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MBBS I CPRS > L45 – Diuretics and ACE Inhibitors > Flashcards

L45 – Diuretics and ACE Inhibitors Flashcards

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1
Q

3 types of diuretics?

A

Loop
Thiazide
Potassium-sparing

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2
Q

Name three common loop diuretics? FEB

A

Furosemide
Ethacrynic acid
Bumetanide

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3
Q

Name 2 common thiazide diuretics? HI

A

Hydrocholorothiazide

Indapamide

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4
Q

Name 3 common potassium sparing diuretics? SEA

A

Spironolactone
Eplerenone
Amiloride

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5
Q

Major effect of diuretics ?

A

Increase fluid excretion, lower blood volume, decrease BP

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6
Q

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

A

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

Non-oedematous: decrease hypertension

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7
Q

Result of excessive diuresis?

A

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

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8
Q

Where do loop diuretics act on the kidney tubule?

A

Thick ascending limb of loop of Henle

@ Na/K/2Cl co-transporter at apical membrane

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9
Q

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

A

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+

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10
Q

How does Loop diuretic help treat oedema during heart failure?

A

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

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11
Q

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

A

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

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12
Q

Is loop diuretics used in treatment of hypertension?

A

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

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13
Q

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

A

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

Cause Metabolic alkalosis, hypokalemia, Hyponatremia, Hypomagnesemia

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14
Q

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

A

Exacerbate cardiac arrhythmia

Reverse by decrease Na intake or K+ supplement

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15
Q

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

A

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

IV drip

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16
Q

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

A

Further compromise cardiac function

Reverse by K+ supplement

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17
Q

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

A

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

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18
Q

Complication of hypomagnesemia caused by loop diuretics on heart?

A

Exacerbate cardiac arrhythmia

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19
Q

Complication of lipid levels caused by loop diuretics?

A

Hyperglycemia

Hyperlipidemia

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20
Q

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

A

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

Most likely with ethacrynic acid

Least likely with oral loop diuretics

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21
Q

What type of allergic reaction can loop diuretics cause?

A

Sulfonamide- related allergic reactions

some loop diuretics and thiazides cause this

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22
Q

3 causes of resistance to loop diuretics?

A

Reduction in renal blood flow

Drug interaction

Increased proximal tubular Na+ reabsorption

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23
Q

Which 2 drugs can counteract loop diuretics?

A

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

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24
Q

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

A

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

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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

MBBS I CPRS (78 decks)

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