Updated: 10/11/2020

Antianginal Therapy

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Snapshot
  • A 50-year-old man presents to the emergency department after experiencing chest pain. He describes the pain as pressure-like that affects the sternum and radiates down the left arm. Medical history is significant for hypertension, hypercholesterolemia, and type II diabetes. He smokes 1 pack of cigarettes per day for the past 20 years. On physical exam, the patient appears anxious and diaphoretic. An electrocardiogram demonstrates an ST-segment elevation in leads V1 and V2. Cardiac troponins are sent. He is given aspirin, nitroglycerin, metoprolol, clopidogrel, and unfractionated heparin. The cardiac catheterization lab is activated and the cardiologist is consulted.
Introduction
  • Appropriate treatment for acute coronary syndrome must be instituted immediately in order to
    • limit myocardial damage
    • decrease the risk of complications
    • restore the balance between myocardial oxygen supply and demand
NSTEMI and Unstable Angina (UA)
  • Introduction
    • NSTEMI and UA are managed in the same manner
    • the goal is to to provide 
      • anti-ischemic therapy
        • restores the myocardial oxygen supply and demand
      • anti-thrombotic therapy
        • prevents further growth of the partial thrombotic occlusion
  • Medications
    • anti-ischemic therapy
      • β-blockers (e.g., metoprolol)
        • mechanism
          • decreased sympathetic drive to the heart
            • promotes myocardial electrical stability
            • decreases myocardial demand
            • ↓ cAMP 
          • improves mortality in patients with an MI
        • contraindications
          • bronchospasm
          • decompensated heart failure
          • hypotension
      • nitrates (e.g., nitroglycerin, isosorbide mononitrate, and dinitrate)  
        • mechanism 
          • venodilation reduces preload to the heart, which reduces myocardial demand
            • recall that a reduction in preload reduces ventricular wall stress
          • coronary artery dilation improves blood flow to the myocardium
            • recall that venodilation >> arterial dilation 
          • ↑ cGMP 
          • arginine is a biochemical precursor of nitric oxide, and supplementation of this amino acid may have a role in augmenting the treatment regimen for chronic stable angina patients  
          • contraindicated in patients taking vasodilatory medication for erectile dysfunction (e.g., sildenafil)  
        • adverse events
          • nitroprusside causes cyanide toxicity 
          • development of tolerance for the vasodilating action during the work week 
          • a headache may result from vasodilation of cerebral arteries  
      • calcium channel blockers (e.g., verapamil and diltiazem)
        • mechanism
          • reduces heart rate and cardiac contractility
          • this medication is reserved for patients unresponsive to β-blockers and nitrates or have contraindications to β-blockers
            • this is because calcium channel blockers do not provide a mortality benefit
    • anti-thrombotic therapy
      • aspirin
        • mechanism
          • an inhibitor of thromboxane A2 synthesis 
            • thromboxane A2 is a prominent promoter of platelet activation
          • improves mortality and should be continued indefinitely
      •  P2Y12 ADP receptor inhibitor (e.g., clopidogrel and ticagrelor)
        • mechanism
          • prevents ADP from binding to the P2Y12 receptor, which would normally further activate platelets
    • anti-coagulation therapy
      • unfractionated heparin
        • mechanism
          • binds to antithrombin to enhance its effects
          • inhibits factor Xa
ST-Segment Elevation Myocardial Infarction (STEMI)
  • Introduction
    • STEMI suggest that there is a total occlusion of the vessel
      • thus the main goal is to induce rapid reperfusion via
        • percutaneous coronary intervention (PCI) OR
        • fibrinolytic therapy
      • patients are also given medications such as those used in NSTEMI and UA
        • aspirin
        • unfractionated heparin
        • β-blockers
        • nitrates
        • P2Y12 ADP receptor inhibitor 
  • Reperfusion therapy
    • primary PCI 
      • the preferred method for reperfusion
      • must be performed within 90 minutes of first medical contact
        • aspirin and a P2Y12 receptor inhibitor is given prior to the procedure
    • fibrinolytic therapy (e.g., alteplase)
      • performed if PCI cannot be performed within 90 minutes or is unavailable
      • fibrinolytics convert plasminogen to plasmin, which degrades newly formed clots
Adjunctive Therapy
  • Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril)
    • provides a mortality benefit
    • prevents ventricular cardiac remodeling and reduces the rate of heart failure
  • Statins (e.g., atorvastatin) 
    • an HMG-CoA reductase inhibitor that lowers cholesterol levels

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Questions (11)
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(M1.CV.15.4196) A 73-year-old man presents to his primary care physician with chest pain. He noticed the pain after walking several blocks, and the pain is relieved by sitting. On exam, he has a BP 155/89 mmHg, HR 79 bpm, and T 98.9 F. The physician refers the patient to a cardiologist and offers prescriptions for carvedilol and nitroglycerin. Which of the following describes the mechanism or effects of each of these medications, respectively? Tested Concept

QID: 106996
1

Increased cAMP; Increased cAMP

7%

(16/222)

2

Increased contractility; Decreased endothelial nitrous oxide

2%

(4/222)

3

Decreased cAMP; Increased cGMP

82%

(181/222)

4

Decreased cGMP; Increased venous resistance

4%

(9/222)

5

Increased heart rate; Decreased arterial resistance

5%

(11/222)

M 3 D

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(M1.CV.13.133) A 55-year-old male is started on nitrate therapy for treatment of stable angina. He experiences significant and immediate relief of his symptoms within minutes of starting therapy. Approximately 48 hours after initiating this new medication, he notes return of chest pain and pressure with exertion that no longer responds to continued nitrate use. Which of the following 24-hour dosing schedules would most likely explain this patient's response to nitrate treatment? Tested Concept

QID: 100649
1

Transdermal nitroglycerin patch placed at 7AM then removed and replaced with another at 7PM

34%

(42/124)

2

PO regular-release isosorbide dinitrate taken at 8AM, noon, and 5PM

16%

(20/124)

3

Transdermal nitroglycerin patch placed at bedtime and removed at 7AM without replacement

19%

(24/124)

4

Transdermal nitroglycerin patch placed upon awakening in the morning and removed at 7PM without replacement

15%

(18/124)

5

PO extended release isosorbide-5-mononitrate once daily at 8AM

13%

(16/124)

M 3 E

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(M1.CV.13.96) A 58-year-old male presents with an acutely elevated blood pressure of 220/140 mmHg. The patient complains of a headache and chest pain, and he has been vomiting for the last several hours. Physical exam demonstrates papilledema and a depressed level of consciousness. To treat this patient's hypertensive emergency, he is started on an IV medication commonly used in this situation. The agent exerts its effect by releasing nitric oxide as a metabolite, which subsequently activates guanylate cyclase and increases production of cGMP in vascular smooth muscle. Which of the following clinical effects would be expected from administration of this medication? Tested Concept

QID: 100612
1

Decreased cardiac contractility

7%

(8/110)

2

Increased left ventricular end-diastolic pressure

5%

(5/110)

3

Decreased stroke volume

40%

(44/110)

4

Decreased pulmonary capillary wedge pressure

47%

(52/110)

5

Increased systemic vascular resistance

1%

(1/110)

M 1 E

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(M1.CV.13.100) A 66-year-old gentleman presents to a new primary care physician to establish care after a recent relocation. His past medical history is significant for gout, erectile dysfunction, osteoarthritis of bilateral knees, mitral stenosis, and diabetic peripheral neuropathy. He denies any past surgeries along with the use of any tobacco, alcohol, or illicit drugs. He has no known drug allergies and cannot remember the names of the medications he is taking for his medical problems. He states that he has recently been experiencing chest pain with strenuous activities. What part of the patient's medical history must be further probed before starting him on a nitrate for chest pain? Tested Concept

QID: 100616
1

Gout

3%

(3/90)

2

Erectile dysfunction

81%

(73/90)

3

Arthritis

1%

(1/90)

4

Mitral stenosis

10%

(9/90)

5

Diabetic peripheral neuropathy

1%

(1/90)

M 1 E

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(M1.CV.12.15) A 56-year-old man with substernal chest pain calls 911. When paramedics arrive, they administer drug X sublingually for the immediate relief of angina. What is the most likely site of action of drug X? Tested Concept

QID: 100531
1

Large arteries

6%

(15/268)

2

Large veins

70%

(188/268)

3

Arterioles

21%

(57/268)

4

Cardiac muscle

2%

(6/268)

5

Pulmonary arteries

0%

(0/268)

M 1 E

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(M1.CV.12.14) A 62-year-old Caucasian male receiving treatment for stable angina experiences intermittent throbbing headaches. What is the most likely cause? Tested Concept

QID: 100530
1

Transient ischemic attack

7%

(23/318)

2

Elevated creatine kinase

1%

(4/318)

3

Beta adrenergic inactivation

3%

(9/318)

4

Acute hemorrhage

1%

(2/318)

5

Vasodilation of cerebral arteries

87%

(277/318)

M 2 E

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(M1.CV.12.22) A 45-year-old Caucasian man is given nitroglycerin for the management of his stable angina. Nitroglycerin given for the rapid relief of acute angina would most likely be given through what route of administration? Tested Concept

QID: 100538
1

Oral

1%

(1/100)

2

Sublingual

96%

(96/100)

3

Intramuscular injection

0%

(0/100)

4

Intravenous injection

2%

(2/100)

5

Subcutaneous injection

0%

(0/100)

M 3 E

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Evidence (12)
EXPERT COMMENTS (22)
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