Module 04: Diuretics (Part 02) Flashcards
1
Q
What are the three (3) types of diuretics?
A
(A) Loop Diuretics
(B) Thiazide
(C) Potassium-sparing
2
Q
This inhibit the sodium-potassium-chloride co-transporter (NKCC2) in the thick ascending limb of the loop of Henle, preventing sodium reabsorption and causing significant diuresis.
A
Loop Diuretics
3
Q
Where do loop diuretics act in the kidney?
A
They act on the thick ascending limb (TAL) of the loop of Henle.
4
Q
Why are loop diuretics considered the most effective diuretics?
A
Because the thick ascending limb has a high capacity for sodium reabsorption (~25%), so inhibiting this site leads to significant increase in the distal tubular concentration of sodium, reduced hypertonicity of the surrounding interstitium, and less water reabsorption in the collecting duct.
5
Q
What is a non-sulfonamide loop diuretic?
A
Al loop diuretics are sulfonamides except ethacrynic acid (monosulfonamyl loop or high ceiling diuretic)
6
Q
This is a non-sulfonamide loop diuretic, often used as an alternative for patients allergic to sulfonamide-based diuretics like furosemide, bumetanide, or torsemide.
A
Ethacrynic acid
7
Q
In what conditions are loop diuretics commonly used?
A
They are primarily used to treat edema (due to heart failure, liver cirrhosis, or renal disease) and sometimes hypertension.
8
Q
How do loop diuretics treat edema and hypertension?
A
By inhibiting sodium reabsorption through the NKCC2 co-transporter (Nat, -K+, -Cl co-transporter; 1:1:2 ratio) in the Thick Ascending Limb (TAL) of the Loop of Henle, leading to significant diuresis.
9
Q
Loop diuretics are the most effective diuretic class because:
A
Their site of action has a high capacity for sodium reabsorption.
10
Q
How does renal function affect the efficacy of loop diuretics?
A
The efficacy of loop diuretics is inversely related to renal function— they are less effective in patients with impaired kidney function, such as those with heart failure.
11
Q
This includes peripheral, generalized edema, ascites, and pulmonary edema, often due to renal disease, hepatic disease (cirrhosis), or heart failure (used for symptom relief but no mortality benefit).
A
Edema
12
Q
Edema includes what:
A
(A) Peripheral and generalized edema
(B) Ascites
(C) Pulmonary edema
13
Q
Pulmonary edema usually results from what?
A
From renal disease (including nephrotic syndrome), hepatic disease/cirrhosis and heart failure (used for symptomatic management but no mortality benefit)
14
Q
This especially in heart failure with fluid overload, usually in combination with other agents (not a first-line therapy).
A
Hypertension
15
Q
Explain the relationship between hypertension and loop diuretics.
A
Not first line agent, typically used in combination with other agents.
16
Q
When are loop diuretics contraindicated?
A
(A) Renal insufficiency with increased creatinine or anuria.
(B) Allergy to sulfa drugs (except for ethacrynic acid).
(C) Severe electrolyte imbalance or depletion.
(D) Hepatic coma.
17
Q
What are the available oral tablet doses for furosemide?
A
20 mg, 40 mg, and 80 mg.
18
Q
What is the dose for furosemide injectable solutions?
A
10 mg/mL.
19
Q
What are the available doses for furosemide oral solutions?
A
8 mg/mL or 10 mg/mL.
20
Q
What are the available oral tablet doses for torsemide?
A
5 mg, 10 mg, 20 mg, and 100 mg.
21
Q
What is the dose for torsemide injectable solutions?
A
10 mg/mL.
22
Q
What are the available oral tablet doses for bumetanide?
A
0.5 mg, 1 mg, and 2 mg.
23
Q
What is the dose for bumetanide IV solution?
A
0.25 mg/mL.
24
Q
What is the dose for ethacrynic acid oral tablets?
A
25 mg.
25
What is the dose for ethacrynic acid powder for injection?
50mg
26
How does the absorption of loop diuretics vary among agents?
Absorption varies, with an onset of action typically between 30 to 60 minutes.
27
How does the route of administration affect the absorption of loop diuretics?
Oral administration has a slower onset, while intravenous administration has a faster onset.
28
Which loop diuretics have higher bioavailability, and what are the percentages?
(A) Bumetanide and torsemide: 80%
(B) Furosemide: 50%
29
Which loop diuretic has the longest duration of action and is effective in patients with hepatic dysfunction or heart failure?
Torsemide
30
How are loop diuretics distributed in the body?
They are highly protein-bound, meaning they undergo no renal filtration.
31
How are bumetanide and torsemide metabolized?
They are mostly inactivated in the liver by cytochrome P450 (CYP450).
32
How is furosemide metabolized?
Furosemide undergoes minimal hepatic metabolism.
33
How are loop diuretics primarily excreted?
They are mostly excreted renally (proximal tubule) as unchanged drugs.
34
What is the half-life of furosemide?
1.5 to 2 hours.
35
What is the half-life of bumetanide?
1 hour.
36
What is the half-life of torsemide?
3 to 4 hours.
37
What is the primary mechanism of action (MOA) of loop diuretics?
They block the NKCC2 cotransporter, leading to the excretion of Na+, K+, and Cl-.
38
How do loop diuretics affect urine production?
They increase diuresis, which leads to increased urine output.
39
What is the effect of loop diuretics on blood volume and cardiac preload?
They decrease blood volume, which reduces cardiac preload.
40
How do loop diuretics improve edema?
They promote fluid removal from the body, which reduces edema.
41
What is the effect of loop diuretics on the kidney's ability to dilute or concentrate urine?
They inhibit the kidney's ability to dilute or concentrate urine.
42
Which electrolytes are increased in excretion due to loop diuretics?
Calcium (Ca2+) and Magnesium (Mg2+).
43
What are the significant risks associated with the use of loop diuretics?
Risk of hypomagnesemia, hypocalcemia, and nephrolithiasis.
44
What are the significant adverse effects and toxicity of loop diuretics?
(A) nephrotoxicity
(B) ototoxicity
(C) Fluid and electrolyte loss leading to:
(1) cardiac dysrhythmia (2) orthostatic hypotension
(3) dehydration
(4) dizziness, vertigo, syncope * headaches
(5) GI symptoms (abdominal cramps, nausea, constipation, diarrhea)
(6) muscle cramps
(7) metabolic alkalosis, prerenal azotemia
(D) skin photosensitivity
45
What is an important daily task for monitoring patients on loop diuretics?
(1) Monitor daily weight and intake/output (I/O).
(2) Perform serial blood pressure checks.
46
What should be monitored for when administering loop diuretics regarding electrolytes and fluid balance?
Monitor for electrolyte, fluid, and acid-base abnormalities.
47
Name medications that, when administered with loop diuretics, increase the risk of hypokalemia.
Corticosteroids, antipsychotic drugs, and Amphotericin B.
48
Which medications increase the risk of nephron- and/or ototoxicity when given with loop diuretics?
Aminoglycosides and Probenecid.
49
Why should loop diuretics be used cautiously in patients with hyperuricemia or gout?
Loop diuretics may precipitate or aggravate gout.
50
What autoimmune disease requires caution when prescribing loop diuretics?
Systemic Lupus Erythematosus (SLE).
51
What conditions related to kidney or liver function require special precautions when using loop diuretics?
Renal insufficiency and kidney or liver disease.
52
How can loop diuretics affect patients with QT prolongation?
Diuretic-induced hypokalemia may worsen QT prolongation.
53
What interaction between digoxin and loop diuretics increases the risk of cardiac arrhythmias?
The digoxin-diuretic interaction can increase electrolyte imbalances, leading to cardiac arrhythmias.
54
How does hypokalemia caused by loop diuretics affect digoxin therapy?
Hypokalemia increases the risk of digoxin toxicity.
55
What risk should be monitored in diabetic patients taking loop diuretics?
They are at risk of hyperglycemia, requiring periodic monitoring of blood glucose levels.
56
What should be considered when prescribing loop diuretics during pregnancy and lactation?
Loop diuretics are Pregnancy Category C, so use with caution.
57
These drugs inhibit the sodium-chloride (Na/Cl) transporter in the distal convoluted tubule (DCT).
Thiazide diuretics
58
How do thiazide diuretics compare to loop diuretics in terms of diuresis and natriuresis?
Thiazide diuretics are less efficacious than loop diuretics because the Na/Cl transporter reabsorbs only about 5% of filtered sodium.
59
Which part of the kidney do thiazide diuretics primarily act on?
The proximal segment of the distal convoluted tubule (DCT).
60
What happens to sodium levels when the Na/Cl channel is blocked by thiazide diuretics?
Decreased sodium crosses the luminal membrane, reducing the action of the sodium-potassium (Na/K) pump.
61
How does the blockage of the Na/Cl channel by thiazide diuretics affect water movement?
It decreases the passage of sodium and water to the interstitium, leading to increased excretion.
62
How do both loop and thiazide diuretics affect sodium delivery in the kidney?
They increase sodium delivery to the distal segment of the distal convoluted tubule (DCT).
63
Why does increased sodium in the distal tubule cause potassium loss?
It stimulates the aldosterone-sensitive sodium pump, increasing sodium reabsorption in exchange for potassium and hydrogen ions, which are excreted into the urine.
64
What hormonal system is activated due to the reduced blood volume caused by loop and thiazide diuretics?
The renin-angiotensin-aldosterone system (RAAS) is activated.
65
How does increased aldosterone affect potassium and hydrogen ions when using loop or thiazide diuretics?
It increases potassium and hydrogen ion excretion into the urine.
66
What is the combined result of sodium reabsorption and potassium/hydrogen ion excretion in the context of thiazide and loop diuretic use?
The diuretics lead to potassium and hydrogen ion loss, contributing to potential hypokalemia and metabolic alkalosis.
67
Thiazide diuretics are used as adjunctive therapy for edema in which conditions?
Heart failure and hepatic cirrhosis resulting in ascites.
67
What is one of the primary indications for thiazide diuretics?
Hypertension
68
Can thiazide diuretics be used in patients with mild to moderate renal dysfunction?
Yes, they are indicated for mild to moderate renal dysfunction (CKD stages 1-3), including nephrotic syndrome, glomerulonephritis, and chronic renal failure.
69
In which stage of chronic kidney disease (CKD) are thiazide diuretics relatively contraindicated?
Thiazides are relatively contraindicated in CKD stages 4 and 5, especially in patients with anuria or severe renal failure.
70
Thiazide diuretics are used in patients undergoing which types of therapies that can cause fluid retention?
Corticosteroid use and estrogen therapy.
71
What is the usual dose of HCTZ for edema management?
25 mg to 100 mg orally once or twice daily.
71
How can HCTZ be administered to minimize the risk of excessive response or electrolyte imbalance in edema patients?
Some patients may respond to intermittent therapy, such as administering on alternate days or 3 to 5 days per week.
72
What is the initial dose of HCTZ for treating hypertension?
25 mg orally once daily.
73
What is the maintenance dose of HCTZ for hypertension?
The maintenance dose can be increased to 50 mg orally daily, as a single or divided dose.
74
When treating hypertension with HCTZ in combination with other antihypertensive agents, what is the typical maximum dose required?
Patients usually do not require doses in excess of 50 mg daily.
75
How is HCTZ metabolized in the body?
HCTZ is not metabolized.
76
How is HCTZ excreted from the body?
It is eliminated in the urine in its unchanged form.
77
What is the half-life of HCTZ in patients with normal renal function?
The half-life ranges from 5.6 to 14.8 hours, with an average of 10 hours.
78
How does renal failure affect the half-life of HCTZ?
The half-life is prolonged in renal failure because the drug is primarily eliminated via the kidneys.
79
What is the primary mechanism of action (MOA) of thiazide diuretics?
They inhibit the sodium-chloride (Na+/Cl−) co-transporter in the distal convoluted tubule (DCT), reducing Na+ reabsorption.
80
How does blocking the Na+/Cl− co-transporter in the DCT result in diuresis?
Water follows sodium, and with less Na+ reabsorbed, water stays in the tubules, leading to diuresis.
81
What effect do thiazide diuretics have on plasma volume and blood pressure (BP)?
Diuresis leads to decreased plasma volume and lowered BP.
82
How does thiazide diuretic use initially affect the renin-angiotensin-aldosterone system (RAAS) and sympathetic tone?
There is a transient increase in RAAS and sympathetic tone to compensate for the drop in BP and cardiac output.
83
Why is there a synergistic effect between thiazides and ACE inhibitors (ACEis) or angiotensin receptor blockers (ARBs)?
The transient increase in RAAS caused by thiazides is counteracted by ACEis/ARBs, enhancing the blood pressure-lowering effect.
84
How do thiazide diuretics affect vasodilation?
They cause modest vasodilation, though the exact mechanism is unclear.
85
Which electrolytes are increased in excretion due to thiazide diuretics?
Sodium (Na+), chloride (Cl−), potassium (K+), and water.
86
What is the effect of thiazide diuretics on calcium (Ca2+) reabsorption?
Thiazides increase calcium reabsorption.
87
How does reduced sodium excretion lead to increased calcium reabsorption in the DCT?
Lower intracellular Na+ levels trigger a compensatory exchange of Na+ for Ca2+ via the basolateral Na+/Ca2+ exchanger, increasing calcium reabsorption.
88
How do Thiazide Diuretics affect sodium reabsorption?
Thiazide diuretics decrease Na⁺ reabsorption in the DCT, leading to increased sodium delivery to the collecting ducts (CDs).
88
Thiazide Diuretics - Primary Action Site
Thiazide diuretics inhibit sodium (Na⁺) reabsorption in the distal convoluted tubule (DCT) of the nephron.
89
What is the consequence of increased sodium delivery to the collecting ducts (CDs)?
Increased Na⁺ in the collecting ducts stimulates aldosterone release, which then acts on the sodium-potassium (Na⁺/K⁺) exchanger.
90
How does aldosterone contribute to hypokalemia in thiazide diuretic use?
Aldosterone stimulates the Na⁺/K⁺ exchanger, causing increased Na⁺ reabsorption and increased K⁺ excretion, leading to hypokalemia.
91
What is the connection between thiazide diuretics and metabolic alkalosis?
Thiazides increase K⁺ excretion in the collecting ducts, stimulating the K⁺/H⁺ exchanger, which reabsorbs K⁺ in exchange for H⁺. This loss of H⁺ leads to metabolic alkalosis.
92
How does the K⁺/H⁺ exchanger contribute to metabolic alkalosis?
In the collecting ducts, the K⁺/H⁺ exchanger reabsorbs K⁺ while excreting H⁺, reducing the amount of H⁺ in the blood, contributing to metabolic alkalosis.
93
What are the significant adverse effects and toxicity of thiazide diuretics?
Adverse effects of thiazide diuretics stem from the ionic imbalance caused due to the initial Na loss in the DCT.
(A) Hypokalemia
(B) Hyponatremia
(C) Metabolic alkalosis
(D) Hypercalcemia
(E) Hyperglycemia
(F) Hyperuricemia
(G) Hyperlipidemia
94
The mechanism of this in patients using thiazide diuretics is unclear, but it is thought to be an acute response to high-dose thiazide treatment.
Hyperlipidemia
95
What is the common observation regarding lipid levels during thiazide diuretic treatment?
Thiazide diuretics, particularly at high doses, may cause increased lipid levels (hyperlipidemia), although the exact mechanism remains unknown.
96
Why are sulfonamide allergies relevant to thiazide diuretic use?
Thiazide diuretics are sulfa-containing drugs. Patients with sulfonamide allergies may have adverse reactions, including rash, swelling, wheezing, and more severe reactions like anaphylaxis.
97
What symptoms might indicate a sulfonamide allergy in a patient taking thiazides?
Symptoms can include headaches, rash, hives, swelling of the mouth and lips, wheezing or trouble breathing, asthma attacks, and anaphylaxis.
98
What is a key nursing responsibility when monitoring patients on thiazide diuretics?
Monitor daily weight to assess fluid status and detect signs of fluid retention or dehydration.
99
What lab values are key when using thiazide diuretics?
Blood pressure, creatinine, Na⁺, and K⁺ levels.
100
Which diuretics are stronger and longer-lasting than HCTZ?
Chlorthalidone and Indapamide are 1.5-2x stronger and have a longer half-life.
101
What did the ALLHAT trial show about thiazide diuretics?
ALLHAT showed thiazides reduce cardiovascular events and have the most evidence supporting their use.
102
What common side effect is associated with thiazide use?
Hypokalemia (low K⁺).
103
This is known as the first-line agent for hypertension, though less effective than chlorthalidone or indapamide.
Hydrochlorothiazide (HCTZ)
104
In what combination is HCTZ often found?
Combined with ACE inhibitors (ACEIs), ARBs, or calcium-channel blockers.
105
At what creatinine clearance (CrCl) is HCTZ less effective?
HCTZ is less effective when CrCl < 30 ml/min.
106
This drug is characterized to be more effective than other thiazides at CrCl < 30 ml/min and often combined with other diuretics.
Metolazone
107
Which medical conditions require caution when using thiazide diuretics?
Diabetes, hypercalcemia, and hepatic impairment.
108
Which medications can interact with thiazide diuretics?
Lithium, carbamazepine, corticosteroids, and NSAIDs.
109
Are thiazide diuretics safe during pregnancy and lactation?
Thiazides are Pregnancy Category C, caution is advised during pregnancy and lactation.
110
They spare potassium (K⁺) and do not act directly on sodium transport.
Potassium-sparing diuretics
111
What are the two main types of potassium-sparing diuretics?
(A) Aldosterone receptor antagonists (Spironolactone, Eplerenone)
(B) Sodium channel blockers (Amiloride).
112
Where do potassium-sparing diuretics act in the nephron?
Collecting duct, reducing Na⁺ reabsorption and increasing urine output.
113
What are the primary indications for potassium-sparing diuretics?
Edema due to Conn syndrome or ectopic ACTH production (primary mineralocorticoid excess).
114
What conditions cause secondary mineralocorticoid excess, treatable with K⁺-sparing diuretics?
Edema due to states of depleted intravascular volume resulting in secondary mineralocorticoid excess:
(A) Heart failure/post-MI (especially eplerenone)
(B) Cirrhosis
(C) Nephrotic syndrome
(D) Resistant hypertension (typically ni addition to 1st-line antihypertensive agents)
115
Which potassium-sparing diuretic is especially used post-MI or for heart failure?
Eplerenone is often used post-MI and in heart failure.
116
What are the contraindications of potassium sparing diuretics?
(A) Hypersensitivity
(B) Hyperkalemia
(C) Addison disease/adrenal insufficiency
(D) Anuria or severe and progressive CKD
(E) Severe hepatic disease
(F) Pregnancy (Pregnancy Category D)
(especially the aldosterone antagonists, may cause feminization of a male fetus)
117
What is the oral dose of K⁺-sparing diuretics for edema or hypertension?
25 - 200 mg/day, given once or twice daily.
118
What is the recommended dose for congestive heart failure?
12.5 - 25 mg/day, with a maximum of 50 mg/day.
119
What is the dose for treating hypokalemia, and what must be avoided?
25 - 200 mg/day, and potassium supplements must NOT be used.
120
What is the peak activity time for spironolactone?
Peak activity occurs in 2-4 hours.
121
How is spironolactone absorbed in the body?
Well absorbed in the gastrointestinal tract (GIT); bioavailability reaches 95.4% when taken with food.
122
What is the maximum concentration time for spironolactone and its active metabolite?
Spironolactone reaches maximum concentration in 2.6 hours; Canrenone reaches it in 43 hours.
123
What is the protein binding percentage of spironolactone?
Over 90% protein-bound in plasma; Canrenone can be up to 98%.
124
Does spironolactone cross the placental barrier?
Yes, it crosses the placental barrier.
125
What are aldosterone antagonists also known as?
They are also called mineralocorticoid receptor antagonists (MRAs).
126
What is the mechanism of action (MOA) of aldosterone antagonists like spironolactone and eplerenone?
They bind to basolateral mineralocorticoid receptors in the collecting duct, acting as competitive antagonists to aldosterone.
127
What effects does aldosterone have in the kidneys?
Aldosterone stimulates:
(A) Na⁺/K⁺-ATPase production (Na⁺ reabsorption)
(B) ENaC for Na⁺ reabsorption
(C) ROMK for K⁺ excretion.
128
How does aldosterone affect water retention?
Increases Na⁺ reabsorption, leading to water retention due to osmotic forces.
129
What are the common fluid and electrolyte abnormalities associated with K⁺-sparing diuretics?
(A) Hyperkalemia
(B) Hyperchloremic metabolic acidosis
(C) Hyponatremia
(D) Hypomagnesemia
(E) Hypocalcemia
(F) Hypovolemia
129
What are the results of aldosterone antagonism?
(A) Increased Na⁺ reabsorption → causes diuresis (water remains in the tubular lumen).
(B) Increased K⁺ excretion → results in potassium-sparing.
(C) Increased H⁺ excretion → leads to a trend toward metabolic acidosis.
130
What symptoms may arise from the use of potassium-sparing diuretics?
(A) Dizziness and headache
(B) Muscle cramps
(C) Gastrointestinal distress: abdominal cramping, nausea, vomiting, diarrhea
(D) Photosensitivity (specifically with triamterene)
131
What additional effects are specific to spironolactone due to its antiandrogenic properties?
(A) Gynecomastia
(B) Impotence and decreased libido
(C) Menstrual abnormalities
132
What should be monitored daily in patients on potassium-sparing diuretics?
Daily weight and intake/output (I/O).
133
What vital sign should be checked serially?
Blood pressure.
134
Which electrolytes and lab values should be monitored?
Creatinine, Na⁺, K⁺, Ca²⁺, Mg²⁺, BUN, UA, Glucose, and ABGs.
135
When should potassium-sparing diuretics be administered?
Early morning for once-daily doses; avoid late afternoon/evening doses to prevent sleep interference.
135
What precautions should be taken for patients on potassium-sparing diuretics?
Caution in patients with diabetes, gout, and during lactation.
