAK2Cl co-transporter which is blocked by loop diuretics

2) Probenecid

Compete for organic acid transport system in PCT

24

How does reduction in renal blood flow cause resistance to loop diuretics?

low renal blood flow (e.g. renal failure or drug-induced)

Decrease delivery of diuretics to kidneys + accumulation of endogenous organic acids at PCT = decrease active transport of loop diuretics at PCT

25

How can heart failure, nephrotic syndrome or hepatic cirrhosis cause loop diuretics resistance?

Increased proximal tubular Na+ reabsorption (e.g. heart failure > hypotension > increase RAAS activation > increase salt retention)

Lower delivery of Na+ to loop of Henle, site of action for loop diuretics

26

Which part of kidney tubule does Thiazide target?

Distal tubule

Na+/Cl- cotransporter

27

Explain the action of Thiazides on distal tubule and the electrolyte changes (in Ca2+) it causes?

Inhibit the Na+/Cl- co-transporter in DCT

inhibit Na+ & Cl- re-absorption > decrease intracellular Na+ increases Na+ conc. gradient > drive Na+/Ca2+ exchanger > depletion of Ca2+ in cell causes increase reabsorption of Ca2+

28

Compare action of drug on filtrate Ca2+ between loop diuretics and thiazides?

Loop = excrete more Ca2+

Thiazide = reabsorb more Ca2+

29

Loop D. or Thiazide more potent? Why is one chosen over the other to treat oedema?

Loop D. is more potent

Loop D. to treat oedema

Thiazide acts on DCT where most Na+ is already reabsorbed, less control of Na+ levels

30

Compare the net results in excretion between Loop D and thiazide?

Loop D: increase excretion of Mg, Ca, Na, K, Cl, H+, water

Thiazide: increase excretion of water, Na+, Cl-

31

Which diuretic is used most clinically for mild hypertension and list 3 reasons why?

Thiazide

As efficacious as other drugs for mild hypertension but few contraindications

Inexpensive

Longer acting (once daily dose), safe profile, well-tolerated

32

Name one drug that is synergistic with Thiazide?

Calcium channel blockers

33

Explain the effect of thiazide under chronic administration?

Acute = affect renal only

Long-term administration = decrease TPR > direct vasodilation

34

How does thiazide cause hypokalemia?

Inhibit Na+/Cl- co-transporter in DCT > less intracellular Na > causes increase Na+ reabsorption via Na/K exchanger > more K+ exchanged into filtrate > hypokalemia

35

How does thiazide cause gout?

Hypovolemia > increase uric acid and water reabsorption > uric acid accumulate in joints > gout

36

Compare the side effects of thiazide with loop diuretics?

Same but milder, add on Hypercalcemia

Hypokalemia, Hyponatremia, Hypomagnesemia, Hyperuricemia, hyperlipidemia, hyperglycemia, sulfonamid-related allergic reactions

37

Under what circumstances does thiazide cause hypercalcemia?

Rare, doesnt occur if the Ca2+ regulation is fine

occur if patient has other cause e.g. hyperparathyroidism

38

How could thiazide exacerbate diabetes? (think pancreas)

Thiazide > activate ATP-sensitive K+ channels > hyperpolarize pancreatic b-cells > reduce insulin secretion and tissue use of glucose > hyperglycemia

39

How can hyperglycemia caused by diuretics be reversed?

by correcting hypokalemia by K+ supplement

Because thiazide affect K+ channels in b-cells in pancreas to cause reduced insulin secretion

40

Site of action of potassium sparing diuretics?

Collecting tubule

Inhibit epithelial Na+ influx and K+ efflux

inhibit reabsorption of Na+ and decrease secretion of K+ (& H+) > decrease water reabsorption (water follows Na)

41

Explain difference in action between Amiloride vs Spironolactone and eplerenone?

Amiloride = inhibit Na+ channel activity in collecting tubule

Spironolactone, Eplerenone = antagonize aldosterone receptor

42

How does aldosterone lead to change in NaCl reabsorption in collecting tubule?

Aldoesterone > activate epithelial Na+ channels > increase Na+ conductance in luminal membrane > increase activity of Na+?K+ ATPase in basolateral membrane (by increasing synthesis and distribution of channels)

INCREASE reabsorption of NaCl in collecting tubule

43

How do Aldoesterone antagonists inhibit increase in reabsorption in NaCl in collecting tubule?

block collecting tubule epithelial Na+ membrane> cannot be activated by aldosterone > inhibit Na+ reabsorption and K+ excretion

44

Compare diuretic effect of potassium sparing diuretics with the other 2 types?

Most diuretic: Loop D. > Thiazide > Potassium- sparing diuretic

45

Why is potassium- sparing diuretics least diuretic of all diuretics?

Acting on site where most Na+ is already absorbed

46

Is potassium-sparing diuretics used in the treatment of oedema or hypertension?

Not on its own

Used in combo with other diuretics to increase response and decrease K+ secretion

47

Name and explain 2 electrolyte adverse effects of potassium sparing diuretics?

Hyperkalemia > inhibited secretion of K+ into filtrate

Metabolic acidosis > inhibited secretion of H+

48

Which 2 drugs cant be used with potassium-sparing diuretics and why?

intake of ACE inhibitors, angiotensin receptor blockers > decrease renal excretion of K+ > further exacerbate hyperkalemia > exacerbate cardiac arrhythmia

49

Under what condition is K+ sparing diuretics not used?

Renal disease patients

50

Adverse effect of hyperkalemia caused by K+ sparing diuretic is reversed by what?

Thiazide diuretics

51

What sexual changes can K+ sparing diuretics cause?

Spironolactone: causes:

Gynecomastia (breast enlarge)
Impotence
Menstrual irregularities

Spironolactone is antagonist for androgen and progesterone receptors

52

Which 2 combo diuretics therapies are given ?

Loop + thiazide

K+ sparing + Loop or thiazide

53

What precautions is taken with Loop + thiazide combo therapy?

Resultant hemodynamic changes and hypokalemia

54

When is K+sparing + loop/thiazide combo given?

To manage hypokalemia

55

What are the 2 effects of angiotensin II on angiotensin receptors?

1) vasoconstriction on SM (increase sympathetic function)

2) Fluid retention (increase Na+ reabsorption in PCT, increase release of Vp and aldosterone)

56

When are aldosterone antagonists used?

high aldosterone level (e.g.
heart failure, liver cirrhosis, kidney disease)


reduce cardiac remodeling (e.g. fibrosis in heart failure)

57

Compare the diuretics in electrolyte changes (Na, Ca, K, H)

Na+ : all diuretics excrete

K+: Loop and Thiazide excrete, K+ sparing retention

Ca2+ : Loop excrete, Thiazide retention, K+ sparing no effect

H+ : Loop and thiazide excrete, K+ sparing retention

58

What two molecules is converted by angiotensin converting enzyme?

Angiotensin I > II

Bradykinin > inactive metabolite

59

What is the role of Bradykinin?

Vasodilation

60

Which 2 components of RAAS can be blocked?

Angiotensin receptor

ACE

61

Name of 2 drugs to inhibit RAAS?

Angiotensin converting enzyme inhibitor (ACEi)

Angiotensin receptor blocker (ARB)

62

Name 4 common ACEi?

Catopril
Enalapril
Lisinopril
Quinapril

63

Name 2 common ARB?

Losartan
Valsartan

64

Difference of action between ARB and ACEi?

ACEi inhibits formation of angiotensin II

ARB inhibits actions of angiotensin II (selective of AT1 receptor)

65

Explain the effects of ACEi and ARB?

both: decrease fluid retention and OEDEMA

decrease vasoconstriction and lower TPR = treat HYPERTENSION

lower ventricular remodeling = less fibrosis = improve survival (HEART FAILURE)

66

Is ACEi and ARB better than Loop D to treat oedema?

No

Loop D is better for oedema

67

What are very common adverse effects of ACEi / ARB? Why?

Dry cough

Angioedema

More selective to ACE inhibitor due to increased level of BRADYKININ, can switch to ARB

68

What are rarer and more severe adverse effects of ACEi and ARB?

Severe hypotention (in patients with fluid loss)

Acute renal failure

Hyperkalemia (dont use with K+ sparing diuretic, exacerbate retention of K+)

69

Why are ARB and ACEi not used in pregnant patients?

Risk of fetal hypotension, renal failure, malformation

70

List advantages of ARB over ACEi?

More complete blockage of RAAS

Do not affect AT2 receptors which causes vasodilation and bradykinin release

71

How is ARB and ACEi naturally counteracted in body?

Natural angiotensin II feedback mechanism interrupted by ACEi/ARB

Body compensate by increase release of renin from JG cells

Limit effectiveness of ACEi and ARB

72

What drug is used to conteract body's compensation towards ARB and ACEi?

Renin inhibitor

since body naturally boost renin secretion to compensate for the interrupted angiotensin II feedback mechanism

73

Name one renin inhibitor?

Aliskiren

74

compare the action and side effects of renin inhibitors with ARB/ACEi?

pretty much the same action

without dry cough, angioedema, severe hypotension

Same adverse effects on fetus, hyperkalemia and acute renal failure

75

What is aldosterone escape?

inability of ACE inhibitor or ARB to reliably suppress aldosterone release

Alternative mechanisms e.g. ACTH hormone and high K+ can make aldosterone

76

What drug is used for controlling aldosterone escape?

K+ sparing diuretics (spironolactone, eplerenone)

77

How do aldosterone antogonists improve oedema?

Decrease sodium reabsorption from collecting tubule > less oedema

78

What effects do aldosterone antagonist have on baroreceptors and ventricular remodeling?

Lower sympathetic activation and lower parasym. inhibition > decrease baroreceptor dysfunction

Decrease ventricular remodeling

79

Adverse effects of aldosterone antagonists?

Hyperkalemia

Gynecomastia
Impotence
Menstrual irregularities

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