Pharm Heart Failure

1. A 63-year-old man complained to his physician of nausea, vomiting and visual sensation of green-yellow halos around bright objects. The man, recently diagnosed with cardiac failure and atrial fibrillation, had started an appropriate treatment two weeks previously. Which of the following drugs most likely caused the patient's symptoms?

Verapamil

Propranolol

Digoxin

Lidocaine

Furosemide

Captopril

Learning objective: Describe the main adverse effects of digoxin.
Answer: C
The most solid indication for digoxin is still the combination of chronic cardiac failure with atrial
fibrillation. Because of its direct AV blocking effects and vagomimetic properties digoxin reduces
the number of impulses conducted through the AV node an therefore controls the ventricular
response rates in patients with atrial fibrillation. Most likely digoxin was included in the patient’s
management and the symptoms of the patient are classic symptoms of digitalis toxicity.
A, B) These drugs can control the ventricular response rates in patients with atrial fibrillation
since they decrease AV conduction. However they do not cause the symptoms the patient is
complaining of.
D, E) These drugs do not decrease AV conduction and are of no value in atrial fibrillation.

Explanation

Learning objective: Describe the main adverse effects of digoxin.
Answer: C
The most solid indication for digoxin is still the combination of chronic cardiac failure with atrial
fibrillation. Because of its direct AV blocking effects and vagomimetic properties digoxin reduces
the number of impulses conducted through the AV node an therefore controls the ventricular
response rates in patients with atrial fibrillation. Most likely digoxin was included in the patient’s
management and the symptoms of the patient are classic symptoms of digitalis toxicity.
A, B) These drugs can control the ventricular response rates in patients with atrial fibrillation
since they decrease AV conduction. However they do not cause the symptoms the patient is
complaining of.
D, E) These drugs do not decrease AV conduction and are of no value in atrial fibrillation.

2. A 72-year-old man was admitted to the hospital because of anuria. The man had a long history of severe systolic cardiac failure and chronic obstructive pulmonary disease. Shortly after the admission the patient started vomiting, then become agitated, verbally abusive, and disoriented in space and time. He was telling the nurse that he heard laud voices cursing him. An ECG showed atrial tachycardia with AV block. Which of the following drugs most likely caused the patient's symptoms?

Captopril

Digoxin

Ipratropium

Metoprolol

Ethacrynic acid

Albuterol

Learning objective: describe the digoxin induced arrhythmias.
Answer: B
A patient with severe systolic dysfunction was most likely receiving a cardiac therapy that
included digoxin. The patient probably developed an acute renal failure (as indicated by the
sudden anuria) which increased substantially the toxicity of digoxin. In fact patient’s symptoms
are typical of the so called “digitalis delirium.”
A, C, D, E) These drugs do not cross the blood-brain barrier so central effects are unlikely.
F) Albuterol crosses the blood-brain barrier and may cause feelings of apprehension and anxiety
but not the symptoms exhibited by the patient.

Explanation

Learning objective: describe the digoxin induced arrhythmias.
Answer: B
A patient with severe systolic dysfunction was most likely receiving a cardiac therapy that
included digoxin. The patient probably developed an acute renal failure (as indicated by the
sudden anuria) which increased substantially the toxicity of digoxin. In fact patient’s symptoms
are typical of the so called “digitalis delirium.”
A, C, D, E) These drugs do not cross the blood-brain barrier so central effects are unlikely.
F) Albuterol crosses the blood-brain barrier and may cause feelings of apprehension and anxiety
but not the symptoms exhibited by the patient.

3. A 61-year-old man, recently diagnosed with stage C heart failure, was admitted to the hospital for a control visit. It was found that he had an ejection fraction of 30% at rest and a treatment which included digoxin was started. Which of the following cardiovascular parameters did digoxin most likely increase in this patient?

Stroke volume

Total peripheral resistance

Oxygen consumption of the heart

End-diastolic volume

Heart rate

Learning objective: Describe the hemodynamic actions of digoxin in the failing heart.
Answer: A
The increase in stroke volume is a direct consequence of the positive inotropic action of digitalis
glycosides.
B) Digoxin can cause peripheral vasoconstriction in the normal subject, but causes instead
peripheral vasodilation in patients with cardiac failure because the increased cardiac output
offsets the reactive vasoconstriction.
C) Digoxin actually decreases oxygen consumption in the failing heart because:
1) The increased contractility reduces the left ventricular end diastolic volume and so the stretch
of the cardiac fibers (oxygen consumption of the heart is directly proportional to the stretch of the
cardiac fibers).
2) The increased cardiac output offsets the tachycardia induced by the sympathetic activation.
D, E) (see explanation of item C).

Explanation

Learning objective: Describe the hemodynamic actions of digoxin in the failing heart.
Answer: A
The increase in stroke volume is a direct consequence of the positive inotropic action of digitalis
glycosides.
B) Digoxin can cause peripheral vasoconstriction in the normal subject, but causes instead
peripheral vasodilation in patients with cardiac failure because the increased cardiac output
offsets the reactive vasoconstriction.
C) Digoxin actually decreases oxygen consumption in the failing heart because:
1) The increased contractility reduces the left ventricular end diastolic volume and so the stretch
of the cardiac fibers (oxygen consumption of the heart is directly proportional to the stretch of the
cardiac fibers).
2) The increased cardiac output offsets the tachycardia induced by the sympathetic activation.
D, E) (see explanation of item C).

4. A 73-year-old man complained to his physician of increasing fatigue and increasing shortness of breath which was often worse at night forcing him to "sit bolt upright". He also noticed that his feet were getting swollen. Past history of the patient was unremarkable. Vital signs were: blood pressure 150/90, respiratory rate 17/min. On examination a mild pitting edema was seen on the legs. An ECG disclosed a second degree AV block. The physician diagnosed an initial cardiac failure and prescribed an appropriate therapy. Which of the following drugs would be contraindicated for this patient?

Captopril

Hydrochlorothiazide

Digoxin

Losartan

Furosemide

Spironolactone

Learning objective: describe the main contraindication of digoxin.
Answer: C
Digoxin is relatively contraindicated in patient with significant AV block, since the drug
decreases AV conduction due both to the parasympathomimetic action and to the direct
depressive effect on the AV node. Since the patient is hypertensive all the other listed drugs are
appropriate for initial heart failure or for hypertension.
A, B, D, E, F) (see explanation above)

Explanation

Learning objective: describe the main contraindication of digoxin.
Answer: C
Digoxin is relatively contraindicated in patient with significant AV block, since the drug
decreases AV conduction due both to the parasympathomimetic action and to the direct
depressive effect on the AV node. Since the patient is hypertensive all the other listed drugs are
appropriate for initial heart failure or for hypertension.
A, B, D, E, F) (see explanation above)

5. A 68-year-old man recently diagnosed with heart failure, started a treatment with metoprolol, losartan, furosemide and digoxin. Which of the following molecular actions most likely mediated the positive inotropic action of digoxin?

Closing of calcium channels in cardiac cell membranes

Increased release of Ca++ from sarcoplasmic reticulum during systole

Activation of Na+/K+ ATPase

Activation of Ca++/Na+ exchanger in cardiac cell membranes

Opening of K+ channels in cardiac cell membranes

Learning objective: explain the molecular mechanism of action digoxin.
Answer: B
At the molecular level all cardiac glycosides inhibit Na+/K+ ATPase, the membrane bound
transporter called the sodium pump. The increased amount of sodium inside the cell inhibits the
Ca++/Na+ exchanger, an antiport that uses the electrochemical potential for Na+ to drive Ca++
extrusion. The consequence of this inhibition is that less Ca++ is removed from the cell. The
increased intracellular calcium is stored in the sarcoplasmic reticulum during diastole, and
therefore a greater amount of Ca++ is released from the sarcoplasmic reticulum during systole.
A) Digitalis glycosides (at high concentration) can open, not close, cardiac calcium channels.
C, D) (see explanation above)
E) Digitalis glycosides have no effect on potassium channels.

Explanation

Learning objective: explain the molecular mechanism of action digoxin.
Answer: B
At the molecular level all cardiac glycosides inhibit Na+/K+ ATPase, the membrane bound
transporter called the sodium pump. The increased amount of sodium inside the cell inhibits the
Ca++/Na+ exchanger, an antiport that uses the electrochemical potential for Na+ to drive Ca++
extrusion. The consequence of this inhibition is that less Ca++ is removed from the cell. The
increased intracellular calcium is stored in the sarcoplasmic reticulum during diastole, and
therefore a greater amount of Ca++ is released from the sarcoplasmic reticulum during systole.
A) Digitalis glycosides (at high concentration) can open, not close, cardiac calcium channels.
C, D) (see explanation above)
E) Digitalis glycosides have no effect on potassium channels.

6. Directions: questions 1-5 Match each drug used in cardiac failure with the appropriate description (each lettered option can be selected once, more than once, or not at all): This drug can cause peripheral vasodilation by increasing the synthesis of cGMP

Captopril

Digoxin

Dobutamine

Furosemide

Losartan

Milrinone

Nesiritide

Propranolol

Spironolactone

Nesiritide is the correct answer because it can cause peripheral vasodilation by increasing the synthesis of cGMP.

Explanation

Nesiritide is the correct answer because it can cause peripheral vasodilation by increasing the synthesis of cGMP.

7. A 62-year-old woman was admitted to the hospital complaining of nausea, mental confusion, dizziness and palpitations. The woman, suffering from hypertension and recurrent atrial fibrillation, had been receiving furosemide, captopril and digoxin for several months. One week ago she started erythromycin and ibuprofen for an acute upper respiratory tract infection. Which of the following events most likely caused the patient's symptoms?

Furosemide-induced hypokalemia

Erythromycin-induced increase in digoxin oral bioavailability

Furosemide-induced hypocalcemia

Captopril-induced decrease in digoxin clearance

Ibuprofen-induced decrease in digoxin clearance

Learning objective: describe the digoxin drug interaction of clinical importance.
Answer: B
Broad spectrum antibiotics like erythromycin can increase the oral bioavailability of digoxin
because they kill bacteria present in normal intestinal flora (mainly Eubacterium lentum) which
are able to metabolize digoxin. This is a major and clinically important drug interaction with
digoxin.
A) Even if hypokalemia can increase digoxin toxicity this is quite unlikely in the present case,
since the patient has been receiving furosemide and digoxin for several months without adverse
effects.
C) Hypercalcemia, not hypocalcemia, can increase digoxin toxicity.
D) Captopril can rarely decrease digoxin renal excretion but this is quite unlikely in the present
case for the reasons explained above
E) Ibuprofen can rarely decrease digoxin renal excretion but the effect is transient and clinically
unimportant.

Explanation

Learning objective: describe the digoxin drug interaction of clinical importance.
Answer: B
Broad spectrum antibiotics like erythromycin can increase the oral bioavailability of digoxin
because they kill bacteria present in normal intestinal flora (mainly Eubacterium lentum) which
are able to metabolize digoxin. This is a major and clinically important drug interaction with
digoxin.
A) Even if hypokalemia can increase digoxin toxicity this is quite unlikely in the present case,
since the patient has been receiving furosemide and digoxin for several months without adverse
effects.
C) Hypercalcemia, not hypocalcemia, can increase digoxin toxicity.
D) Captopril can rarely decrease digoxin renal excretion but this is quite unlikely in the present
case for the reasons explained above
E) Ibuprofen can rarely decrease digoxin renal excretion but the effect is transient and clinically
unimportant.

8. A 61-year-old alcoholic male was admitted to the hospital with a 2-day history of epigastric pain associated with nausea and vomiting. The man had been suffering from systolic heart failure for two years. Present medications were captopril, furosemide and digoxin. Pertinent serum data on admission were: K+ 2.8 mEq/L, creatinine 3.2 mg/dL. An ECG showed an heart rate of 65 bpm with occasional premature ventricular contractions and runs of bigeminy. Which of the following would be an appropriate therapeutic conduct for this patient?

Add potassium supplementation and reduce digoxin dosage

Add atropine and reduce digoxin dosage

Increase furosemide dosage and reduce digoxin dosage

Discontinue digoxin and start losartan

Discontinue digoxin and start milrinone

Learning objective: describe the therapy of digoxin toxicity.
Answer: A
The symptoms the patient was referring to (nausea and vomiting) as well as the arrhythmia
shown by the ECG, are classical signs of digitalis toxicity. Furosemide treatment most likely
caused hypokalemia which is a well recognized predisposing factor to digitalis toxicity. In fact in
patients with serum K+ of 3 mEq/L, the dose of digoxin needed to produce toxicity is about one
half of that needed in patients with serum K+ of 5 mEq/L. Moreover the patient had a reduced
renal function (see the creatinine serum level) which most likely decreased the renal excretion of
digoxin.
A potassium supplementation is the rational therapy in case of hypokalemia. The dosage of
digoxin must also be reduced because of the renal insufficiency.
B) This strategy would be used when digoxin toxicity is due to an excessive
parasympathomimetic activity of the drug (which is usually suggested by the presence of a
severe bradycardia or by an AV block).
C) This option is irrational: a reduced digoxin dosage would, of course, reduce toxicity, but an
increased furosemide dosage would worsen the hypokalemia.
D) Digoxin was quite effective for three years, which indicates that the heart failure was serious
enough to require an inotropic drug. Therefore it would be irrational to withdraw an inotropic
medication.
E) Milrinone is an effective inotropic drug but, because of its toxicity, is used only when other
drugs are not able to improve the symptoms of the disease. When a drug is effective but causes
adverse effects (like in this case) the first procedure to follow is to adjust the dosage.

Explanation

Learning objective: describe the therapy of digoxin toxicity.
Answer: A
The symptoms the patient was referring to (nausea and vomiting) as well as the arrhythmia
shown by the ECG, are classical signs of digitalis toxicity. Furosemide treatment most likely
caused hypokalemia which is a well recognized predisposing factor to digitalis toxicity. In fact in
patients with serum K+ of 3 mEq/L, the dose of digoxin needed to produce toxicity is about one
half of that needed in patients with serum K+ of 5 mEq/L. Moreover the patient had a reduced
renal function (see the creatinine serum level) which most likely decreased the renal excretion of
digoxin.
A potassium supplementation is the rational therapy in case of hypokalemia. The dosage of
digoxin must also be reduced because of the renal insufficiency.
B) This strategy would be used when digoxin toxicity is due to an excessive
parasympathomimetic activity of the drug (which is usually suggested by the presence of a
severe bradycardia or by an AV block).
C) This option is irrational: a reduced digoxin dosage would, of course, reduce toxicity, but an
increased furosemide dosage would worsen the hypokalemia.
D) Digoxin was quite effective for three years, which indicates that the heart failure was serious
enough to require an inotropic drug. Therefore it would be irrational to withdraw an inotropic
medication.
E) Milrinone is an effective inotropic drug but, because of its toxicity, is used only when other
drugs are not able to improve the symptoms of the disease. When a drug is effective but causes
adverse effects (like in this case) the first procedure to follow is to adjust the dosage.

9. A 65-year-old man was brought to the emergency room in acute distress. He was agitated, incoherent, disoriented in time and space, and seemed to be hallucinating. The patient had been suffering from severe chronic cardiac failure for two years and his wife referred she found an empty bottle of digoxin tablets near the husband's bed. Vital sings of the patient were: blood pressure 100/50 mm Hg, heart rate 45 bpm. An emergency treatment was instituted and a drug was given IV. Which of the following drugs was most likely administered?

Lidocaine

Atropine

Phenytoin

Potassium chloride

Digoxin antibodies

Amiodarone

Learning objective: describe the treatment of digoxin poisoning.
Answer: E
The history and the patient’s symptoms indicated that the patient attempted suicide by ingesting
several digoxin tablets. The best way to treat digoxin poisoning is to administer digoxin
antibodies (digoxin immune Fab) that bind digoxin with very high affinity, so removing the drug
from its tissue binding sites. They are extremely effective in reversing digoxin intoxication.
A, B, C, D, F) All these drugs may be used in case of digoxin toxicity, to treat specific digoxininduced
cardiac symptoms (i.e. lidocaine in case of ventricular tachycardia, atropine in case of
AV block, etc.) However when poisoning is severe and many body functions are seriously
affected (see the psychic symptoms of the patient) digoxin antibodies must be administered first.

Explanation

Learning objective: describe the treatment of digoxin poisoning.
Answer: E
The history and the patient’s symptoms indicated that the patient attempted suicide by ingesting
several digoxin tablets. The best way to treat digoxin poisoning is to administer digoxin
antibodies (digoxin immune Fab) that bind digoxin with very high affinity, so removing the drug
from its tissue binding sites. They are extremely effective in reversing digoxin intoxication.
A, B, C, D, F) All these drugs may be used in case of digoxin toxicity, to treat specific digoxininduced
cardiac symptoms (i.e. lidocaine in case of ventricular tachycardia, atropine in case of
AV block, etc.) However when poisoning is severe and many body functions are seriously
affected (see the psychic symptoms of the patient) digoxin antibodies must be administered first.

10. Directions: questions 1-5 Match each drug used in cardiac failure with the appropriate description (each lettered option can be selected once, more than once, or not at all): This drug can increase central parasympathetic firing

Captopril

Digoxin

Dobutamine

Furosemide

Losartan

Milrinone

Nesiritide

Propranolol

Spironolactone

Digoxin can increase central parasympathetic firing.

Explanation

Digoxin can increase central parasympathetic firing.

11. Directions: questions 1-5 Match each drug used in cardiac failure with the appropriate description (each lettered option can be selected once, more than once, or not at all): This drug can cause peripheral vasodilation by increasing cAMP levels.

Captopril

Digoxin

Dobutamine

Furosemide

Losartan

Milrinone

Nesiritide

Propranolol

Spironolactone

Milrinone is a drug used in cardiac failure that can cause peripheral vasodilation by increasing cAMP levels.

Explanation

Milrinone is a drug used in cardiac failure that can cause peripheral vasodilation by increasing cAMP levels.

12. A 42-year-old man was admitted to the hospital in acute distress with breathlessness, markedly distended neck veins and atrial fibrillation. The blood pressure was 100/90 mm Hg, the pulse 120 bpm. An echocardiogram revealed an ejection fraction of 35%. A treatment was started with furosemide, captopril and digoxin. In this patient digoxin most likely decreased which of the following cardiovascular parameters?

Stroke volume

End-systolic volume

End diastolic volume

Systolic pressure

Pulse pressure

Learning objective: Describe the hemodynamic actions of cardiac glycosides in the failing
heart.
Answer: B
An inotropic drug increases the force of heart contraction and therefore a higher fraction of the
end-diastolic volume is ejected during systole. As a consequence the end systolic volume (that is
the volume of blood remaining in the ventricle at the end of the systole) is decrease.
A) All inotropic drugs increase, not decrease, the stroke volume.
C) The end-diastolic volume (that is the volume of blood filling the ventricles at the end of the
diastole) is the sum of the end systolic volume plus the stroke volume. Since the stroke volume
is increased, and the end systolic volume is decreased by inotropic drugs, the end diastolic
volume is not significantly changed.
D) Digoxin increases, not decreases, the systolic blood pressure in patient with cardiac failure
because of the increase in cardiac output.
E)Pulse pressure may be sharply decreased in patients with heart failure since systolic pressure
cannot be maintained because of the decrease in cardiac output, whereas diastolic pressure is
normal or increased because of sympathetic activation. By increasing cardiac output digoxin
increases the systolic pressure and offsets the reactive, sympathetically-mediated
vasoconstriction. Therefore the pulse pressure is increased, not decreased.

Explanation

Learning objective: Describe the hemodynamic actions of cardiac glycosides in the failing
heart.
Answer: B
An inotropic drug increases the force of heart contraction and therefore a higher fraction of the
end-diastolic volume is ejected during systole. As a consequence the end systolic volume (that is
the volume of blood remaining in the ventricle at the end of the systole) is decrease.
A) All inotropic drugs increase, not decrease, the stroke volume.
C) The end-diastolic volume (that is the volume of blood filling the ventricles at the end of the
diastole) is the sum of the end systolic volume plus the stroke volume. Since the stroke volume
is increased, and the end systolic volume is decreased by inotropic drugs, the end diastolic
volume is not significantly changed.
D) Digoxin increases, not decreases, the systolic blood pressure in patient with cardiac failure
because of the increase in cardiac output.
E)Pulse pressure may be sharply decreased in patients with heart failure since systolic pressure
cannot be maintained because of the decrease in cardiac output, whereas diastolic pressure is
normal or increased because of sympathetic activation. By increasing cardiac output digoxin
increases the systolic pressure and offsets the reactive, sympathetically-mediated
vasoconstriction. Therefore the pulse pressure is increased, not decreased.

13. A 54-year-old woman presented to the hospital complaining of palpitations. The woman, recently diagnosed with stage C heart failure, started a therapy with metoprolol, digoxin and captopril one month ago. Her medications also included estrogens and calcium supplement for postmenopausal osteoporosis. Patient's vital signs were: blood pressure 145/90, pulse 130 bpm. An ECG showed ventricular tachycardia. Significant plasma levels on admission were: K 5.8 mEq/L, Ca 12.2 mEq/L, creatinine 3.5 mg/dL . Which of the following events most likely triggered the patient's arrhythmia?

The metoprolol-induced decrease in cardiac contractility

The increased serum K+ level

The captopril-induced vasodilation

The increased serum Ca++ level

The estrogen-induced hypertension

Learning objective: describe the factors that enhance the risk of digoxin toxicity.
Answer: D
Ventricular tachycardia is a serious adverse effect of digoxin. The reduced renal function of the
patient (see the creatinine serum level) most likely decreased the renal excretion of digoxin, so
increasing the risk of adverse effects. Digoxin toxicity is enhanced by many factors including
hypercalcemia, which accelerates the overloading of intracellular calcium stores. An increased
intracellular calcium appears to be responsible for an increased abnormal automaticity.
A, B, C, E) (see explanation above)

Explanation

Learning objective: describe the factors that enhance the risk of digoxin toxicity.
Answer: D
Ventricular tachycardia is a serious adverse effect of digoxin. The reduced renal function of the
patient (see the creatinine serum level) most likely decreased the renal excretion of digoxin, so
increasing the risk of adverse effects. Digoxin toxicity is enhanced by many factors including
hypercalcemia, which accelerates the overloading of intracellular calcium stores. An increased
intracellular calcium appears to be responsible for an increased abnormal automaticity.
A, B, C, E) (see explanation above)

14. A 65-year-old woman presented to the hospital with a chief complain of palpitations. The woman suffering from stage C heart failure had been receiving digoxin, furosemide and losartan for six months. Laboratory data on admission included: potassium 3.9 mEq/L (normal: 3.5 – 5.0), calcium 9.2 mg/dL (normal: 8.5 – 10.5), magnesium 2.5 mEq/L (normal 1.5 – 2.0) total T4 42 ng/mL (normal 50-110), TSH 15 mIU/mL (normal 0.5-5.5). An ECG showed junctional tachycardia that, according to the physician, was most likely due to digoxin treatment. Which of the following pathological conditions most likely increased the risk of digoxin toxicity in this patient?

Hypermagnesemia

Hyperaldosteronism

Hyperparathyroidism

Concomitant furosemide treatment

Hypothyroidism

Learning objective: describe the factors that enhance the risk of digoxin toxicity.
Answer: E
The patient is suffering from hypothyroidism, as indicated by the low T4 and the high TSH levels.
Hypothyroidism increases the risk of digitalis toxicity because elimination of digoxin is decreased
and the heart is more sensitive to digitalis.
A) Hypomagnesemia, not hypermagnesemia can increase digitalis toxicity.
B) Hyperaldosteronism is unlikely since potassium levels are normal.
C) Hyperparathyroidism is unlikely since calcium levels are normal.
D) Concomitant furosemide treatment can increase digoxin toxicity mainly by causing hypokalemia, but this is quite unlike in the present case, since the patient has been receiving
furosemide and digoxin for several months without adverse effects, and potassium levels are
normal

Explanation

Learning objective: describe the factors that enhance the risk of digoxin toxicity.
Answer: E
The patient is suffering from hypothyroidism, as indicated by the low T4 and the high TSH levels.
Hypothyroidism increases the risk of digitalis toxicity because elimination of digoxin is decreased
and the heart is more sensitive to digitalis.
A) Hypomagnesemia, not hypermagnesemia can increase digitalis toxicity.
B) Hyperaldosteronism is unlikely since potassium levels are normal.
C) Hyperparathyroidism is unlikely since calcium levels are normal.
D) Concomitant furosemide treatment can increase digoxin toxicity mainly by causing hypokalemia, but this is quite unlike in the present case, since the patient has been receiving
furosemide and digoxin for several months without adverse effects, and potassium levels are
normal

15. Directions: questions 1-5 Match each drug used in cardiac failure with the appropriate description (each lettered option can be selected once, more than once, or not at all): The chronic use of this diuretic can reduce mortality in patients with heart failure

Captopril

Digoxin

Dobutamine

Furosemide

Losartan

Milrinone

Nesiritide

Propranolol

Spironolactone

Spironolactone is a diuretic that is commonly used in the treatment of heart failure. It works by blocking the effects of aldosterone, a hormone that can contribute to fluid retention in patients with heart failure. Studies have shown that chronic use of spironolactone can reduce mortality in patients with heart failure, making it an important medication in the management of this condition.

Explanation

Spironolactone is a diuretic that is commonly used in the treatment of heart failure. It works by blocking the effects of aldosterone, a hormone that can contribute to fluid retention in patients with heart failure. Studies have shown that chronic use of spironolactone can reduce mortality in patients with heart failure, making it an important medication in the management of this condition.

16. Directions: questions 1-5 Match each drug used in cardiac failure with the appropriate description (each lettered option can be selected once, more than once, or not at all): This drug can increase the synthesis of cAMP in the heart

Captopril

Digoxin

Dobutamine

Furosemide

Losartan

Milrinone

Nesiritide

Propranolol

Spironolactone

Dobutamine is the correct answer because it is a sympathomimetic drug that acts as a beta-1 adrenergic receptor agonist, which can increase the synthesis of cAMP in the heart.

Explanation

Dobutamine is the correct answer because it is a sympathomimetic drug that acts as a beta-1 adrenergic receptor agonist, which can increase the synthesis of cAMP in the heart.

17. A 57-year-old man suffering from persistent atrial fibrillation started a treatment with digoxin, one tablet daily. Which of the following actions most likely mediated the therapeutic effect of digoxin in the present case?

Opening of Ca++ channels of cardiac cell membranes

Stimulation of vagal activity

Blockade of Ca++/Na+ exchanger

Blockade of Na+/K+ pump

Inhibition of phosphodiesterase

Learning objective: describe the main action leading to the therapeutic effect of digoxin in
atrial fibrillation.
Answer: B
Digoxin is still used in persistent atrial fibrillation (even if it is no longer a first-line therapy)
because it can decrease the AV conduction, so decreasing the high ventricular rate. This is
accomplished by a stimulation of vagal activity due to:
1) stimulation of vagal nucleus
2) sensitization of carotid sinus baroreceptors
3) facilitation of muscarinic transmission at the cardiac muscle cells.
A, C, D) Digoxin does have all these actions but these are important for the positive inotropic
activity, not for the decrease in the AV conduction.
E) Cardiac glycosides do not inhibit phosphodiesterase.

Explanation

Learning objective: describe the main action leading to the therapeutic effect of digoxin in
atrial fibrillation.
Answer: B
Digoxin is still used in persistent atrial fibrillation (even if it is no longer a first-line therapy)
because it can decrease the AV conduction, so decreasing the high ventricular rate. This is
accomplished by a stimulation of vagal activity due to:
1) stimulation of vagal nucleus
2) sensitization of carotid sinus baroreceptors
3) facilitation of muscarinic transmission at the cardiac muscle cells.
A, C, D) Digoxin does have all these actions but these are important for the positive inotropic
activity, not for the decrease in the AV conduction.
E) Cardiac glycosides do not inhibit phosphodiesterase.

18. A 57-year-old woman suffering from persistent atrial flutter started a treatment with digoxin, one tablet daily. Which of the following cardiac actions most likely occurred during the therapy?

Increased end systolic volume

Decreased abnormal cardiac automaticity

Decreased diastolic time

Increased atrial refractoriness

Decreased heart rate

Learning objective: describe the cardiac actions of digoxin.
Answer: E
Digoxin decreases heart rate both in the normal and in failing heart (unless toxic effects of the
drug supervene) due to a decreases AV conduction, which is a consequence of a direct action
and of a parasympathomimetic action on the AV node.
A) By increasing contractility digoxin decreases, not increase, the end systolic volume
B) Digoxin dose-dependently increases abnormal cardiac automaticity, as indicated by many
varieties of arrhythmia caused by the drug.
C) By causing bradycardia digoxin increases, not decreases the diastolic time.
D) Atrial refractoriness is decreased, not increased, by digoxin, due both to a direct action and of
a parasympathomimetic action of the drug.

Explanation

Learning objective: describe the cardiac actions of digoxin.
Answer: E
Digoxin decreases heart rate both in the normal and in failing heart (unless toxic effects of the
drug supervene) due to a decreases AV conduction, which is a consequence of a direct action
and of a parasympathomimetic action on the AV node.
A) By increasing contractility digoxin decreases, not increase, the end systolic volume
B) Digoxin dose-dependently increases abnormal cardiac automaticity, as indicated by many
varieties of arrhythmia caused by the drug.
C) By causing bradycardia digoxin increases, not decreases the diastolic time.
D) Atrial refractoriness is decreased, not increased, by digoxin, due both to a direct action and of
a parasympathomimetic action of the drug.

19. A 63-year-old woman, admitted to the hospital for a control visit, was found to have a third degree AV block. The woman, who had been suffering from stage C heart failure, had been receiving captopril, furosemide and digoxin for two months and the disease was well controlled. The physician believed that the block was due to digoxin therapy. Which of the following would be an appropriate therapeutic conduct for this patient?

Discontinue digoxin and start milrinone

Add physostigmine and decrease digoxin dose

Add atropine and decrease digoxin dose

Discontinue digoxin and start metoprolol

Add dobutamine and decrease digoxin dose

Discontinue digoxin and start losartan

Learning objective: outline the therapy for a digoxin induced AV block.
Answer: C
A Digoxin-induced AV block is most likely due, at least in part, to the parasympathomimetic
action of digoxin. Therefore a treatment with atropine and a reduction of digoxin dosage is a
rational therapeutic approach.
A) Milrinone is used only for short-term IV treatment of patients with end-stage heart failure.
B) Physostigmine is a cholinergic drug and therefore it would worsen the AV block.
D) To discontinue digoxin would be irrational since the ongoing therapy was effective. Moreover
metoprolol is contraindicated in case of AV block.
E) Beta-adrenergic agonists are used only for short-term IV treatment of patients with acute
cardiac failure. Moreover, even if a beta-adrenergic agonist can increase the ventricular rate in
patients with AV block due to increased vagal activity, it acts as a physiological antagonist of
acetylcholine. In this case atropine is much better since a pharmacological antagonist is superior
to a physiological antagonist in most cases.
F) (see explanation D)

Explanation

Learning objective: outline the therapy for a digoxin induced AV block.
Answer: C
A Digoxin-induced AV block is most likely due, at least in part, to the parasympathomimetic
action of digoxin. Therefore a treatment with atropine and a reduction of digoxin dosage is a
rational therapeutic approach.
A) Milrinone is used only for short-term IV treatment of patients with end-stage heart failure.
B) Physostigmine is a cholinergic drug and therefore it would worsen the AV block.
D) To discontinue digoxin would be irrational since the ongoing therapy was effective. Moreover
metoprolol is contraindicated in case of AV block.
E) Beta-adrenergic agonists are used only for short-term IV treatment of patients with acute
cardiac failure. Moreover, even if a beta-adrenergic agonist can increase the ventricular rate in
patients with AV block due to increased vagal activity, it acts as a physiological antagonist of
acetylcholine. In this case atropine is much better since a pharmacological antagonist is superior
to a physiological antagonist in most cases.
F) (see explanation D)

20. A 68-year-old woman recently diagnosed with C heart failure, started a treatment with digoxin, 1 tablet daily. Knowing that digoxin has a CL of 7L/h and an oral bioavailability of 70%, which of the following doses was most likely given to achieve a steady state plasma concentration of 1 ng/mL?

1.4

0.125

0.24

2.0

0.5

2.4

Learning objective: calculate the maintenance dose of digoxin, given sufficient data.
Answer: C
A maintenance dose of a drug is given by: D = (Css x Cl) / F. Therefore:
Dose = (1 mcg/L x 7L/h) / 0.7 = 10 mcg/h = 240 mcg daily
A, B, D, E, F) (see explanation above)

Explanation

Learning objective: calculate the maintenance dose of digoxin, given sufficient data.
Answer: C
A maintenance dose of a drug is given by: D = (Css x Cl) / F. Therefore:
Dose = (1 mcg/L x 7L/h) / 0.7 = 10 mcg/h = 240 mcg daily
A, B, D, E, F) (see explanation above)