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Questions and Answers
Which of the following is an acute complication of Acute Kidney Injury (AKI)?
Which of the following is an acute complication of Acute Kidney Injury (AKI)?
Diuretics increase urine output by enhancing absorption of sodium and water in the nephron.
Diuretics increase urine output by enhancing absorption of sodium and water in the nephron.
False
What is the primary site of action for thiazide diuretics?
What is the primary site of action for thiazide diuretics?
Distal convoluted tubule
______ is the brand name for the loop diuretic furosemide.
______ is the brand name for the loop diuretic furosemide.
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Match the following diuretics with their sites of action:
Match the following diuretics with their sites of action:
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What is the main pharmacologic reason for the high efficacy of loop diuretics?
What is the main pharmacologic reason for the high efficacy of loop diuretics?
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Spironolactone and triamterene can both potentially cause hypokalemia.
Spironolactone and triamterene can both potentially cause hypokalemia.
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What type of reaction can sulfonamide-containing diuretics trigger in sensitive patients?
What type of reaction can sulfonamide-containing diuretics trigger in sensitive patients?
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What is the primary effect of K-sparing diuretics on serum potassium levels?
What is the primary effect of K-sparing diuretics on serum potassium levels?
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Loop diuretics are associated with the risk of hyperkalemia.
Loop diuretics are associated with the risk of hyperkalemia.
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List one common clinical use for loop diuretics.
List one common clinical use for loop diuretics.
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The _____ is used for drug dosing adjustments in acute kidney injury (AKI).
The _____ is used for drug dosing adjustments in acute kidney injury (AKI).
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Match the following findings with the type of Acute Kidney Injury (AKI):
Match the following findings with the type of Acute Kidney Injury (AKI):
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Which of the following drugs is associated with prerenal AKI?
Which of the following drugs is associated with prerenal AKI?
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Name one indication for renal replacement therapy (RRT).
Name one indication for renal replacement therapy (RRT).
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Daily labs should include monitoring serum electrolytes and creatinine in AKI patients.
Daily labs should include monitoring serum electrolytes and creatinine in AKI patients.
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What effect do K-sparing diuretics have on serum potassium levels?
What effect do K-sparing diuretics have on serum potassium levels?
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Loop diuretics are typically used to treat hypertension.
Loop diuretics are typically used to treat hypertension.
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What is the common clinical use for thiazide diuretics?
What is the common clinical use for thiazide diuretics?
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Drugs like NSAIDs can lead to prerenal Acute Kidney Injury (AKI) because they reduce _____ mediated afferent vasodilation.
Drugs like NSAIDs can lead to prerenal Acute Kidney Injury (AKI) because they reduce _____ mediated afferent vasodilation.
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Match the following diuretics with their associated risks:
Match the following diuretics with their associated risks:
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What is a common risk associated with using ACE inhibitors in combination with K-sparing diuretics?
What is a common risk associated with using ACE inhibitors in combination with K-sparing diuretics?
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Monitoring intake and output is essential for managing patients with Acute Kidney Injury (AKI).
Monitoring intake and output is essential for managing patients with Acute Kidney Injury (AKI).
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What is the standard IV dose range for furosemide?
What is the standard IV dose range for furosemide?
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The hallmark of Acute Kidney Injury (AKI) is the decline in _____.
The hallmark of Acute Kidney Injury (AKI) is the decline in _____.
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Name one indication for renal replacement therapy (RRT).
Name one indication for renal replacement therapy (RRT).
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What is a chronic complication of Acute Kidney Injury (AKI)?
What is a chronic complication of Acute Kidney Injury (AKI)?
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Diuretics work by promoting the reabsorption of sodium and water in the nephron.
Diuretics work by promoting the reabsorption of sodium and water in the nephron.
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What is the brand name for spironolactone?
What is the brand name for spironolactone?
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Drug formulations for IV must be sterile and _____.
Drug formulations for IV must be sterile and _____.
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Match the following diuretics with their sites of action:
Match the following diuretics with their sites of action:
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Which electrolyte is commonly increased as a side effect of loop diuretics?
Which electrolyte is commonly increased as a side effect of loop diuretics?
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Thiazide diuretics primarily increase potassium excretion.
Thiazide diuretics primarily increase potassium excretion.
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What is the mechanism of action of loop diuretics at the cellular level?
What is the mechanism of action of loop diuretics at the cellular level?
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Spironolactone acts as an _____ receptor antagonist.
Spironolactone acts as an _____ receptor antagonist.
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Which of the following is a common adverse effect of thiazide diuretics?
Which of the following is a common adverse effect of thiazide diuretics?
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Quale di questi diuretici è un inibitore del carbonico anidrasi?
Quale di questi diuretici è un inibitore del carbonico anidrasi?
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Quale degli seguenti non è un diuretico risparmiatore di potassio?
Quale degli seguenti non è un diuretico risparmiatore di potassio?
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Quale combinazione di farmaci include hydrochlorothiazide?
Quale combinazione di farmaci include hydrochlorothiazide?
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Quale dei seguenti diuretici è conosciuto anche con il nome 'Demadex'?
Quale dei seguenti diuretici è conosciuto anche con il nome 'Demadex'?
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Quale di questi diuretici non è disponibile per via orale (PO)?
Quale di questi diuretici non è disponibile per via orale (PO)?
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Which mechanism does Angiotensin II primarily utilize to increase glomerular capillary hydrostatic pressure?
Which mechanism does Angiotensin II primarily utilize to increase glomerular capillary hydrostatic pressure?
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What is a significant effect of Angiotensin II on systemic hydrostatic pressure?
What is a significant effect of Angiotensin II on systemic hydrostatic pressure?
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Which diuretic is NOT classified as a potassium-sparing diuretic?
Which diuretic is NOT classified as a potassium-sparing diuretic?
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Which statement regarding the osmotic diuretic Mannitol is accurate?
Which statement regarding the osmotic diuretic Mannitol is accurate?
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Which combination product includes hydrochlorothiazide?
Which combination product includes hydrochlorothiazide?
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What is the primary action of thiazide diuretics on plasma electrolytes?
What is the primary action of thiazide diuretics on plasma electrolytes?
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Which of the following diuretics is known for having a similarity in structure to sulfonamides?
Which of the following diuretics is known for having a similarity in structure to sulfonamides?
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How does Angiotensin II indirectly promote vasodilation?
How does Angiotensin II indirectly promote vasodilation?
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Which loop diuretic is also known by the brand name 'Bumex'?
Which loop diuretic is also known by the brand name 'Bumex'?
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Which of the following drugs is primarily used for acute management of conditions leading to fluid overload?
Which of the following drugs is primarily used for acute management of conditions leading to fluid overload?
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What physiological effect occurs when the efferent arteriole constricts?
What physiological effect occurs when the efferent arteriole constricts?
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An increased glomerular filtration rate (GFR) is most likely to result from which of the following mechanisms?
An increased glomerular filtration rate (GFR) is most likely to result from which of the following mechanisms?
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What is a potential consequence of an increased GFR?
What is a potential consequence of an increased GFR?
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How does efferent arteriole constriction primarily affect kidney function?
How does efferent arteriole constriction primarily affect kidney function?
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Which of the following statements best describes the relationship between efferent arteriole constriction and urine output?
Which of the following statements best describes the relationship between efferent arteriole constriction and urine output?
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Study Notes
Acute Kidney Injury (AKI) Complications
- Acute: Fluid overload, electrolyte imbalances (e.g., hyperkalemia), metabolic acidosis, and uremia.
- Chronic: Progression to chronic kidney disease (CKD) and long-term cardiovascular complications.
Diuretics
- Medications increasing urine production by inhibiting sodium and water reabsorption in the nephron.
Generic Names, Classes, and Brand Names
- Furosemide (Loop Diuretic) → Lasix
- Triamterene (K-sparing diuretic) → Dyrenium
IV Drug Formulations
- Common vehicles are Sterile Water for Injection (SWFI) and Normal Saline.
- Bacteriostatic water is used for multidose vials.
IV Drug Formulation Requirements
- Must be sterile
- Must be pyrogen-free
Chemical Basis for IV Drug Incompatibilities
- Precipitation occurs due to pH changes or incompatibility between cations and anions (e.g., calcium and phosphate).
Sulfonamide Allergy from Diuretics
- Diuretics like loop diuretics (except ethacrynic acid) and thiazides contain sulfonamide groups which may trigger allergic reactions.
Sites of Action of Diuretics
- Carbonic Anhydrase Inhibitors: Proximal tubule
- Loop Diuretics: Thick ascending limb of the loop of Henle
- Thiazides: Distal convoluted tubule
- K-sparing diuretics: Collecting duct
Molecular Sites of Action for Diuretics
- Loop Diuretics: Inhibit Na+/K+/2Cl- cotransporter.
- Thiazides: Inhibit the Na+/Cl- symporter in the distal tubule.
Spironolactone vs. Triamterene
- Spironolactone: Aldosterone receptor antagonist.
- Triamterene: Blocks ENaC channels in the collecting duct.
Efficacy vs. Potency of Diuretics
- Efficacy: Maximum diuretic effect.
- Potency: The dose required to produce a specific effect.
Pharmacologic Reason for Efficacy Variation
- Loop diuretics have high efficacy due to their action on the loop of Henle, where a significant portion of sodium reabsorption occurs.
Effects on Serum Concentrations
- Loop Diuretics: ↓ Na+, K+, Ca2+; ↑ Uric acid
- Thiazides: ↓ Na+, K+; ↑ Ca2+
Spironolactone and Aldosterone
- Spironolactone competes with aldosterone, reducing sodium reabsorption and potassium excretion.
Common Adverse Effects of Diuretics
- Hypokalemia with loop/thiazides
- Hyperkalemia with K-sparing diuretics
Effect on Serum Potassium
- Loop and thiazides: Promote potassium loss
- K-sparing diuretics: Retain potassium
Hypokalemia vs. Hyperkalemia Risks
- Hypokalemia: Loop, thiazides.
- Hyperkalemia: Spironolactone, triamterene.
Elimination Profiles of Diuretics
- Loop diuretics: Rapid elimination via kidneys.
- Thiazides: Longer half-lives.
PK/PD of Loop Diuretics
- Furosemide: High-ceiling diuretic with a short duration; requires frequent dosing for a persistent effect.
Common Drug-Drug Interactions
- NSAIDs reduce efficacy by decreasing renal blood flow
- Combination with ACE inhibitors increases hyperkalemia risk.
NSAID- and ACE/ARB-Induced AKI
- NSAIDs: Reduce prostaglandin-mediated afferent vasodilation.
- ACE inhibitors/ARBs: Block efferent arteriole constriction, lowering GFR.
Diuretics and Drug-Drug Interactions
- Loop diuretics with aminoglycosides increase ototoxicity
- K-sparing diuretics with ACE inhibitors increase hyperkalemia risk
Common Clinical Uses for Diuretics
- Loop diuretics: Edema, CHF
- Thiazides: Hypertension
- K-sparing diuretics: Heart failure, cirrhosis
Signs and Symptoms of AKI
- Prerenal AKI: Hypotension, tachycardia
- Intrinsic AKI: Oliguria, proteinuria.
- Postrenal AKI: Flank pain, anuria.
Role of CrCl and GFR in AKI
- GFR decline represents the hallmark of AKI.
- CrCl is used for drug dosing adjustments.
Differentiating AKI Causes
- Prerenal: BUN/Cr ratio > 20:1.
- Intrinsic: Urinalysis reveals casts and protein.
- Postrenal: Imaging reveals obstruction.
Drugs Causing AKI
- Prerenal AKI: NSAIDs, ACE inhibitors.
- Intrinsic AKI: Aminoglycosides.
- Postrenal AKI: Anticholinergics (urinary retention).
Criteria for Renal Replacement Therapy (RRT)
- Indications: Acidosis, electrolyte imbalances, volume overload, and uremia.
Furosemide Dosing
- Standard IV dose: 20–40 mg.
- Brand: Lasix.
Evidence-Based Therapeutic Plan for AKI
- Non-pharmacologic: Fluid management.
- Pharmacologic: Loop diuretics for volume overload.
Rationale for AKI Interventions
- Loop diuretics relieve fluid overload.
- Avoid nephrotoxins to prevent further damage.
Monitoring Parameters for AKI
- Daily Labs: Serum electrolytes, creatinine
- Fluid Balance: Monitor intake/output every shift.
AKI Prevention
- Hydration before contrast media.
- Avoid nephrotoxic drugs in at-risk patients.
Renal Adjustments for AKI Patients
- Use CrCl for dose modifications
- Be cautious with narrow therapeutic index drugs.
Issues in Renally Adjusting Medications
- Timing of drug levels is crucial (e.g., aminoglycosides).
- Adjust doses based on dynamic changes in kidney function.
Acute Kidney Injury (AKI) Complications
- AKI can cause fluid overload, electrolyte imbalances (hyperkalemia), metabolic acidosis, and uremia
- Chronic complications can occur, progressing to CKD and long-term cardiovascular complications
Diuretics
- Diuretics are medications that increase urine production by inhibiting sodium and water reabsorption in the nephron
Diuretic Classes
- Loop Diuretics (e.g., Furosemide [Lasix]) act on the thick ascending limb of the loop of Henle.
- K-sparing Diuretics (e.g., Triamterene [Dyrenium]) act on the collecting duct.
- Thiazides act on the distal convoluted tubule.
- Carbonic Anhydrase Inhibitors act on the proximal tubule.
IV Drug Formulation
- Sterile water for injection (SWFI) and Normal Saline are common vehicles for IV drugs
- Bacteriostatic water is used for multi-dose vials
IV Drug Incompatibilities
- Precipitation can occur due to pH changes or incompatibility between cations and anions (e.g., calcium and phosphate)
Sulfonamide Allergy
- Diuretics, including loop diuretics (except ethacrynic acid) and thiazides, contain sulfonamide groups, which can trigger allergic reactions.
Diuretic Mechanisms of Action
- Loop Diuretics inhibit the Na+/K+/2Cl- cotransporter
- Thiazides inhibit the Na+/Cl- symporter in the distal tubule
- Spironolactone is an aldosterone receptor antagonist, reducing sodium reabsorption and potassium excretion
- Triamterene blocks ENaC channels in the collecting duct
Diuretic Potency and Efficacy
- Efficacy refers to the maximum diuretic effect
- Potency refers to the dose required to achieve a specific effect
- Loop diuretics generally have high efficacy because they act on the loop of Henle, where a significant amount of sodium reabsorption occurs
Diuretic Effects on Serum Concentrations
- Loop Diuretics: ↓ Na+, K+, Ca2+; ↑ Uric acid.
- Thiazides: ↓ Na+, K+; ↑ Ca2+.
Diuretic Adverse Effects
- Hypokalemia (low potassium): Associated with loop and thiazide diuretics
- Hyperkalemia (high potassium): Associated with K-sparing diuretics like spironolactone and triamterene
Diuretic Elimination Profiles
- Loop Diuretics: Rapid elimination via kidneys
- Thiazides: Longer half-lives
Diuretic PK/PD
- Furosemide: High-ceiling diuretic with short duration, requiring frequent dosing for sustained effect
Diuretic Drug-Drug Interactions
- NSAIDs: Reduce diuretic efficacy by decreasing renal blood flow
- ACE Inhibitors: Increase risk of hyperkalemia when combined with K-sparing diuretics
- Aminoglycosides: Increase ototoxicity when combined with loop diuretics.
NSAID and ACE/ARB-Induced AKI
- NSAIDs reduce afferent arteriole vasodilation by inhibiting prostaglandin-mediated effects
- ACE inhibitors/ARBs block efferent arteriole constriction, leading to a decline in GFR.
Diuretic Clinical Uses
- Loop Diuretics: Edema, CHF
- Thiazides: Hypertension
- K-sparing Diuretics: Heart failure, cirrhosis
AKI Signs and Symptoms
- Prerenal AKI: Hypotension, tachycardia
- Intrinsic AKI: Oliguria, proteinuria
- Postrenal AKI: Flank pain, anuria
AKI Monitoring and Diagnosis
- GFR decline is the hallmark of AKI
- CrCl is used to assess kidney function and adjust drug doses.
- BUN/Cr ratio greater than 20:1 suggests prerenal AKI
- Urinalysis showing casts and protein is indicative of intrinsic AKI
- Imaging studies are used to identify postrenal obstruction
AKI Treatment and Prevention
- Non-pharmacologic: Fluid management
- Pharmacologic: Loop diuretics for volume overload
- Prevention: Hydration prior to contrast media, avoiding nephrotoxic drugs in at-risk patients
- Monitoring: Daily labs (electrolytes, creatinine) and fluid balance
Renal Adjustments for AKI Patients
- Adjust drug dosages based on CrCl
- Be cautious with drugs that have a narrow therapeutic index
AKI Renal Adjustment Complications
- Timing of drug levels is crucial (e.g., aminoglycosides)
- Dose adjustments should reflect dynamic changes in kidney function
Carbonic Anhydrase Inhibitors
- Acetazolamide is available for oral or intravenous administration.
Osmotic Diuretics
- Mannitol is administered intravenously.
Loop Diuretics
- Furosemide is available for oral or intravenous administration.
- Torsemide is available for oral or intravenous administration.
- Bumetanide is available for oral or intravenous administration.
- Ethacrynic acid is available for oral or intravenous administration.
Thiazide Diuretics
- Hydrochlorothiazide is available for oral administration but you should remember the brand name.
- Chlorthiazide is available for oral or intravenous administration.
- Chlorthalidone is available for oral administration.
- Indapamide is available for oral administration.
- Metolazone is available for oral administration.
Potassium-Sparing Diuretics
- Spironolactone is available for oral administration and you should remember the brand name.
- Eplerenone is available for oral administration.
- Triamterene is available for oral administration.
- Amiloride is available for oral administration.
Combination Products
- HCTZ and Triamterene are available in combination for oral administration.
General Information about Diuretics
- All diuretics are prescription only.
Diuretics
- Carbonic anhydrase inhibitors include acetazolamide (PO, IV).
- Osmotic diuretics include mannitol (IV).
- Loop diuretics include furosemide (Lasix) (PO, IV)*, torsemide (Demadex) (PO, IV), bumetanide (Bumex) (PO, IV) and ethacrynic acid (Edecrin) (PO, IV).
- Thiazide diuretics include hydrochlorothiazide (HCTZ) (PO)*, chlorthiazide (Diuril) (PO, IV), chlorthalidone (Thalitone) (PO), indapamide (Lozol) (PO), and metolazone (Zaroxolyn) (PO).
- Potassium-sparing diuretics include spironolactone (Aldactone) (PO)*, eplerenone (Inspra) (PO), triamterene (Dyrenium) (PO), and amiloride (Midamor) (PO).
- Combination products include HCTZ + Triamterene (Dyazide, Maxzide) (PO).
- All diuretics are prescription only.
- *Must know brand name in addition to generic name.
Angiotensin II Effects
- Angiotensin II is a potent vasoconstrictor.
- It directly constricts arterioles, particularly the efferent arteriole.
- Constriction increases glomerular capillary hydrostatic pressure to maintain GFR despite reduced renal perfusion during hypovolemia.
- Angiotensin II can indirectly promote prostaglandin synthesis in the kidneys, particularly PGE2 and PGI2.
- These prostaglandins act to vasodilate the afferent arteriole.
- Vasodilation counteracts excessive vasoconstriction and maintains renal perfusion.
- In systemic circulation, Angiotensin II reduces hydrostatic pressure in systemic capillaries, aiding in fluid retention.
- In the glomerulus, efferent arteriole constriction caused by Angiotensin II increases glomerular capillary hydrostatic pressure, supporting filtration.
Acute Kidney Injury (AKI) Complications
- Acute complications of AKI include acute tubular necrosis, hyperkalemia, metabolic acidosis, and volume overload.
Diuretics
- Diuretics increase urine output by inhibiting the reabsorption of sodium and water in the nephron.
Thiazide Diuretics
- Thiazide diuretics primarily act on the distal convoluted tubule, inhibiting the sodium-chloride symporter.
Loop Diuretics
- Loop diuretics are highly effective due to their action on the ascending limb of the loop of Henle, blocking the sodium-potassium-chloride cotransporter.
- Furosemide is the brand name for the loop diuretic furosemide.
- Loop diuretics can cause hypokalemia and hyperkalemia.
- Loop diuretics commonly used for edema, hypertension, and heart failure.
K-Sparing Diuretics
- K-sparing diuretics like spironolactone and triamterene can increase serum potassium levels due to their action on the collecting duct, blocking the sodium-potassium exchange and aldosterone receptors.
Sulfonamide-Containing Diuretics
- Sulfonamide-containing diuretics can trigger allergic reactions in sensitive patients.
Monitoring AKI
- Serum electrolytes and creatinine should be monitored daily in AKI patients.
- The eGFR is used to adjust drug dosages in AKI.
Prerenal AKI
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can lead to prerenal AKI by reducing prostaglandin-mediated afferent vasodilation.
Renal Replacement Therapy (RRT)
- Renal replacement therapy (RRT) is indicated for acute kidney injury (AKI) with life-threatening electrolyte imbalances, severe fluid overload, or uremia.
Other Diuretics
- Carbonic anhydrase inhibitors block the enzyme carbonic anhydrase, reducing bicarbonate reabsorption and increasing urine flow.
- Osmotic diuretics like mannitol increase osmotic pressure in the renal tubules, promoting water excretion.
Adverse Effects of Diuretics
- Hypokalemia is a common side effect of loop diuretics.
- Thiazide diuretics primarily increase potassium excretion, leading to hypokalemia.
Actions of Diuretics
- Loop diuretics inhibit the sodium-potassium-chloride cotransporter, leading to increased sodium and chloride excretion.
- Spironolactone acts as an aldosterone receptor antagonist.
- Thiazide diuretics can cause hypokalemia, hyponatremia, and hyperglycemia.
Angiotensin II
- Angiotensin II primarily utilizes the renin-angiotensin-aldosterone system (RAAS) to increase glomerular capillary hydrostatic pressure.
- Angiotensin II significantly increases systemic hydrostatic pressure and promotes vasoconstriction.
Drug Combinations
- Hydrochlorothiazide is included in combination products like HCTZ/Losartan and HCTZ/Amlodipine.
Other Key Points
- Monitoring intake and output is essential for managing patients with AKI.
- Standard IV dose range for furosemide is 20-80mg.
- The hallmark of AKI is the decline in glomerular filtration rate (GFR).
- Chronic complications of AKI include chronic kidney disease (CKD) and cardiovascular disease.
- IV drug formulations must be sterile and pyrogen-free.
- Efferent arteriole constriction enhances glomerular filtration rate (GFR).
- Bumex is the brand name for bumetanide, a loop diuretic.
- Efferent arteriole constriction causes a decrease in urine output.
- Ace inhibitors can lead to hyperkalemia in combination with K-sparing diuretics.
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Description
This quiz covers key concepts related to acute kidney injury (AKI) complications and diuretics, including their mechanisms, drug formulations, and possible allergies. It is essential for understanding the impact of diuretics in managing fluid overload and electrolyte imbalances. Test your knowledge on these critical pharmacological topics.
