A new antiarrhythmic medication (drug A) is tested in a series of experiments that measure the flow of ions responsible for producing an action potential in cardiac muscle cells.  Ion flow is measured before and after the drug is administered, and the results are shown in the chart below (each colored line represents a different type of ion).

Drug A has an antiarrhythmic effect most similar to which of the following drugs?

A 60-year-old man with known coronary artery disease comes to the office due to exertional chest tightness for the last 6 months.  The symptoms occur when he walks more than 3 blocks, especially in cold weather.  The patient underwent coronary artery bypass graft surgery 3 years ago for progressive angina.  Past medical history also includes asthma, benign prostate hyperplasia, and peripheral artery disease.  The physician discusses adding isosorbide dinitrate to his current therapy but the patient is concerned about adverse effects.  Which of the following is most likely to occur in this patient with the add-on therapy?

A 45-year-old man comes to the hospital with acute onset of severe chest pain and diaphoresis.  The patient describes the pain as “squeezing,” different from any discomfort he has ever had.  He has a past medical history of hypertension, and his father underwent coronary artery bypass grafting at age 50.  The patient is diagnosed with acute ST-elevation myocardial infarction and undergoes an urgent coronary intervention with stent placement into the right coronary artery.  He is also started on high-intensity atorvastatin therapy, along with antiplatelet therapy and appropriate medications to control blood pressure.  Four weeks later, the patient’s total cholesterol level is 140 mg/dL, down from 200 mg/dL before discharge.  Which of the following has most likely increased as the result of the therapy?

A 48-year-old man comes to the office for a follow-up visit.  He was diagnosed with hypercholesterolemia 6 months ago and has been strictly following dietary and lifestyle modifications as advised.  The patient has no other medical problems.  He does not use tobacco, alcohol, or illicit drugs.  His father has diabetes mellitus and coronary artery disease.  The patient’s blood pressure is 126/70 mm Hg and BMI is 33.1 kg/m².  Physical examination is normal.  Laboratory studies show a current LDL level of 190 mg/dL.  Which of the following should be obtained before starting statin therapy in this patient?

A 24-year-old man comes to the emergency department due to the sudden onset of palpitations.  The patient says it feels like “my heart is racing.”  He had an episode similar to this a year ago that resolved spontaneously.  Blood pressure is 126/74 mm Hg and pulse is 164/min.  Rapid intravenous administration of a medication to this patient results in instantaneous resolution of the arrhythmia but is accompanied by short-lived flushing, burning in the chest, and shortness of breath.  Which of the following medications was used to treat this patient’s condition?

A 56-year-old woman presents to your office with chronic cough.  She says that the cough is dry and affects quality of her life significantly.  She denies chest pain, hemoptysis and shortness of breath.  Her past medical history is significant for long-standing hypertension, diabetes and myocardial infarction experienced two months ago.  She does not smoke or consume alcohol.  Her blood pressure is 130/70 mmHg and heart rate is 70/min.  Which of the following is the best next step in the management of this patient?

A 43-year-old woman comes to the office due to occasional chest discomfort over the past year.  She describes the pain as a midline pressure or squeezing sensation that lasts 10-15 minutes and is sometimes accompanied by sweating.  The patient has no history of hypertension or diabetes mellitus but is a smoker.  Ambulatory ECG monitoring shows transient ST-segment elevations in the anteroseptal leads during an episode of chest pain at night.  Coronary angiography reveals no atherosclerotic stenosis, but the administration of acetylcholine elicits similar chest pain and ECG changes.  Which of the following best explains the coronary intervention findings in this patient?

A 60-year-old man comes to the hospital with chest pain.  He has had intermittent, squeezing substernal pain over the last 3 days that is now sustained.  The patient has no associated palpitations, lightheadedness, or shortness of breath.  Medical history is notable for moderate chronic obstructive pulmonary disease with a recent admission for an exacerbation.  Blood pressure is 145/90 mm Hg and pulse is 93/min.  Oxygen saturation by pulse oximetry is 98% on room air.  Physical examination shows no heart murmurs, and lungs are clear to auscultation.  ECG shows sinus rhythm with 2-mm anterior ST segment elevation.  Cardiac troponin I levels are elevated.  Which of the following is the most appropriate treatment for this patient?

A 68-year-old man comes to the office due to several weeks of progressive exertional dyspnea and lower extremity edema.  Medical history is significant for non-Hodgkin lymphoma, which is in remission after chemotherapy 8 years ago.  Blood pressure is 126/76 mm Hg and pulse is 88/min.  Physical examination reveals bibasilar lung crackles and 1+ bilateral lower extremity edema.  Echocardiography shows biventricular dilation and a left ventricular ejection fraction of 35%.  Stress myocardial perfusion scan is negative for inducible ischemia.  After initial stabilization, long-term use of which of the following medications will most likely improve survival in this patient?

A 43-year-old man comes to the emergency department due to a 3-day history of persistent headaches.  The patient has a history of hypertension and has had poor medical follow-up.  Blood pressure is 224/115 mm Hg and pulse is 67/min.  He appears mildly confused during the physical examination, but no focal neurologic deficits are noted.  Funduscopic examination shows bilateral papilledema.  Serum creatinine is 1.4 mg/dL.  An intravenous medication is initiated that causes arteriolar dilation while also improving renal perfusion and increasing natriuresis.  Which of the following agents is most likely being used in this patient?

A 49-year-old woman is brought to the emergency department with squeezing chest pain and profuse sweating for the last 2 hours.  Medical history includes diet-controlled type 2 diabetes mellitus.  ECG reveals ST-segment elevation in leads I, aVL, and V1-V4.  The patient is immediately taken to the cardiac catheterization laboratory, where she is found to have complete occlusion of the left anterior descending coronary artery.  The blockage is opened with percutaneous coronary intervention with stenting, but afterward she experiences recurrent and sustained episodes of ventricular arrhythmia.  She is treated with an antiarrhythmic agent that preferentially binds to rapidly depolarizing and ischemic ventricular myocardial fibers and has minimal effect on normal ventricular myocardium.  Which of the following agents was most likely used in this patient?

A new drug has been developed to treat cardiac arrhythmias.  The drug has high affinity for activated and inactivated sodium channels but relatively little affinity for resting sodium channels.  An experiment is devised to maintain sodium channels in the inactivated state for a prolonged period, during which they are exposed to the new drug.  After allowing the sodium channels to return to the resting state, the speed of the drug’s dissociation from the sodium channels is recorded and shown below.  The dissociation curve for quinidine is given for comparison.

The pharmacologic action of the new drug is most similar to which of the following drugs?

A 49-year-old man comes to the emergency department with severe shortness of breath.  The patient has a history of hypertension and medication nonadherence.  Blood pressure is 260/144 mm Hg and pulse is 100/min.  Chest examination demonstrates bibasilar crackles.  There are no heart murmurs.  Serum creatinine is 1.6 mg/dL.  Intravenous furosemide and continuous nitroprusside infusion are started, along with noninvasive positive pressure ventilation, and he experiences improvement in his symptoms.  The next morning, the patient is confused and lethargic, and he suffers a generalized tonic-clonic seizure.  The skin appears flushed, and serum lactic acid level is elevated.  The nitroprusside infusion rate is found to be higher than recommended.  Which of the following mechanisms is most likely responsible for the drug toxicity seen in this patient?

A 57-year-old man is seen in the office after an episode of acute pancreatitis.  Hospital evaluation found no evidence of gallstones.  The patient does not consume alcohol, but he does have a history of severe hypertriglyceridemia.  He was treated with a fibrate medication in the past but could not tolerate it due to liver toxicity.  He has no history of diabetes mellitus or hypertension.  On examination, the patient has no abdominal tenderness.  Laboratory studies show normal hepatic and pancreatic enzyme levels, but the patient again has a severely elevated triglyceride level.  The physician prescribes the appropriate medications and explains that the patient is likely to experience skin flushing and warmth after taking the pills.  Which of the following is the primary agent mediating these side effects?

A 55-year-old man comes to the office for follow-up of hypertension and coronary heart disease.  He has been on several medications in the past with suboptimal blood pressure control.  The physician considers adding verapamil to the patient’s current regimen, as its vasodilatory properties make it useful for controlling systemic hypertension.  Verapamil also affects cardiac contractility but has a minimal effect on skeletal muscle.  Which of the following properties of skeletal muscle is responsible for its resistance to the medication?

A 66-year-old man comes to the office for a follow-up appointment.  The patient has a history of heart failure with reduced ejection fraction and has had persistent dyspnea despite taking the maximal dosage of his heart failure medications.  He has had no lightheadedness or chest pain.  Blood pressure is 133/72 mm Hg and pulse is 76/min.  Physical examination shows normal lung sounds and no lower extremity edema.  His medical treatment is modified with the addition of a combination pill that inhibits neprilysin and blocks angiotensin II receptors.  Which of the following is the most likely effect of this medication?

A 43-year-old man is being evaluated for occasional retrosternal chest pressure that develops with moderate exertion and sometimes occurs when resting.  He does not use alcohol, tobacco, or illicit drugs.  The patient has an extensive family history of coronary artery disease.  His temperature is 36.7 C (98 F), blood pressure is 124/72 mm Hg, pulse is 81/min, and respirations are 14/min.  Physical examination shows no abnormalities.  Coronary angiography shows mild luminal irregularities but no significant obstructive lesions.  Acetylcholine infusion during the procedure results in dilation of epicardial coronary vessels.  A reaction involving which of the following amino acids is most likely responsible for the observed dilation?

Researchers are observing how coronary blood flow changes in response to progressive increases in the mean arterial blood pressure (see graph below).

The mostly horizontal portion of the slope indicates a region where coronary blood flow is relatively insensitive to blood pressure changes.  Within this zone of autoregulation, the metabolic demands of the myocardium are the main determinant of coronary blood flow.  Which of the following endogenous factors is most responsible for controlling coronary blood flow within this range?

A 63-year-old man comes to the emergency department due to dyspnea.  Over the past several days, the patient has experienced progressively worsening shortness of breath while walking his dog around the block.  In addition, he could not breathe while lying in bed last night and fell asleep only after moving to a recliner.  The patient had an acute myocardial infarction 2 years ago and has been nonadherent with his medications and follow-up appointments.  Temperature is 36.7 C (98 F), blood pressure is 122/74 mm Hg, pulse is 94/min, and respirations are 22/min.  Physical examination shows bibasilar lung crackles, jugular venous distension, and bilateral pitting edema in the lower extremities.  Chest x-ray reveals cardiomegaly and pulmonary venous congestion.  Which of the following factors is most likely contributing to this patient’s symptoms?

A 62-year-old man is hospitalized for chest pain and palpitations.  His past medical history is significant for coronary artery disease, ischemic cardiomyopathy, paroxysmal atrial fibrillation, and hypertension.  Blood pressure on admission is 135/78 mm Hg and pulse is 78/min.  During hospitalization, the patient has 2 episodes of brief loss of consciousness.  ECG recording during the episodes shows polymorphic QRS complexes that change in amplitude and cycle length.  Between the episodes, his ECG shows QT interval prolongation but is otherwise unremarkable.  Which of the following medications is most likely responsible for this patient’s condition?

A 54-year-old man is transferred to the hospital from his cardiologist’s office due to atrial fibrillation with rapid ventricular response.  His symptoms began 24 hours earlier with palpitations, lightheadedness, and chest tightness.  The patient has had similar episodes several times during the last year.  Past history is notable for mitral valve repair 3 years ago for severe symptomatic mitral regurgitation.  The patient undergoes direct current cardioversion due to worsening hemodynamic instability, with resolution of the arrhythmia and all associated symptoms.  He is considered for long-term amiodarone therapy to prevent future arrhythmic episodes.  Which of the following should be tested before initiating this medication?

A 46-year-old man is diagnosed with resistant hypertension.  He had a comprehensive workup for secondary hypertension, which was unrevealing.  The patient has tried multiple antihypertensive medications without significant effect.  Past medical history is otherwise unremarkable.  He agrees to enroll in a trial of a new long-acting medication that causes selective direct relaxation of the smooth muscle of arterioles but does not affect the veins.  Which of the following adverse effects is most likely to be caused by the drug during the clinical trial?

A 45-year-old man comes to the emergency department due to shortness of breath and fatigue that has progressed over the last 2 weeks.  The patient was diagnosed with nonischemic cardiomyopathy 2 years ago and has not been adherent with physician visits and his medical regimen.  Blood pressure is 106/58 mm Hg, and pulse is 88/min and regular.  The patient appears uncomfortable when lying flat.  Jugular venous pressure is elevated.  Bibasilar crackles are heard on lung auscultation and an S3 is present.  There is 1+ bilateral lower extremity pitting edema.  Milrinone infusion is initiated.  Which of the following is the most likely response to this therapy?

A 76-year-old woman is brought to the emergency department by her son due to lethargy and confusion over the past 2 days.  The patient has persistent atrial fibrillation and congestive heart failure and is on multiple medications.  Recently, she has had nausea and decreased appetite.  Today, she had 3 episodes of vomiting.  The patient also reports vision difficulties.  Temperature is 36.7 C (98 F) and blood pressure is 133/80 mm Hg.  Laboratory results are as follows:

ECG shows junctional escape rhythm at a rate of 48/min with occasional ventricular premature beats.  Increased blood level of which of the following medications is most likely responsible for her symptoms?

A 65-year-old man comes to the physician after missing a follow-up appointment for congestive heart failure.  He missed his appointment due to an upset stomach that will not go away.  A detailed history reveals disturbed color perception, anorexia, nausea, vomiting, and diarrhea that have worsened over the past 2 weeks.  His congestive heart failure has thus far been controlled effectively with multiple medications.  If the cause of this patient’s current symptoms is not corrected, which of the following complications is most likely to develop?

A 77-year-old man comes to the office after he was found to have high blood pressure during a health fair.  The patient denies any medical problems and feels proud that he has not needed to see a doctor for many years.  His blood pressure is 170/70 mm Hg and pulse is 74/min.  Other physical examination findings are normal.  The patient is started on a medication to treat his hypertension.  During his follow-up visit 3 weeks later, he reports bilateral leg swelling.  He has no chest pain, shortness of breath, or abdominal symptoms.  His blood pressure is 135/65 mm Hg and pulse is 80/min.  Cardiopulmonary examination is normal, but there is bilateral, symmetrical, 2+ pitting lower extremity edema.  Laboratory studies show serum creatinine of 0.8 mg/dL, and urinalysis is negative for proteinuria.  Which of the following was most likely prescribed to treat this patient’s hypertension?

A 25-year-old man comes to the office due to shortness of breath.  He states that even moderate exertion forces him to stop to catch his breath.  The patient has no family history of sudden cardiac death.  He does not use tobacco or illicit drugs.  On examination, the patient has a faint systolic murmur at the left sternal border in the supine position that increases to 3/6 in intensity with Valsalva maneuver.  Echocardiography shows interventricular septal hypertrophy and increased left ventricular mass.  The patient is started on high-dose beta blocker therapy.  On follow-up 2 weeks later, he reports significant improvement in his shortness of breath.  Physical examination reveals no murmurs supine or with Valsalva.  Which of the following best accounts for improvement of this patient’s symptoms?

A 23-year-old man comes to the office due to chest discomfort that usually occurs during exercise, such as jogging or climbing stairs.  The symptoms go away 5 to 10 minutes after he stops.  The patient has not had syncope but mentions some shortness of breath that accompanies the chest pain.  Family history includes an uncle who died suddenly at age 35.  Blood pressure is 122/70 mm Hg and pulse is 70/min and regular.  The apical impulse is strong and sustained.  While supine, the patient has a soft crescendo-decrescendo systolic murmur at the apex and left sternal border; it becomes quite pronounced when he stands.  Which of the following medications should be avoided while treating this patient’s condition?

A 45-year-old man who was recently started on medication for paroxysmal atrial fibrillation undergoes stress ECG testing.  The patient exercises on a treadmill for 9 minutes and reaches 98% of age-predicted maximal heart rate without chest pain or ST-segment changes.  His pre-test resting QRS complex duration is 95 msec (normal: 80-120 msec) and corrected QT (QTc) interval duration is 410 msec (normal <440 msec).  ECG findings recorded at his maximally achieved heart rate show a QRS complex duration of 125 msec and QTc interval duration of 400 msec.  Based on the patient’s test results, which of the following medications is most likely being used to treat his atrial fibrillation?

A 58-year-old man comes to the office due to progressive fatigue, dyspnea on exertion, and orthopnea.  Medical history is significant for hypertension, hyperlipidemia, and a myocardial infarction 2 years ago.  The patient says he has not taken his medications in several months because he was “feeling well.”  Blood pressure is 160/95 mm Hg and pulse is 94/min and regular.  Physical examination shows bilateral lung crackles and lower extremity edema.  The point of maximal impulse is displaced toward the axilla, and an S3 is heard.  Serum creatinine is 0.9 mg/dL and serum potassium is 4.2 mEq/L.  After this patient’s condition has stabilized, long-term use of which of the following medications will most likely reduce mortality?

A 53-year-old man comes to the emergency department with shortness of breath and chest tightness.  The patient was playing in a poker tournament when his symptoms first began.  He has a history of hypertension and is not compliant with his medications.  His last medical follow-up was a year ago.  Blood pressure is 195/115 mm Hg and pulse is 90/min and regular.  Lung examination reveals bibasilar crackles.  Nitroglycerin infusion is started and results in significant symptomatic improvement.  Repeat blood pressure is 165/90 mm Hg.  Which of the following intracellular events is most likely responsible for the beneficial effects of this patient’s treatment?

A 68-year-old man comes to the office with a 6-week history of muscle pain and fatigue.  He has achy pain that is not related to activity.  The patient has tried warm compresses and over-the-counter analgesics without relief.  Past medical history is significant for hypertension, mixed hyperlipidemia, and coronary artery disease with an acute myocardial infarction 2 years ago.  Physical examination shows diffuse tenderness in the proximal muscles of the upper and lower extremities.  Serum creatine kinase activity is elevated.  Which of the following drug combinations is most likely responsible for this patient’s condition?

A 34-year-old woman has recurrent throbbing headaches that occur several times a month and cause significant distress.  They are accompanied by nausea and photophobia.  She has had 5 emergency department visits for these headaches over the last 6 months.  During office visits, her blood pressure ranges from 140/90 mm Hg to 150/95 mm Hg.  Neurologic examination is unremarkable.  The patient is prescribed metoprolol and is advised that the medication is expected to decrease the frequency of headaches and also lower blood pressure in the long term.  Which of the following best explains this medication’s effect on blood pressure?

A 50-year-old man has recurrent episodes of paroxysmal atrial fibrillation accompanied by uncomfortable palpitations and chest pressure.  Echocardiogram reveals normal biventricular function and no significant valvular disease.  Coronary angiography reveals no obstructive coronary artery disease.  The patient is started on medication to reduce his symptoms.  Two weeks later, he is seen in the emergency department for lightheadedness, weakness, and presyncope.  ECG reveals sinus bradycardia at a rate of 53/min with QTc prolongation (508 msec).  Telemetry monitoring reveals a short episode of self-resolved torsades de pointes.  Which of the following medications was most likely used to treat this patient’s palpitations?

A 37-year-old man with no significant medical history comes to the office due to intermittent palpitations.  He has a healthy lifestyle, exercises daily, and does not use tobacco, alcohol, or illicit drugs.  ECG shows atrial fibrillation with rapid ventricular response.  Echocardiogram reveals normal heart function with no significant valvular disease.  The patient is started on an antiarrhythmic medication that is known to be effective against both atrial and ventricular arrhythmias.  On ECG, this medication causes QRS prolongation with only minimal increase in QT interval duration.  Which of the following regions of the action potential curve is most affected by this drug?

A 55-year-old man comes to the emergency department with recurrent episodes of retrosternal chest pain.  The episodes occur during physical activity, usually when he climbs stairs or walks uphill.  The patient has no known medical problems and does not use tobacco, alcohol, or illicit drugs.  He is given a sublingual tablet and reports rapid relief of the pain.  This drug most likely improved this patient’s symptoms by causing which of the following hemodynamic changes?

A 69-year-old man comes to the office due to a 6-month history of chest tightness when he walks uphill or climbs stairs.  The discomfort radiates to his throat and lasts 5-10 minutes before slowly subsiding.  Medical history is significant for hyperlipidemia and type 2 diabetes mellitus.  His father had coronary artery bypass surgery at age 60 and his mother suffered a stroke.  Vital signs are normal.  Cardiac examination reveals no murmurs or additional heart sounds.  The patient is prescribed a medication that is metabolized to S-nitrosothiols in the vascular smooth muscle cells, and he reports rapid and significant symptom relief.  Which of the following components of the cardiovascular system is most susceptible to the medication prescribed to this patient?