Diuretics Classification Quiz

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Questions and Answers

Which of the following types of diuretics is characterized by agents that directly antagonize mineralocorticoid receptors?

Loop diuretics

Potassium-sparing diuretics (correct)

Thiazide diuretics

Osmotic diuretics

What is the primary mechanism of action of osmotic diuretics like mannitol?

Increase osmolarity of tubular fluid (correct)

Inhibit sodium ion transport channels

Block mineralocorticoid receptors

Decrease renal excretion of salt

Which adverse effect is most commonly associated with loop diuretics?

Hyperkalemia

Dehydration

Hypokalemia (correct)

Hyperglycemia

Which indication is most appropriate for the use of thiazide diuretics?

Hypertension treatment Signup and view all the answers

Which agent is classified as a carbonic anhydrase inhibitor?

Acetazolamide Signup and view all the answers

What is a clinical use of thiazides in hypertension management?

To manage hypertension in patients with glucose intolerance Signup and view all the answers

Which adverse effect is commonly associated with ADH analogs like desmopressin?

Water intoxication due to fluid overload Signup and view all the answers

What is the mechanism of action of triamterene and amiloride?

Inhibits Na+ transport across Na+ channels in the distal convoluted tubule Signup and view all the answers

In which clinical scenario are demeclocycline and lithium carbonate typically used?

Treatment of syndrome of inappropriate ADH secretion (SIADH) Signup and view all the answers

What adverse effect can result from the elevation of potassium levels?

Hyperkalemia Signup and view all the answers

Which receptor type, when stimulated by desmopressin, promotes vasoconstriction?

V1 receptor Signup and view all the answers

What is one advantage of co-administering triamterene or amiloride with thiazide diuretics?

Prevention of hypokalemia Signup and view all the answers

Desmopressin is primarily used in which of the following conditions?

Neurogenic diabetes insipidus Signup and view all the answers

What is the primary clinical use of mannitol?

Acute reduction of intracranial pressure Signup and view all the answers

Which mechanism of action is associated with loop diuretics?

Inhibits Na+/K+/2Cl- co-transporter Signup and view all the answers

Which of the following adverse effects is associated with thiazide diuretics?

Hyperuricemia Signup and view all the answers

What is the effect of acetazolamide on bicarbonate production?

Decreases bicarbonate production Signup and view all the answers

What role does aldosterone play in the nephron?

Promotes sodium reabsorption in the DCT Signup and view all the answers

Loop diuretics can lead to which of the following electrolyte imbalances?

Hypocalcemia Signup and view all the answers

What is the primary action of thiazide diuretics in the distal convoluted tubule?

Inhibit Na+/Cl- co-transporter Signup and view all the answers

In which condition is acetazolamide contraindicated?

Liver cirrhosis Signup and view all the answers

What is a consequence of increased Na+/K+ exchange activity due to aldosterone?

Increased H+ secretion Signup and view all the answers

What is the effect of osmotic diuretics on the volume of urine?

Increase urine volume Signup and view all the answers

How does the action of carbonic anhydrase affect diuretic efficacy of acetazolamide?

Limits diuretic action through bicarbonate depletion Signup and view all the answers

What is the main characteristic of high-ceiling diuretics?

Rapid and potent diuretic action Signup and view all the answers

What is a common therapeutic use for spironolactone?

Management of heart failure Signup and view all the answers

Study Notes

Diuretics

Diuretics are medications used to increase the excretion of salt and water by increasing urine output and decreasing extracellular fluid (ECF) volume.
They induce diuresis in patients.
Diuretics are classified into several categories.

Classification

Osmotic diuretics: Examples include mannitol and inulin.
Carbonic anhydrase inhibitors: Examples include acetazolamide, dorsoloamide, and brinzolamide.
Loop diuretics: Examples include bumetanide, furosemide, torsemide, and ethacrynic acid.
Thiazide and Thiazide-like diuretics: Examples include bendroflumethiazide, benzothiazide, hydrochlorothiazide, chlorthalidone, indapamide, and metolazone.
Potassium-sparing diuretics: These can be further sub-classified into:
- Agents that antagonize mineralocorticoid receptors, e.g., spironolactone and eplerenone.
- Inhibitors of sodium ion transport channels in the luminal epithelial membrane, e.g., triamterene and amiloride.
- Agents that suppress renin or angiotensin II action, e.g., ACE inhibitors like lisinopril, fosinopril, and captopril.
Angiotensin receptor blockers: Examples include losartan, valsartan, and telmisartan.

Transport Mechanisms/Site of Action

Understanding the mechanism of action of diuretics requires knowledge of the physiological function of the nephron and its electrolyte transport mechanisms.
The Bowman's capsule is responsible for filtering the blood.
Urine formation is a process involving ultra-filtration, secretion, and reabsorption of substances within different sections of the nephron.

Proximal Tubule (PCT)

The PCT is responsible for the reabsorption of electrolytes such as sodium bicarbonate (85%) and sodium chloride.
Water reabsorption (60%) in the Proximal Tubules occurs passively to maintain the osmolality of the proximal tubular fluid.
The proximal tubule initiates NaHCO3- reabsorption via a Na+/H+ exchanger within the luminal membrane.
This process allows for a one-for-one exchange of sodium ion with a proton (H+) from inside the cell.
Na+/K+ ATPase in the basolateral membrane of the PCT pumps the reabsorbed sodium ion into the interstitium to maintain low intracellular concentrations. This maintains proper balance.
Carbonic acid is formed from H+ and HCO3- in the lumen.
Na2HCO3 dissociation occurs into carbon dioxide (CO2) and water (H2O) via carbonic anhydrase (CA) activity.

Loop of Henle

The thin limb is involved in water reabsorption via an osmotic gradient within the medullary interstitium.
Osmotic diuretics further drive water excretion in this segment.
The thick limb is impermeable to water but absorbs 35% of sodium and chloride via a Na+/K+/2Cl− transporter.
This transporter is blocked by loop diuretics, inhibiting Cl- ion absorption and increasing excretion of Na+, K+, and Ca2+.
The luminal positive potential created by this transporter drives the reabsorption of divalent cations (Mg2+ and Ca2+) via the paracellular pathway.

Distal Convoluted Tubule (DCT) and Collecting Tubule (CT)

The DCT is responsible for absorbing about 10% of sodium and chloride (NaCl).
It is impermeable to water, causing fluid dilution.
This transporter is blocked by thiazide diuretics, which inhibits sodium reabsorption, but there is no lumen positive potential for calcium and magnesium reabsorption.
The CT acts as the major site for potassium secretion and final determination of urinary sodium concentration (5-10% of sodium & chloride are reabsorbed).
The reabsorption occurs via the Na+/H+ and Na+/K+ exchangers, which are regulated by mineralocorticoids and urinary sodium concentration

RAAS Pathway (Renin-Angiotensin-Aldosterone System)

RAAS is activated by low plasma sodium concentration and sympathetic stimulation.
Renin is secreted from the juxtaglomerular apparatus (JGA).
Renin converts angiotensinogen to angiotensin I, and angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II.
Angiotensin II is a potent vasoconstrictor and stimulates aldosterone release.
Aldosterone increases sodium and water reabsorption in the distal convoluted tubule, stimulating sodium-potassium exchange, and increases hydrogen ion secretion in the proximal tubule.

Pharmacology of Specific Agents

Mannitol: Provides a high intravenous (IV) osmotic diuresis.
- Mechanism: Filtered by glomeruli, retained in proximal tubules, increasing tubular fluid osmolality, decreasing water reabsorption relative to sodium.
- Clinical uses: reduce intracranial pressure (ICP) in head injuries and intraocular pressure (IOP) in glaucoma.
- Adverse effects: dehydration and fluid overload in patients with impaired kidney function.
Acetazolamide: Inhibits carbonic anhydrase, and reduces the production and reabsorption of bicarbonate from the proximal convoluted tubule (PCT).
- Clinical Uses: reduce aqueous humor formation, decreasing intraocular pressure (IOP) and used in the treatment of glaucoma.
- Adverse effects: metabolic acidosis, drowsiness, kidney stone formation, and paresthesia. Contraindicated in patients with liver cirrhosis.
Loop Diuretics: High ceiling diuretics with rapid and potent diuretic effects, mostly used in treating cardiac failure, pulmonary oedema, acute oliguria or acute renal failure, hypertension and hypercalcemia.
- Mechanism: act in the thick ascending limb of the loop of Henle, inhibiting the Na+/K+/2Cl− co-transporter, blocking Cl- absorption in the tubular lumen increasing Na+, K+, and Ca2+ excretion, hence increasing excreted urine volume. -Adverse effects: hyperglycemia, allergic reactions, hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia, and dehydration.
Thiazide diuretics: Act in the distal convoluted tubule inhibiting the Na+/Cl− co-transporter. These reduce calcium excretion in the urine, also act as weak inhibitors of carbonic anhydrase and increase urinary pH.
- Clinical uses: Used in the treatment of kidney stones and hypertension. -Adverse effects: hyperuricemia, acute renal failure, hypokalemic alkalosis, hyperglycemia due to glucose intolerance, and hypercholesterolemia.
Spironolactone: Direct antagonist to aldosterone, inhibiting the synthesis of tubular Na+ channels and Na+/K+ ATPase, involved in Na+, Cl−, and water reabsorption.
- Clinical uses: used in combination with other antihypertensives, can be used as a replacement for thiazides in patients with hypertension, glucose intolerance, hyperuricemia, and hypokalemia. Also used for treating primary aldosteronism.
- Adverse Effects: Diarrhea, nausea, vomiting, headaches, confusion, somnolence, and gynecomastia.
Triamterene & Amiloride: Inhibit sodium transport across sodium channels in the distal convoluted tubule epithelial membrane.
- Clinical Uses: Weak diuretic action, used in combination with other antihypertensives for treating hypertension.
ADH/ADH Antagonist (e.g., Desmopressin, Demeclocycline, Lithium carbonate): Anti-diuretic hormone (ADH) antagonists increase urine output. -Mechanism: Desmopressin stimulates V1 and V2 receptors in blood vessels and the kidneys, increasing water reabsorption. -Clinical uses: treatment of neurogenic diabetes insipidus and nocturnal enuresis. Used as an adjunct in hemophilia treatment. -Adverse effects: vasoconstriction, smooth muscle cramps, water intoxication, and hyponatremia. Demeclocycline and Lithium carbonate block ADH action increasing urine volume. Used in the treatment of syndrome of inappropriate ADH secretion (SIADH).

Conclusion

The presentation highlighted the diverse classes of diuretic agents, their sites of action in the nephron, mechanisms of action, and clinical uses.
A comprehensive understanding of these agents will be beneficial in clinical practice.

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Description

Test your knowledge on diuretics and their classifications with this quiz. Explore various types of diuretics including osmotic, loop, thiazide, and potassium-sparing categories. Understand their mechanisms and examples used in patient care.