Block 11 - Week 12 - Heart Failure Drugs

1. Healthy volunteers were given IV a new anti-anginal drug in a phase 1 clinical trial. The results are summarized in the following table:

Parameter	Drug effect
Heart rate	Decreased
Peripheral vascular resistance	Increased
End-diastolic volume	Increased
Ejection time	Increased

Which of the following drugs does the new agent most resemble?

Nitroglycerin

Isosorbide mononitrate

Nifedipine

Verapamil

Propranolol

The new agent most resembles Propranolol because it decreases heart rate, increases peripheral vascular resistance, increases end-diastolic volume, and increases ejection time. Propranolol is a beta-blocker that works by blocking the effects of adrenaline on the beta receptors in the heart, leading to a decrease in heart rate and blood pressure. It also increases peripheral vascular resistance, which can help in the treatment of angina.

Explanation

The new agent most resembles Propranolol because it decreases heart rate, increases peripheral vascular resistance, increases end-diastolic volume, and increases ejection time. Propranolol is a beta-blocker that works by blocking the effects of adrenaline on the beta receptors in the heart, leading to a decrease in heart rate and blood pressure. It also increases peripheral vascular resistance, which can help in the treatment of angina.

2. A 96-year-old African American female was admitted from a nursing home with complaints of abdominal pain, nausea, vomiting, dizziness, confusion and double vision for 5 days. She was discharged from the hospital just 4 days ago. Digoxin was started during that previous hospitalization for control of tachycardia in atrial fibrillation. One day prior to discharge, her digoxin level was 1.8 mg/mL. Now , considering the toxicity of digoxin, the digoxin dose was decreased to 125 mcg PO Q 48 hr. Her past medical history shows that she has hypertension, hypercholesterolemia, has congestive heart failure, and occasional episodes of atrial fibrillation. Her present medication includes metoprolol, digoxin, ASA (aspirin), cholestyramine, niacin and furosemide. The reason why this patient developed digoxin toxicity is:

Hyperkalemia increases the risk of digoxin toxicity

Hypokalemia increases the risk of digoxin toxicity

Metoprolol inhibits the metabolism of digoxin

Furosemide causes hemoconcentration

Hypokalemia increases the risk of digoxin toxicity because low levels of potassium can enhance the binding of digoxin to its target receptor, the sodium-potassium ATPase pump. This increases the concentration of digoxin in the body, leading to toxicity. Digoxin toxicity can cause symptoms such as abdominal pain, nausea, vomiting, dizziness, confusion, and visual disturbances, which are consistent with the patient's presentation. The patient's history of atrial fibrillation and congestive heart failure also puts her at a higher risk for digoxin toxicity.

Explanation

Hypokalemia increases the risk of digoxin toxicity because low levels of potassium can enhance the binding of digoxin to its target receptor, the sodium-potassium ATPase pump. This increases the concentration of digoxin in the body, leading to toxicity. Digoxin toxicity can cause symptoms such as abdominal pain, nausea, vomiting, dizziness, confusion, and visual disturbances, which are consistent with the patient's presentation. The patient's history of atrial fibrillation and congestive heart failure also puts her at a higher risk for digoxin toxicity.

3. A 63 –year- old man with a history of chronic hypertension was admitted with advanced systolic cardiac failure and edema of the lower limbs. Which of the following options would be best suited to treat his condition?

Digoxin, hydrochlorothiazide, metoprolol, triamterene

Digoxin, furosemide, metoprolol, lisinopril

Digoxin, dorzolamide, furosemide, amiloride

Digoxin, acetazolamide, spironolactone, atenolol

The correct answer is Digoxin, furosemide, metoprolol, lisinopril. This combination of medications is commonly used in the treatment of advanced systolic cardiac failure and edema of the lower limbs. Digoxin helps to improve heart function, furosemide is a diuretic that helps to reduce fluid buildup, metoprolol is a beta-blocker that helps to reduce the workload on the heart, and lisinopril is an ACE inhibitor that helps to relax blood vessels and improve blood flow. Together, these medications can help to alleviate symptoms and improve the overall condition of the patient.

Explanation

The correct answer is Digoxin, furosemide, metoprolol, lisinopril. This combination of medications is commonly used in the treatment of advanced systolic cardiac failure and edema of the lower limbs. Digoxin helps to improve heart function, furosemide is a diuretic that helps to reduce fluid buildup, metoprolol is a beta-blocker that helps to reduce the workload on the heart, and lisinopril is an ACE inhibitor that helps to relax blood vessels and improve blood flow. Together, these medications can help to alleviate symptoms and improve the overall condition of the patient.

4. A 50-year-old woman complained of shortness of breath and dyspnea on mild physical exertion. Her medical history revealed a previous myocardial infarction and a recent diagnosis of left ventricular failure. She had an ejection fraction of 27%. The cardiologist decided to start her on oral digoxin therapy along with the other medications she has been taking. Which of the following molecular actions most likely mediated the therapeutic effect of digoxin in the patient's disorder?

Activation of Na+ /K+ ATPase

Decreased intracellular Na+

Activation of cardiac M2 receptors

Inhibition of Ca++/Na+ exchanger

Digoxin is a medication commonly used in the treatment of heart failure. In this patient's case, the therapeutic effect of digoxin is most likely mediated by the inhibition of the Ca++/Na+ exchanger. This action of digoxin helps to increase the intracellular concentration of calcium, leading to improved contractility of the heart muscle. By inhibiting the Ca++/Na+ exchanger, digoxin helps to enhance the force of contraction and improve cardiac output in patients with heart failure. This can alleviate symptoms such as shortness of breath and dyspnea on exertion.

Explanation

Digoxin is a medication commonly used in the treatment of heart failure. In this patient's case, the therapeutic effect of digoxin is most likely mediated by the inhibition of the Ca++/Na+ exchanger. This action of digoxin helps to increase the intracellular concentration of calcium, leading to improved contractility of the heart muscle. By inhibiting the Ca++/Na+ exchanger, digoxin helps to enhance the force of contraction and improve cardiac output in patients with heart failure. This can alleviate symptoms such as shortness of breath and dyspnea on exertion.

5. A 62-year-old man recently diagnosed with stage C systolic heart failure started a therapy which included an Ace inhibitor, a beta-blocker and a loop diuretic. Which of the following statements best explains why loop diuretics are by far more effective than thiazide diuretics?

Loop diuretics increase renin secretion

Loop diuretics are also weak inhibitors of carbonic anhydrase

The diuretic effect of thiazides undergoes partial tolerance

More sodium is physiologically reabsorbed at TALH than at DCT

The antihypertensive action of thiazides reduces GFR

Loop diuretics are more effective than thiazide diuretics because more sodium is physiologically reabsorbed at the thick ascending limb of the loop of Henle (TALH) than at the distal convoluted tubule (DCT). Loop diuretics inhibit the sodium-potassium-chloride co-transporter in the TALH, preventing the reabsorption of sodium and other ions. This results in a greater diuretic effect compared to thiazide diuretics, which primarily act on the DCT to inhibit sodium reabsorption.

Explanation

Loop diuretics are more effective than thiazide diuretics because more sodium is physiologically reabsorbed at the thick ascending limb of the loop of Henle (TALH) than at the distal convoluted tubule (DCT). Loop diuretics inhibit the sodium-potassium-chloride co-transporter in the TALH, preventing the reabsorption of sodium and other ions. This results in a greater diuretic effect compared to thiazide diuretics, which primarily act on the DCT to inhibit sodium reabsorption.

6. A 54-year-old man was found to have a second degree A-V block during a control visit. The man, suffering from chronic heart failure, had been receiving digoxin for two months. The physician thought the block was most likely due to digoxin therapy. Which of the following drugs would be appropriate to counteract this adverse effect of digoxin?

Isoproterenol

Atropine

Lidocaine

Potassium chloride

Atenolol

Atropine would be appropriate to counteract the adverse effect of digoxin in this case. Digoxin can cause A-V block, and atropine is a medication that can increase heart rate and improve conduction through the A-V node. By blocking the effects of the parasympathetic nervous system, atropine can help to counteract the bradycardic effects of digoxin and improve the A-V conduction.

Explanation

Atropine would be appropriate to counteract the adverse effect of digoxin in this case. Digoxin can cause A-V block, and atropine is a medication that can increase heart rate and improve conduction through the A-V node. By blocking the effects of the parasympathetic nervous system, atropine can help to counteract the bradycardic effects of digoxin and improve the A-V conduction.

7. 61-year-old man with a long history of chronic heart failure was brought to the emergency room in a confused state. His wife reported she found an empty bottle of digoxin oral solution and thought her husband drunk all the bottle in a suicide attempt. Upon admission the patient was confused and exhibited hallucinatory behavior. His blood pressure was 110/70, his heart rate 40-50 bpm and irregular. An ECG revealed atrial fibrillation with a second degree of AV block. Ventricular rate did not exceed 45 bpm and an IV atropine injection was without effect. A transvenous pacing catheter was inserted, with ventricular pacing instituted at 60 bpm. Which of the following statements best explains the most likely reason for the patient's slow ventricular rate?

Digoxin induced stimulation of vagal nucleus

Digoxin induced compensation of cardiac insufficiency

Direct depressant effect of digoxin on vasomotor center

Direct depressant effect of digoxin upon SA and AV node

Digoxin induced appearance of a ventricular pacemaker

The correct answer is "Direct depressant effect of digoxin upon SA and AV node." Digoxin is a cardiac glycoside that is commonly used in the treatment of heart failure and atrial fibrillation. It works by inhibiting the sodium-potassium ATPase pump, leading to an increase in intracellular calcium levels and enhanced contractility of the heart. However, one of the side effects of digoxin is its direct depressant effect on the SA (sinoatrial) and AV (atrioventricular) nodes, which can result in a slow ventricular rate. In this case, the patient's slow heart rate, atrial fibrillation, and AV block are consistent with the direct depressant effect of digoxin on the SA and AV nodes.

Explanation

The correct answer is "Direct depressant effect of digoxin upon SA and AV node." Digoxin is a cardiac glycoside that is commonly used in the treatment of heart failure and atrial fibrillation. It works by inhibiting the sodium-potassium ATPase pump, leading to an increase in intracellular calcium levels and enhanced contractility of the heart. However, one of the side effects of digoxin is its direct depressant effect on the SA (sinoatrial) and AV (atrioventricular) nodes, which can result in a slow ventricular rate. In this case, the patient's slow heart rate, atrial fibrillation, and AV block are consistent with the direct depressant effect of digoxin on the SA and AV nodes.

8. 58-year-old woman with a history of congestive heart failure was admitted to the hospital because of an acute attack of angle closure glaucoma. The patient had been suffering from heart failure for two years. An emergency therapy was started. Which of the following drugs would be absolutely contraindicated in this patient?

Hydrochlorothiazide

Furosemide

Amiloride

Mannitol

Mannitol is a diuretic used to reduce intracranial pressure and intraocular pressure. However, it is contraindicated in patients with congestive heart failure because it can exacerbate fluid overload and worsen heart failure symptoms. Therefore, in this patient with a history of congestive heart failure, mannitol would be absolutely contraindicated.

Explanation

Mannitol is a diuretic used to reduce intracranial pressure and intraocular pressure. However, it is contraindicated in patients with congestive heart failure because it can exacerbate fluid overload and worsen heart failure symptoms. Therefore, in this patient with a history of congestive heart failure, mannitol would be absolutely contraindicated.

9. A 52-year-old man was admitted to the coronary unit with an acute myocardial infarction. Vital signs on admission were: blood pressure 98/50, heart rate 122 bpm, respiration 16 breaths/min. Exams showed a cardiac output of 2.9 L/min and a cardiac index 1.6 (normal, 2.5-4.2). An IV infusion of an inotropic drug was started. Which of the following was the most likely molecular mechanism of action of the given drug?

Inhibition of phosphodiesterase

Inhibition of Ca++/Na+ exchanger

Inhibition of Na+/K+ ATPase

Activation of beta-1 receptors

The most likely molecular mechanism of action of the given drug is the activation of beta-1 receptors. Activation of beta-1 receptors leads to an increase in heart rate and contractility, which can help improve cardiac output in a patient with acute myocardial infarction. This can be especially beneficial in a patient with low blood pressure and a decreased cardiac index.

Explanation

The most likely molecular mechanism of action of the given drug is the activation of beta-1 receptors. Activation of beta-1 receptors leads to an increase in heart rate and contractility, which can help improve cardiac output in a patient with acute myocardial infarction. This can be especially beneficial in a patient with low blood pressure and a decreased cardiac index.