1.
Directions: questions 1-5
Match each diuretic with the appropriate description (each lettered option can be selected once,
more than once, or not at all):
This drug inhibits Na+ reabsorption in the proximal tubule
Correct Answer
A. Acetazolamide
Explanation
Acetazolamide is a diuretic that inhibits the reabsorption of sodium in the proximal tubule of the kidney. This action prevents the reabsorption of water, leading to increased urine production. Acetazolamide is commonly used to treat conditions such as glaucoma, altitude sickness, and certain types of epilepsy.
2.
Directions: questions 1-5
Match each diuretic with the appropriate description (each lettered option can be selected once,
more than once, or not at all):
This drug inhibits the synthesis of new Na+ channels in the collecting duct
Correct Answer
G. Spironolactone
Explanation
Spironolactone is the correct answer because it is a potassium-sparing diuretic that works by inhibiting the synthesis of new Na+ channels in the collecting duct. This action prevents the reabsorption of sodium and water, leading to increased urine production and decreased fluid retention.
3.
Directions: questions 1-5
Match each diuretic with the appropriate description (each lettered option can be selected once,
more than once, or not at all):
This drug causes an initial extracellular volume expansion in normal subjects
Correct Answer
F. Mannitol
Explanation
Mannitol is a diuretic that causes an initial extracellular volume expansion in normal subjects.
4.
Directions: questions 1-5
Match each diuretic with the appropriate description (each lettered option can be selected once,
more than once, or not at all):
This drug increases the renal reabsorption of Ca++
Correct Answer
E. Indapamide
Explanation
Indapamide is the correct answer because it is a diuretic that increases the renal reabsorption of Ca++. Acetazolamide, Amiloride, Conivaptan, Ethacrynic acid, Mannitol, Spironolactone, and Triamterene do not have this specific effect.
5.
Directions: questions 1-5
Match each diuretic with the appropriate description (each lettered option can be selected once,
more than once, or not at all):
This drug competitively blocks ADH receptors
Correct Answer
C. Conivaptan
Explanation
Conivaptan is the correct answer because it competitively blocks ADH receptors. The other diuretics listed do not have this specific mechanism of action. Acetazolamide is a carbonic anhydrase inhibitor, Amiloride and Triamterene are potassium-sparing diuretics, Ethacrynic acid is a loop diuretic, Indapamide is a thiazide-like diuretic, Mannitol is an osmotic diuretic, and Spironolactone is an aldosterone antagonist.
6.
A 56-year old woman recently diagnosed with congestive heart failure, started a
therapy which included furosemide. Acetazolamide was also added to counteract the
potential metabolic alkalosis induced by furosemide. Which of the following molecular
actions most likely mediated the therapeutic effect of acetazolamide in this patient?
Correct Answer
A. Inhibition of carbonic acid dehydration in the tubular lumen
Explanation
Learning objective: explain the molecular mechanism of diuretic action of carbonic
anhydrase inhibitors.
Answer: A
Carbonic anhydrase is an enzyme located in the brush border and in the cytoplasm of the cells
of proximal convolute tubule. In the proximal tubule a large amount of H+ is secreted into the
lumen via a Na+/H+ exchanger. Most of this H+ combines with bicarbonate ion in the tubular
fluid to form carbonic acid which is rapidly dehydrated to CO2 and water (this reaction is
catalyzed by carbonic anhydrase). The CO2 diffuses into the proximal tubular cells where the
opposite reaction takes places to form H+ and HCO3 (this reaction too is catalyzed by carbonic
-
anhydrase). The HCO3 exits the cell on the basolateral side and is therefore reabsorbed as
-
bicarbonate. Hydrogen ion is secreted into the lumen via the Na+/H+ exchanger. Acetazolamide
is a carbonic anhydrase inhibitor. By blocking the enzyme it blocks the reabsorption of
bicarbonate and Na+ , resulting in an increase in diuresis.
B) Acetazolamide cause an inhibition, not a simulation of bicarbonate reabsorption.
C) This would be the mechanism of action of thiazides.
D) hydrogen is not reabsorbed by the kidney . By inhibiting carbonic anhydrase, acetazolamide
inhibits the formation of carbonic acid inside the tubular cells, which in turn inhibits the secretion
of hydrogen into the lumen.
E) Acetazolamide cause an inhibition, not a stimulation, of carbonic acid formation inside the
tubular cells.
7.
A 27-year-old woman with a history of high altitude sickness was placed on
prophylactic treatment with a diuretic drug prior to going on a hiking trip to the Rocky
Mountains. Which of the following urine electrolyte profiles is most consistent with this
drug treatment?(+ increased in urine; - decreased in urine; 0 no change in urine)
Correct Answer
A. A
Explanation
Learning objective: describe the urine profile of a patient treated with carbonic anhydrase
inhibitors
Answer: A
Acetazolamide, a carbonic anhydrase inhibitor, is the only diuretic used to prevent mountain
sickness in persons who are at risk for this disorder and have to go to a high altitude. The
mechanism of this action is not clear but it may be related to the induction of metabolic acidosis.
Carbonic anhydrase inhibitors produce an urine which is very rich in bicarbonate. Urinary
sodium is only slightly increased (the efficacy of these diuretic is low). Urinary K+ excretion is
also increased (all diuretics, but potassium sparing diuretics increase urinary K+ excretion).
B) This urine profile would be caused by osmotic diuretic
C) This urine profile would be caused by thiazides
D) This urine profile would be caused by loop diuretics
E) This urine profile would be caused by K+ sparing diuretic
8.
A 69-year-old depressed man, who has been suffering from glaucoma for ten years,
was admitted to the emergency room after he took several tablets of one of his
medications in a suicide attempt. The patient was drowsy an complained of nausea,
paresthesias and tiredness. Physical examination disclosed an erythematous skin
eruption and lab exams showed hyperchloremic metabolic acidosis. Which of the
following medications might have caused the patient’s these symptoms?
Correct Answer
D. Acetazolamide
Explanation
Learning objective: describe the main adverse effects of carbonic anhydrase inhibitors.
Answer: D
The symptoms of the patients are classic symptoms of acetazolamide overdose. The drug is
used for glaucoma because it decreases the production of aqueous humor, a fluid which is rich
in bicarbonate. High doses of carbonic anhydrase inhibitors like acetazolamide can cause
metabolic acidosis since they profoundly increase the urinary excretion of bicarbonate. Because
the plasma loss of bicarbonate is counterbalanced by an in crease of extracellular Cl-, most
metabolic acidosis are hyperchloremic.
A, B, C, E) All these listed drugs are used for glaucoma, but they do not cause hyperchloremic
metabolic acidosis.
9.
A 55-year-old alcoholic man was admitted to the hospital because of disorientation,
amnesia, confusion and bizarre behavior of 24 hour duration. His wife reported that the
man was under therapy for hypertension and for a recently diagnosed glaucoma. Physical
examination revealed a cachectic male in a confused mental state. Abdomen appeared
tense with prominent veins and ascites and a musty ,pungent odor was noted in his
breath. Neurological sings included nystagmus, ataxia and asterixis. Which of the
following drugs most likely triggered the patient’s syndrome?
Correct Answer
A. Acetazolamide
Explanation
Learning objective: describe the main adverse effects of carbonic anhydrase inhibitors.
Answer: A
The history, the symptoms and signs of the patient suggest that he was suffering from
portal-systemic encephalopathy, a syndrome that can occur when extensive portal-systemic
collaterals have developed as a result of portal hypertension. Liver cirrhosis is one of the most
common causes of portal-systemic encephalopathy, and this was most likely the cause in the
present case. Carbonic anhydrase inhibitors cause urine alkalinization which in turn reduces
urinary excretion of ammonia. The resulting hyperammonemia is an important cause of portasystemic
encephalopathy, since NH 4+ causes brain toxicity. Likely the ophthalmologist
overlooked the possible cirrhosis of the patient and prescribed acetazolamide for glaucoma.
B, C, D, E) These drugs do not trigger liver encephalopathy in patient at risk.
10.
A 54-year-old woman recently diagnosed with open angle glaucoma was prescribed
topical timolol. Two weeks later the intraocular pressure was decreased but was still
above the normal value. The ophthalmologist decided to add another topical drug that act
by decreasing aqueous humor production. Which of the following drugs was most likely
prescribed?
Correct Answer
D. Dorzolamide
Explanation
Learning objective: describe the main therapeutic uses of carbonic anhydrase inhibitors.
Answer: D
Dorzolamide is a carbonic anhydrase inhibitors. The rationale of the use of these drugs in open
angle glaucoma is based on the fact that aqueous humor is rich in bicarbonate. By inhibiting
bicarbonate synthesis, the production of aqueous humor is decreased.
A, B, C, E) All these drugs are used in glaucoma but they act by increasing the outflow, not by
decreasing the production, of the aqueous humor
11.
A 15-year-old boy awoke with weakness and an hour later realized he could not move
his legs. The attack lasted about 2 hours, then it disappeared without residual symptoms.
The boy was referred to a neurologic clinic where the diagnosis of familial hypokalemic
periodic paralysis was made. He was prescribed potassium chloride and a diuretic that is
able to prevent the attacks in many cases. Which of the following drugs was most likely
prescribed?
Correct Answer
E. Acetazolamide
Explanation
Learning objective: describe the main therapeutic uses of carbonic anhydrase inhibitors.
Answer: E
Familial hypokalemic periodic paralysis is a rare autosomal condition characterized by episodes
of flaccid paralysis with loss of deep tendon reflex. Potassium flows from the bloodstream into
muscle cells during attacks. Acetazolamide may help to prevent the attacks; the mechanism of
action is still uncertain, but it could be related to the production of metabolic acidosis which
decreases the activity of Na+/K+ ATPase, so lowering the entry of potassium into muscle cells.
A, B, C) These diuretics can cause hypokalemia and therefore are contraindicated in this
disease.
D) Potassium sparing diuretics are sometimes used in hypokalemic periodic paralysis but they
are not needed in this case since a potassium supplementation was prescribed.
12.
A 67-year-old man was found to have a plasma level of calcium of 12.2 mg/dL. during
a followup visit. The man, who had been suffering from Hodgkin’s lymphoma for three
years, was recently diagnosed with nephrolithiasis and started a therapy with
hydrochlorothiazide three weeks previously. Which of the following statements best
explains the most likely mechanism of thiazide induced hypercalcemia?
Correct Answer
A. Enhancement of Na+/Ca++ exchanger in the distal tubule
Explanation
Learning objective: explain the mechanism of thiazides induced hypercalcemia.
Answer: A
In the kidney, the distal convolute tubule reabsorbs about 8% of the filtered Ca++ load. This
reabsorption occurs through epithelial Ca++ channels. In the steady state however the cell must
extrude all the entered Ca++ and this occurs through a plasma membrane Ca++ ATPase (the
Ca++ pump) and also through a Na+/Ca++ exchanger located on the basolateral surface of cells
of the distal tubule. Thiazides inhibit the Na+/Cl- symport in the early distal convolute tubule, so
decreasing the intracellular concentration of Na. This likely enhances the activity of the
Na+/Ca++ exchanger which in turn creates a greater driving force for reabsorption of Ca++
through the epithelial Ca++ channels. The final effect is an increased reabsorption of Ca++ that
can cause hypercalcemia or, more often, can unmask hypercalcemia due to other causes , like
in the present case (malignancy is a common cause of hypercalcemia).
B, C, D, E, F) Thiazides do not cause these effects.
13.
A 67-year old woman was found to have a plasma level of potassium 3.8 mEq/L during
a followup visit. The woman, recently diagnosed with essential hypertension, started a
therapy with hydrochlorothiazide one month previously. Which of the following actions
most likely contributed to the thiazide-induced increase of renal excretion of potassium?
Correct Answer
A. Increased Na+ load in the lumen of the collecting tubule
Explanation
Learning objective: explain the mechanism of thiazide-induced increase of renal excretion
of potassium
Answer: A
Potassium secretion by the distal tubule is a passive process that depends on the
electrochemical gradient between the distal tubular cells an the tubular lumen. The higher the
NA+ load in the distal tubule, the higher NA+ reabsorption. This creates a lumen negative
potential which favors K+ excretion.
B) Thiazides do not inhibit this cotransporter.
C) Thiazide can decrease the secretion of uric acid but this has nothing to do with the thiazide
induced increase in K+ excretion.
D) Thiazide do not stimulate the Na+/K+ pump.
E) Thiazides are weak carbonic anhydrase inhibitors and therefore tend to increase, not to
decrease, the delivery of bicarbonate to the collecting duct.
14.
A 65-year-old man was found to have a plasma level of calcium of 12.2 mg/dL. during
a followup visit. The man, who had been suffering from Hodgkin’s lymphoma for three
years, was recently diagnosed with nephrolithiasis and started a therapy with
hydrochlorothiazide three weeks previously. Which of the following statements best
explains the most likely mechanism of thiazide induced hypercalcemia?
Correct Answer
A. Enhancement of Na+/Ca++ exchanger in the distal tubule
Explanation
Learning objective: explain the mechanism of thiazide-induced hypercalcemia.
Answer: A
In the kidney, the distal convolute tubule reabsorbs about 8% of the filtered Ca++ load. This
reabsorption occurs through epithelial Ca++ channels. In the steady state however the cell must
extrude all the entered Ca++ and this occurs through a plasma membrane Ca++ ATPase (the
Ca++ pump) and also through a Na+/Ca++ exchanger located on the basolateral surface of cells
of the distal tubule. Thiazides inhibit the Na+/Cl- symport in the early distal convolute tubule, so
decreasing the intracellular concentration of Na. This likely enhances the activity of the
Na+/Ca++ exchanger which in turn creates a greater driving force for reabsorption of Ca++
through the epithelial Ca++ channels. The final effect is an increased reabsorption of Ca++ that
can cause hypercalcemia or, more often, can unmask hypercalcemia due to other causes , like
in the present case (malignancy is a common cause of hypercalcemia).
B, C, D, E, F) Thiazides do not cause these effects.
15.
A 76-year-old woman from a nursing home presented to the emergency room with a
change in her mental state over the past few hours. She had a medical history of coronary
artery disease and hypertension. Her medications included aspirin, captopril , lovastatin
and a diuretic. On physical examination she showed a decreased skin turgor, orthostatic
hypotension, disorientation to time, place and person, without focal neurologic deficits.
Pertinent blood test results on admission were Na 125 mEq/L, creatinine 2.7 mg/dL. Which
of the following drugs most likely caused the patient syndrome?
Correct Answer
F. Indapamide
Explanation
Learning objective: identify the diuretics that can cause hyponatremia.
Answer: F
The patient symptoms and signs suggest the diagnosis of dilutional hyponatremia, which is a
rare (but sometimes fatal) adverse effect of thiazide diuretics. These drugs affect the diluting
ability of the kidney while increasing Na+ excretion. Once volume depletion occurs the release
of ADH cause water retention and worsens the hyponatremia. In contrast loop diuretics (not
shown in the question) affect also the concentrating ability of the kidney so limiting the ADH
mediated water retention. The effect of thiazides may last 1-2 weeks after cessation of the
therapy. Elderly patients are especially prone to thiazide-induced hyponatremia, particularly if a
preexisting renal insufficiency exists, like in the present case (see high creatinine level).
A, B, C, D, E) The risk of dilutional hyponatremia with these drugs is negligible.
16.
A 47-year-old woman suffering from metastatic breast cancer was admitted to the
hospital because of a persistent thirst and polyuria. Admission lab data were: serum K 2.8
mEq/L, Ca 16.2 mg/dL, Na 155 mEq/L. Urinalysis: specific gravity 1.001, osmolality 80
mOsm/L (range 50-1440), protein and microscope negative. The patient was given a water
deprivation test: all fluids were withheld until serum osmolality increased into the
hyperosmolar range (> 310), then 5 units of vasopressin were given SC. Results are
tabulated below:
Which of the following drugs would be most appropriate to treat the patient’s condition?
Correct Answer
B. Hydrochlorothiazide
Explanation
Learning objective: describe the therapeutic use of thiazides in diabetes insipidus.
Answer: B
Polyuria with low urine osmolality suggests the diagnosis of diabetes insipidus. To determine the
cause of this syndrome vasopressin is used. Nephrogenic diabetes insipidus is vasopressinresistant,
so that urine osmolality would not change significantly after vasopressin, as in the
present case. A common cause of nephrogenic diabetes insipidus is hypercalcemia which is
common in bone metastases of various tumors. Thiazide diuretics can reduce polyuria and
polydipsia in diabetes insipidus. The mechanism of this paradoxical effect is related to
the extracellular volume reduction which in turn causes an enhanced proximal reabsorption of
NA+ and water in the proximal tubule and a decrease delivery of fluid to the distal tubule. Thus
the maximum volume of dilute urine that can be produced is lowered.
A) Desmopressin is effective in neurogenic diabetes insipidus but is ineffective in nephrogenic
diabetes insipidus. Neurogenic diabetes insipidus is unlikely because it is vasopressin-sensitive
and therefore urine osmolality would have been increased significantly after vasopressin.
C) Demeclocycline is appropriate in case of the syndrome of inappropriate ADH secretion. This
syndrome leads to hyponatremia (not hypernatremia, like in diabetes insipidus) and low serum
osmolality.
D) Amiloride is used effectively in case of lithium-induced nephrogenic diabetes insipidus
because the drug blocks lithium transport into the cells of the collecting tubule. However it is not
effective in other forms of diabetes insipidus.
E) Furosemide is not effective in nephrogenic diabetes insipidus. It can be used in case of
chronic renal failure but this diagnosis is unlikely in the present case because the urine
osmolality is lower than serum osmolality (in chronic renal failure urine osmolality is usually fixed
close to that of serum).
17.
A 63-year-old man with a long history of heart failure was admitted to the hospital
because of severe dyspnea and edema on legs, thighs and lower abdominal wall.
Pertinent lab results on admission included a GFR of 25 mL/min. A diuretic with which of
the following mechanism of action would be appropriate to relieve the edema of this
patient?
Correct Answer
C. Blockade of Na+/K+/2Cl- symport in the Henle’s loop
Explanation
Learning objective: explain the molecular mechanism of action of loop diuretics.
Answer: C
When the GFR is less than 30 mL/min (as it can occur in case of severe heart failure) the only
diuretics that are still active are loop diuretics. This is likely related, at least in part, to the fact
that, by inhibiting NA+ and Cl- transport into the macula densa, the macula densa is no longer
able to sense salt concentration in the tubular fluid, and therefore increases renin secretion
leading to an increase in angiotensin II. Because angiotensin II preferentially constricts the
efferent arteriole, GFR is enhanced.
A, B, D, E) (see explanation above)
18.
A 42-year-old obese female was hospitalized because of hypokalemia despite a daily
administration of potassium supplement. Laboratory tests upon admission revealed
metabolic alkalosis. The patient admitted taking furosemide tablets in an effort to loose
weight. Which of the following actions might contribute to furosemide-induced metabolic
alkalosis in this patient?
Correct Answer
B. The increase delivery of Na+ to the distal tubule
Explanation
Learning objective: explain the molecular mechanism of furosemide-induced metabolic
alkalosis.
Answer: B
There are three main causes of alkalosis induced by loop diuretics. The most important is the
increase delivery of Na+ to the distal tubule. The consequent increased reabsorption of Na+
creates a luminal negative potential which favors both H+ and K+ excretion. The second cause
is the stimulation of aldosterone release due to volume contraction and increased renin
secretion. The third cause can occur only when hypokalemia is severe. In this case K+ tends to
leave the cell and H+ enters to maintain electroneutrality with the final result of extracellular
alkalosis and intracellular acidosis.
A, C, D,) All these are action of loop diuretics but these actions do not lead to metabolic
alkalosis
E) Loop diuretics actually increase renin secretion.
19.
A 78-year-old man from a nursing home presented to the emergency room with a
change in his mental state over the past few hours. He had a medical history of angina
and hypertension presently treated with isosorbide mononitrate, losartan and
hydrochlorothiazide. Physical examination showed a person with decreased skin turgor,
disorientation to time and place, without focal neurologic deficits. Blood pressure was
110/65 mm Hg on standing and 140/88 mm Hg on laying. Pertinent blood tests on
admission were: Na 116 q/L, K 3.1 mEq/L, uric acid 10.2 mg/dL, creatinine 3.7 mg/dL. The
physician thought that the syndrome was due to diuretic therapy. Which of the following
drug-induced adverse effects most likely caused the patient’s symptoms and signs ?
Correct Answer
C. Hypovolemic hyponatremia
Explanation
Learning objective: explain the mechanism of thiazide-induced extracellular volume depletion.
Answer: C
The patient symptoms and signs suggest the diagnosis of hypovolemic hyponatremia which is a
rare (but sometimes fatal) adverse effects of thiazide diuretics. These drugs affect the diluting
ability of the kidney while increasing Na+ excretion. Once volume depletion occurs, the release
of ADH cause water retention and worsens hyponatremia. This effect of thiazides may last 1-2
weeks after cessation of the therapy. Elderly patients are especially prone to thiazide-induced
hyponatremia, particularly if a preexisting renal insufficiency exists, like in the present case (see
high creatinine level).
A, B, D) These disorders do not cause the symptoms and signs showed by the patient.
E) The patient is hyponatremic, but the postural hypotension and the diuretic therapy indicate
that hyponatremia is hypovolemic, not hypervolemic
20.
A 66-year-old woman suffering from systolic cardiac failure was brought to the
emergency room because of a sudden onset of extreme dyspnea. She presented with
cyanosis, tachypnea, hyperpnea, restlessness, anxiety and a sense of suffocation. Cough
was prominent and produced pink-tinged, frothy sputum. Pulse was thready and fast (120
bpm), blood pressure 80/45 mm Hg and rales were audible at the lung bases. Which of the
following drugs was most likely included in the immediate medical treatment of this
patient?
Correct Answer
E. Furosemide
Explanation
Learning objective: describe the main therapeutic uses of loop diuretics.
Answer: E
The patient exhibits the classic symptoms of pulmonary edema. Furosemide is the diuretic of
first choice for this condition because it is able to quickly reduce preload (and therefore the left
ventricular filling pressure) through the following actions:
a) A rapid increase in venous capacitance, likely mediated by prostaglandin release.(the initial
beneficial effect may result more from this action than from diuresis).
b) A brisk and abundant natriuresis
A, B) These diuretics are less effective than loop diuretics and do not have acute vasodilating
properties.
C, D, F) These drugs are contraindicated in pulmonary edema