Carbonic Anhydrase Inhibitors & Osmotic Diuretics

Name: Carbonic Anhydrase Inhibitors & Osmotic Diuretics — Renal pharmacology
Creator: LearnDrugs

High-yield Verified · Oct 2026

Two diuretics prized for what they do outside the kidney. Carbonic anhydrase inhibitors act at the proximal tubule and the ciliary body; mannitol works by osmosis alone. Loop, thiazide and potassium-sparing diuretics act further down the nephron and are taught on their Cardiovascular pages.

Nursing view → administration, monitoring and patient teaching

Compare: Diuretics compared by nephron segment — site, electrolytes and acid–base →

Drugs

acetazolamide —

methazolamide —

mannitol Osmitrol

Mechanism

Acetazolamide and methazolamide inhibit carbonic anhydrase, the enzyme that catalyzes the reversible hydration of carbon dioxide and dehydration of carbonic acid. In the kidney this causes loss of bicarbonate, which carries out sodium, water and potassium, alkalinizing the urine and promoting a mild diuresis; in the eye it decreases aqueous humor secretion and lowers intraocular pressure. Mannitol is an osmotic diuretic: it is filtered and poorly reabsorbed, so it raises the osmolarity of the glomerular filtrate, hinders water reabsorption and increases sodium and chloride excretion, and the rise in extracellular osmolarity draws water out of cells, lowering intracranial and intraocular pressure.

How the proximal tubule reclaims bicarbonate

The proximal tubule reabsorbs about 60 to 70% of the filtered load, including sodium, water and bicarbonate. Sodium enters the cell in exchange for H⁺ through the Na⁺–H⁺ exchanger (NHE3). In the lumen, that H⁺ combines with filtered HCO₃⁻ to form carbonic acid, which luminal (brush-border) carbonic anhydrase splits into H₂O and CO₂. CO₂ diffuses into the cell, where cytosolic carbonic anhydrase re-forms carbonic acid, which yields HCO₃⁻ and H⁺. The HCO₃⁻ leaves across the basolateral membrane with Na⁺ through the Na⁺/HCO₃⁻ cotransporter (NBCe1), and the H⁺ is recycled to NHE3.

Almost 80% of filtered bicarbonate is reclaimed this way, so this pathway is central to acid–base balance.

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Filtered bicarbonate is not carried across directly — it is broken down to CO₂ in the lumen and rebuilt inside the cell, and both steps need carbonic anhydrase.

What blocking carbonic anhydrase does — and why the diuresis fades

Acetazolamide interferes noncompetitively with both the luminal and the cellular enzyme, impairing sodium, bicarbonate and water reabsorption. Bicarbonate stays in the lumen and is lost in the urine with sodium, water and potassium: the urine turns alkaline and a diuresis follows.

The effect is weak and self-limiting. The loop of Henle, distal convoluted tubule and ENaC-bearing distal nephron reabsorb much of the extra sodium delivered to them, and tubuloglomerular feedback is activated. Meanwhile serum bicarbonate falls, which removes the substrate for carbonic anhydrase–mediated sodium reabsorption, so acetazolamide becomes less efficient. On the acetazolamide label, increasing the dose does not increase the diuresis, and edema doses are given intermittently so the kidney can recover from the inhibition. Methazolamide’s diuretic effect is weak and transient, and it should not be used as a diuretic.

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Bicarbonaturia lowers serum bicarbonate, and less filtered bicarbonate means less for the drug to act on.

The acid–base fingerprint: hyperchloremic metabolic acidosis

Wasting bicarbonate in the urine (bicarbonaturia) lowers serum HCO₃⁻, and chloride is released into the plasma to replace the lost negative charge. The result is a normal anion gap, hyperchloremic metabolic acidosis — the same picture as a type 2 (proximal) renal tubular acidosis, which CAIs can also cause. More sodium reaching distal sites is reabsorbed in exchange for potassium, so hypokalemia follows.

The acidosis is useful in two settings. At altitude, the body compensates for the metabolic acidosis by hyperventilating, which raises arterial PO₂ and counteracts the hypoxia-induced respiratory alkalosis — the basis of acetazolamide prophylaxis for acute mountain sickness. By the same logic, acetazolamide can be used to reverse metabolic alkalosis.

Outside the kidney: ciliary body and choroid plexus

In the eye, CAIs reduce aqueous humor production by the ciliary epithelium by reducing the production of bicarbonate ions, presumably reducing fluid flow, which lowers intraocular pressure in glaucoma. In the brain, acetazolamide inhibits the enzyme in the choroid plexus and reduces cerebrospinal fluid production, which is why it is used for idiopathic intracranial hypertension. Systemic CAIs are used when intraocular pressure cannot be lowered with topical agents and in acute angle-closure glaucoma, where vomiting may call for the IV route; the topical CAIs dorzolamide and brinzolamide reach the ciliary body through the cornea (nursing Glaucoma Agents page).

Both oral CAIs are sulfonamide derivatives without antibacterial activity, and methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis are strongly associated with HLA-B*5901.

Mannitol: osmotic diuresis without a transporter

Unlike other diuretics, osmotic diuretics do not interfere with electrolyte transporters. Mannitol is filtered by the glomeruli, less than 10% is reabsorbed, and it is not secreted, so it stays in the tubular fluid of the proximal tubule and thick ascending limb, raising its osmolarity and holding water in the lumen. It also washes out the medullary solute gradient, blunting urine concentration — the same kind of osmotic polyuria that excess tubular glucose causes in diabetes.

In the blood, mannitol raises plasma osmolality. Because it does not cross the intact blood–brain barrier, it creates an osmotic gradient that draws water out of the brain and lowers intracranial pressure; it draws water out of the eye the same way. The catch is the sequence: water moves into the plasma before the kidneys excrete it. Overt expansion of the extracellular volume can precipitate pulmonary edema in heart failure, and if the drug cannot be excreted (anuria) the volume stays. Where the blood–brain barrier is already damaged, as in intracranial hemorrhage, frequent doses can cross it and draw water into the brain.

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Mannitol works only while it stays outside the cells, and only leaves if the kidneys can excrete it.

Comparing the drugs

Site, mechanism and acid–base effect

Drug	Site and target	Urine	Blood acid–base and electrolytes	Main uses
Acetazolamide	Proximal tubule: luminal and cellular carbonic anhydrase; also ciliary body, choroid plexus	Alkaline, bicarbonate-rich	Hyperchloremic metabolic acidosis; hypokalemia, hyponatremia	Glaucoma (oral or IV), acute mountain sickness, idiopathic intracranial hypertension, edema and epilepsy (adjunct)
Methazolamide	Carbonic anhydrase (oral); weak, transient diuretic effect	Alkaline	Transient metabolic acidosis; potassium excretion increased at first	Glaucoma only — not used as a diuretic
Mannitol	No transporter: filtered, < 10% reabsorbed, raises tubular osmolarity	Osmotic diuresis with sodium and chloride	Dilutional hyponatremia first, then hypernatremia and dehydration; hypokalemia	Raised intracranial pressure and cerebral edema; raised intraocular pressure (IV only)

Topical carbonic anhydrase inhibitors (dorzolamide, brinzolamide) act on the eye only and are on the nursing Glaucoma Agents page.

Pharmacokinetics at a glance

Drug	Route	Distribution	Elimination	Half-life
Acetazolamide	Oral or IV (IM not recommended)	Avidly bound by carbonic anhydrase, so concentrated in enzyme-rich kidney and red cells	Not metabolized; about 90% excreted in urine by tubular secretion; dialyzable	6–9 h (one review gives 13 h)
Methazolamide	Oral	Plasma, CSF, aqueous humor, red cells; about 55% protein-bound	About 25% unchanged in urine; renal clearance 20–25% of total	About 14 h
Mannitol	IV only (poorly absorbed orally)	Extracellular space; volume about 17 L	Filtered unchanged; about 80% in urine within 3 h; dialyzable	0.5–2.5 h; about 36 h in renal impairment

Label and StatPearls values. Acetazolamide is ineffective in renal insufficiency because it must be secreted into the tubule to act.

Pharmacokinetics

Concentrated where the enzyme is — acetazolamide, methazolamide: CAIs are avidly bound by carbonic anhydrase, so enzyme-rich tissues such as the kidney and red blood cells hold higher concentrations. Methazolamide’s red cell:plasma ratio was 27:1, 16:1 and 10:1 at rising doses. Methazolamide also reaches high concentrations in cerebrospinal fluid, yet it is not an effective anticonvulsant.
Acetazolamide must be secreted to work — acetazolamide: Diuretics bound to albumin are not filtered, so they reach their luminal target by active secretion; acidic diuretics such as acetazolamide use the organic anion transporters of the proximal tubule. Acetazolamide is not metabolized, almost 90% is excreted by tubular secretion, and it is ineffective in renal insufficiency. Despite its red cell distribution and protein binding it is dialyzable, which helps in overdose with renal failure.
Mannitol leaves only through the glomerulus — mannitol: Total clearance is 87–109 mL/min with normal kidney function, and about 80% of a dose is in the urine within 3 hours. In renal impairment the half-life rose to about 36 hours, so mannitol accumulates — and accumulation increases the risk of hypervolemia. Hemodialysis and peritoneal dialysis remove it.
Salicylates and acetazolamide — acetazolamide: Salicylates displace acetazolamide from plasma protein and inhibit its renal clearance, so free acetazolamide rises; toxicity follows from red cell carbonic anhydrase inhibition. Acetazolamide should also not be used to alkalinize the urine after a salicylate overdose, because it may worsen the metabolic acidosis.

Uses & drug choice

Acetazolamide for adjunctive treatment of glaucoma (chronic open-angle and secondary glaucoma, and before surgery in acute angle-closure glaucoma), edema from heart failure or drugs, and centrencephalic epilepsies
Acetazolamide for the prevention or relief of acute mountain sickness in climbers making a rapid ascent
Methazolamide for lowering intraocular pressure in chronic open-angle glaucoma and secondary glaucoma, and before surgery in acute angle-closure glaucoma
Mannitol (IV) for reducing intracranial pressure and treating cerebral edema, and for reducing elevated intraocular pressure

Acute angle-closure glaucoma awaiting surgery, with vomiting → IV acetazolamide, or IV mannitol before surgery

Systemic CAIs are used in acute angle-closure glaucoma, where vomiting may call for the parenteral route, and IV acetazolamide can reach its maximal effect in about 20 minutes; mannitol lowers intraocular pressure by drawing water out of the eye. Long-term CAI use is contraindicated in chronic angle-closure glaucoma, because the angle may close while the pressure is masked.

A climber planning a rapid ascent to high altitude → Acetazolamide prophylaxis, plus gradual ascent where possible

The metabolic acidosis drives compensatory hyperventilation that raises PaO₂ and counteracts hypoxic respiratory alkalosis, and prophylaxis gave fewer and milder symptoms; it does not remove the need for prompt descent if high-altitude pulmonary or cerebral edema develops.

Raised intracranial pressure from cerebral edema → IV mannitol — not in anuria, severe hypovolemia, severe pulmonary congestion or active intracranial bleeding (except during craniotomy)

Mannitol reduces raised ICP rapidly by drawing water out of the brain across an intact blood–brain barrier. Serum osmolarity, the osmol gap, electrolytes, urine output and ICP are monitored, and repeated doses risk rebound and worse edema. Hypertonic saline is also used for high ICP but is not a diuretic.

Idiopathic intracranial hypertension → Acetazolamide

It inhibits carbonic anhydrase in the choroid plexus and reduces cerebrospinal fluid production, lowering intracranial pressure.

Edema in a patient with cirrhosis → Not a carbonic anhydrase inhibitor

Acetazolamide and methazolamide are contraindicated in cirrhosis because they may precipitate hepatic encephalopathy; their diuresis is weak and self-limiting anyway.

Persistent metabolic alkalosis → Acetazolamide (off-label)

By wasting bicarbonate in the urine, acetazolamide lowers serum bicarbonate — the logic that also underlies its altitude use. It is contraindicated in hyperchloremic acidosis and used with caution in pulmonary obstruction or emphysema, where it may precipitate or aggravate acidosis.

Adverse effects

Common — acetazolamide, methazolamide

Tingling in the hands, feet or face (paresthesias), fatigue, drowsiness, loss of appetite, taste alteration, nausea, vomiting, diarrhea, increased urination, and hearing changes or tinnitus.

Metabolic acidosis and electrolyte loss

Metabolic acidosis and electrolyte imbalance with both drugs; acetazolamide’s label names hypokalemia and hyponatremia, and methazolamide increases potassium excretion at first.

Serious sulfonamide reactions

Rarely fatal Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias, and anaphylaxis.

Kidney stones and crystalluria (CAIs)

Crystalluria and kidney stones, with a higher risk of nephrolithiasis on long-term acetazolamide therapy.

Eye: myopia and choroidal effusion (acetazolamide)

Transient myopia; choroidal effusion and detachment have been reported after eye surgery.

Fluid overload and dehydration (mannitol)

Hypervolemia that can cause or worsen heart failure and pulmonary edema; or dehydration and hypovolemia from the osmotic diuresis.

Kidney injury (mannitol)

Acute kidney injury, osmotic nephrosis and, rarely, irreversible renal failure.

CNS toxicity and rebound intracranial pressure (mannitol)

Confusion, lethargy and coma, some fatal; a rebound rise in intracranial pressure several hours after the infusion.

Hypersensitivity (mannitol)

Serious reactions, including anaphylaxis, hypotension and dyspnea that have led to cardiac arrest and death.

Infusion site reactions (mannitol)

Phlebitis and inflammation from a hypertonic solution in a peripheral vein; compartment syndrome and swelling with extravasation.

Hyperchloremic (normal anion gap) metabolic acidosis: Inhibiting proximal carbonic anhydrase wastes bicarbonate in the urine; serum HCO₃⁻ falls and chloride moves into the plasma to replace the lost negative charge. It can be severe in older adults with reduced kidney function, and chronic acidosis is believed to cause growth retardation in children on long-term therapy.
Hypokalemia: More sodium reaches the distal nephron, where it is reabsorbed in exchange for potassium; bicarbonate also carries potassium out with it. Mannitol causes hypokalemia the same way, through increased distal sodium delivery.
Kidney stones and crystalluria: Bicarbonate excretion alkalinizes the urine, which favors stone formation: crystalluria and an increased risk of nephrolithiasis with long-term therapy are labeled effects, and taking sodium bicarbonate with acetazolamide raises the risk further. Drinking water with each dose helps prevent them.
Hepatic encephalopathy in cirrhosis: Urinary alkalinization increases ammonia reabsorption by the renal tubules, and acetazolamide decreases ammonia clearance — so in cirrhosis the drug may precipitate hepatic encephalopathy, and it is contraindicated.
Stevens-Johnson syndrome, blood dyscrasias, fulminant hepatic necrosis: These are reactions of the sulfonamide structure; liver injury is presumed to reflect cross-reactivity with sulfonamide reactions and appears days to weeks after starting. HLA-B*5901 is strongly associated with methazolamide-induced SJS/TEN.
Transient myopia: Forward movement of the ciliary body narrows the angle.
Pulmonary edema and heart failure (mannitol): Raising serum osmolality shifts water from the cells into the plasma, expanding blood volume before the diuresis; overt extracellular expansion can precipitate pulmonary edema in heart failure, and in anuria the volume is not cleared.
Hyponatremia, then hypernatremia (mannitol): Water drawn from the cells into the plasma first dilutes the plasma sodium; the osmotic diuresis can then cause dehydration, hemoconcentration and hypernatremia.
Worse cerebral edema and rebound intracranial pressure (mannitol): Mannitol more easily crosses injured vessels, as in intracranial hemorrhage; with frequent doses it can cross the blood–brain barrier and draw water into the brain instead of out of it. A rebound rise in intracranial pressure may occur several hours after the infusion, with a higher risk when the barrier is compromised.
Acute kidney injury (mannitol): Mannitol can cause osmotic injury to the tubules (osmotic nephrosis, acute tubular necrosis); oliguric acute kidney injury has followed large IV doses even with normal kidney function, and nephrotoxic drugs or other diuretics add to the risk.

Toxicity & antidote

With acetazolamide, overdose is expected to cause electrolyte imbalance, an acidotic state and CNS effects. There is no specific antidote: serum electrolytes (particularly potassium) and blood pH are monitored, the acidosis can usually be corrected with bicarbonate, and acetazolamide is dialyzable — useful when overdose is complicated by renal failure.

Mannitol overdose causes acute kidney injury, hypo- or hypervolemia, hyperosmolarity, electrolyte imbalance and CNS toxicity such as coma or seizures. The infusion is stopped, fluid and electrolytes are corrected with attention to the kidneys, heart and lungs, and hemodialysis can increase its elimination.

Interactions

Acetazolamide or methazolamide + high-dose aspirin

Anorexia, tachypnea, lethargy, coma and death have been reported with the combination (acetazolamide also lists metabolic acidosis) — use caution.

Acetazolamide + phenytoin

Raises phenytoin levels and may increase osteomalacia on chronic phenytoin — use caution.

Acetazolamide + primidone

Decreases primidone absorption and levels, so the anticonvulsant effect may fall — use caution when starting, stopping or changing acetazolamide.

Acetazolamide + another carbonic anhydrase inhibitor

Possible additive effects — concomitant use is not advisable.

Acetazolamide + amphetamines or quinidine

Acetazolamide reduces their urinary excretion and may enhance their effect.

Acetazolamide + lithium

Increases lithium excretion, so the lithium level may fall.

Acetazolamide + sodium bicarbonate

Raises the risk of kidney stones.

Acetazolamide + methenamine, cyclosporine, folic acid antagonists or antidiabetic agents

May prevent methenamine’s urinary antiseptic effect, may raise cyclosporine levels, may increase the effects of other folic acid antagonists, and may raise or lower blood glucose.

Methazolamide + corticosteroids

Use with caution because of the potential for hypokalemia.

Mannitol + nephrotoxic drugs (cyclosporine, aminoglycosides) or other diuretics

Increase the risk of renal failure — avoid the combination if possible.

Mannitol + neurotoxic drugs (e.g. aminoglycosides)

May potentiate mannitol’s CNS toxicity — avoid if possible.

Mannitol + drugs sensitive to electrolyte shifts (digoxin, QT-prolonging drugs, neuromuscular blockers)

Mannitol-induced hypo- or hyperkalemia may cause cardiac adverse reactions — monitor electrolytes and stop mannitol if cardiac status worsens.

Mannitol + lithium

May first increase lithium elimination, then raise the risk of lithium toxicity if hypovolemia or kidney impairment develops — consider holding lithium and monitor levels frequently. Mannitol may also reduce the effect of other drugs that are mainly renally eliminated.

Contraindications

Low serum sodium or potassium, marked kidney or liver disease, adrenal failure, or hyperchloremic acidosis (acetazolamide, methazolamide) — Labeled contraindication — these drugs cause sodium and potassium loss and metabolic acidosis.
Cirrhosis (acetazolamide, methazolamide) — Labeled contraindication — use may precipitate hepatic encephalopathy.
Long-term use in chronic angle-closure glaucoma (acetazolamide: noncongestive angle-closure; methazolamide: angle-closure) — Labeled contraindication — the angle may close organically while the lowered pressure masks the worsening glaucoma.
Hypersensitivity to acetazolamide — Labeled contraindication — acetazolamide is a sulfonamide derivative, so cross-sensitivity with other sulfonamides is possible.
Mannitol: known hypersensitivity, anuria, severe hypovolemia, severe pulmonary vascular congestion or pulmonary edema, or active intracranial bleeding (except during craniotomy) — Labeled contraindications — the patient cannot safely take on the volume shift or excrete the drug.
Pulmonary obstruction or emphysema with impaired alveolar ventilation (acetazolamide, methazolamide) use caution — Use with caution — the drugs may precipitate or aggravate acidosis.
High-dose aspirin (acetazolamide, methazolamide) use caution — Caution — anorexia, tachypnea, lethargy, coma and death have been reported with the combination.
Mannitol with kidney disease, nephrotoxic drugs or other diuretics, or a compromised blood–brain barrier use caution — Not contraindicated, but the risk of renal failure, or of rebound intracranial pressure and worsening cerebral edema, is higher.

High-yield

Normal anion gap metabolic acidosis with an alkaline urine Carbonic anhydrase inhibitor (acetazolamide)

Carbonic anhydrase sites in the proximal tubule Luminal (brush border) and cytosolic — acetazolamide blocks both

Diuretic that lowers CSF production in idiopathic intracranial hypertension Acetazolamide (choroid plexus)

Altitude prophylaxis: how the acidosis helps Compensatory hyperventilation raises PaO₂

Oral CAI for glaucoma that should not be used as a diuretic Methazolamide

HLA allele linked to methazolamide-induced SJS/TEN HLA-B*5901

Filtered, less than 10% reabsorbed, not secreted Mannitol (osmotic diuretic)

Osmotic diuretic contraindicated in anuria and pulmonary edema Mannitol

Why acetazolamide fails in renal insufficiency It must be secreted into the tubule (organic anion transporters) to act

Why patients on a carbonic anhydrase inhibitor drink water with each dose Urinary alkalinization favors kidney stones

ACETAZOLAMIDE makes the urine BASIC and the blood ACIDIC

Urine: bicarbonate escapes the proximal tubule → alkaline urine (and a risk of kidney stones)
Blood: serum HCO₃⁻ falls, chloride replaces it → hyperchloremic, normal anion gap metabolic acidosis
Breathing: the acidosis drives hyperventilation → used for altitude sickness

The falling bicarbonate also leaves less for the drug to act on, so the diuresis fades.

Practice questions

Q1A 34-year-old woman with idiopathic intracranial hypertension has taken acetazolamide for 3 months. Her labs show sodium 139, chloride 113 and bicarbonate 16 mEq/L, and her urine pH is 7.5.

Which mechanism best explains the acid–base change?

A.Accumulation of an unmeasured organic acid from drug metabolism
B.Bicarbonate wasting from blocked proximal-tubule carbonic anhydrase, with chloride retained in its place
C.Loss of sodium-rich, bicarbonate-poor fluid concentrating the serum bicarbonate
D.Hyperventilation that lowers PaCO₂ as the primary disturbance

Show answer

B. Bicarbonate wasting from blocked proximal-tubule carbonic anhydrase, with chloride retained in its place — Acetazolamide blocks luminal and cellular carbonic anhydrase in the proximal tubule, so filtered bicarbonate is lost (bicarbonaturia) and the urine is alkaline; serum HCO₃⁻ falls and chloride replaces the lost negative charge, giving a normal anion gap (here 10), hyperchloremic metabolic acidosis. Acetazolamide is not metabolized, so there is no unmeasured acid. Losing sodium-rich, bicarbonate-poor fluid causes a contraction alkalosis — the loop diuretics’ pattern — which would raise, not lower, the bicarbonate. Hyperventilation is the compensation for the acidosis, not its cause.

Q2A 45-year-old man with heart failure receives acetazolamide for edema. After a brisk diuresis on the first day, his urine output falls back toward baseline over the next few days even though he takes the same dose, and his serum bicarbonate has fallen.

Why has the diuretic effect waned?

A.Acetazolamide induces its own hepatic metabolism
B.The dose is now too low, and a higher dose would restore the diuresis
C.Protein binding stops acetazolamide from reaching the tubular lumen
D.The falling serum bicarbonate leaves less substrate for carbonic anhydrase–dependent reabsorption, and distal segments reclaim the extra sodium

Show answer

D. The falling serum bicarbonate leaves less substrate for carbonic anhydrase–dependent reabsorption, and distal segments reclaim the extra sodium — As bicarbonaturia lowers serum bicarbonate, less substrate is available for carbonic anhydrase–mediated sodium reabsorption, so acetazolamide becomes less efficient; the loop, distal tubule and ENaC-bearing nephron also reabsorb the extra sodium delivered to them. Acetazolamide is not metabolized, so it does not induce its own metabolism, and protein-bound diuretics reach the lumen by tubular secretion rather than filtration. A higher dose would not help: the label notes that increasing the dose does not increase the diuresis, and it gives edema doses intermittently so the kidney can recover.

Q3A 70-year-old man with cerebral edema and raised intracranial pressure after a cardiac arrest is given IV mannitol. He has heart failure with reduced ejection fraction. An hour into the infusion he becomes dyspneic, with new crackles at both lung bases.

What is the most likely explanation?

A.Mannitol has crossed the blood–brain barrier and caused neurogenic pulmonary edema
B.Anaphylaxis to mannitol
C.Hypokalemia from the osmotic diuresis
D.Metabolic acidosis from carbonic anhydrase inhibition
E.Mannitol has shifted water from the cells into the plasma, expanding the circulation before the diuresis

Show answer

E. Mannitol has shifted water from the cells into the plasma, expanding the circulation before the diuresis — Mannitol raises plasma osmolality and draws water out of the cells into the plasma, increasing blood volume before the kidneys excrete it; overt expansion of extracellular volume can precipitate pulmonary edema in heart failure, and severe pulmonary vascular congestion or edema contraindicates it. Entry into the brain worsens cerebral edema rather than the lungs. Anaphylaxis would bring hypotension and other allergic signs, hypokalemia does not cause crackles, and mannitol does not inhibit carbonic anhydrase.

Q4A 52-year-old woman with cirrhosis and ascites is started on acetazolamide by mistake. Within days she becomes confused and has asterixis.

Which effect of the drug best explains her deterioration?

A.Hyperkalemia from distal potassium retention
B.Metabolic alkalosis from bicarbonate retention
C.Urinary alkalinization that increases tubular ammonia reabsorption
D.Fluid retention from an osmotic action in the plasma

Show answer

C. Urinary alkalinization that increases tubular ammonia reabsorption — Urinary alkalinization increases the renal tubular reabsorption of ammonia, and acetazolamide decreases ammonia clearance, so it may precipitate hepatic encephalopathy — which is why both CAIs are contraindicated in cirrhosis. CAIs increase potassium excretion rather than retaining it, and in hepatic insufficiency that potassium loss could itself precipitate hepatic coma. They waste bicarbonate and cause a hyperchloremic metabolic acidosis, not an alkalosis, and the osmotic plasma expansion belongs to mannitol, not to a carbonic anhydrase inhibitor.

Q5A 61-year-old man with chronic kidney disease (creatinine clearance 18 mL/min) has open-angle glaucoma that topical drops do not control. His ophthalmologist considers oral acetazolamide.

Why is acetazolamide likely to be both less effective as a diuretic and more hazardous in him?

A.It is activated by the liver, which is impaired in CKD
B.It must be secreted into the proximal tubule to act and is cleared by the kidney, so poor renal function blunts its effect and favors metabolic acidosis
C.It is a potassium-sparing drug and will cause hyperkalemia
D.It is filtered and not reabsorbed, so it causes volume overload
E.It is so protein-bound that dialysis cannot remove it in overdose

Show answer

B. It must be secreted into the proximal tubule to act and is cleared by the kidney, so poor renal function blunts its effect and favors metabolic acidosis — Acetazolamide reaches its luminal target by secretion through the proximal tubule’s organic anion transporters; almost 90% is excreted by tubular secretion, and it is ineffective in renal insufficiency. Marked kidney disease is a labeled contraindication, and metabolic acidosis can be severe when renal function is reduced. It is not metabolized (so not a prodrug), it causes hypokalemia rather than hyperkalemia, filtration without reabsorption describes mannitol, and despite its protein binding acetazolamide is dialyzable.

Sources

By LearnDrugs

Educational summary for medical students. Always verify against current prescribing information and guidelines. Not medical advice.