Updated: 4/3/2018

Antianginal Therapy

Topic
Review Topic
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Questions
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Evidence
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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 (10)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8 - 20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: <= 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, toal, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70 - 110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time (template) 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm^3
Female: 3.5-5.5 million mm^3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c <=6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm^3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm^3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm^3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm^3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m^2
Calculator

(M1.CV.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? Review Topic

QID: 100649
1

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

41%

(7/17)

2

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

18%

(3/17)

3

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

24%

(4/17)

4

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

12%

(2/17)

5

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

6%

(1/17)

M1

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PREFERRED RESPONSE 1

(M1.CV.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? Review Topic

QID: 100612
1

Decreased cardiac contractility

25%

(2/8)

2

Increased left ventricular end-diastolic pressure

0%

(0/8)

3

Decreased stroke volume

50%

(4/8)

4

Decreased pulmonary capillary wedge pressure

25%

(2/8)

5

Increased systemic vascular resistance

0%

(0/8)

M1

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PREFERRED RESPONSE 4

(M1.CV.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? Review Topic

QID: 100531
1

Large arteries

7%

(10/141)

2

Large veins

70%

(99/141)

3

Arterioles

19%

(27/141)

4

Cardiac muscle

2%

(3/141)

5

Pulmonary arteries

0%

(0/141)

M1

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PREFERRED RESPONSE 2

(M1.CV.14) A 62-year-old Caucasian male receiving treatment for stable angina experiences intermittent throbbing headaches. What is the most likely cause? Review Topic

QID: 100530
1

Transient ischemic attack

9%

(18/205)

2

Elevated creatine kinase

1%

(3/205)

3

Beta adrenergic inactivation

2%

(4/205)

4

Acute hemorrhage

1%

(2/205)

5

Vasodilation of cerebral arteries

86%

(176/205)

M1

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PREFERRED RESPONSE 5
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(M1.CV.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? Review Topic

QID: 106996
1

Increased cAMP; Increased cAMP

9%

(9/105)

2

Increased contractility; Decreased endothelial nitrous oxide

3%

(3/105)

3

Decreased cAMP; Increased cGMP

75%

(79/105)

4

Decreased cGMP; Increased venous resistance

5%

(5/105)

5

Increased heart rate; Decreased arterial resistance

8%

(8/105)

M1

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PREFERRED RESPONSE 3
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(M1.CV.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? Review Topic

QID: 100538
1

Oral

0%

(0/12)

2

Sublingual

92%

(11/12)

3

Intramuscular injection

0%

(0/12)

4

Intravenous injection

0%

(0/12)

5

Subcutaneous injection

0%

(0/12)

M1

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PREFERRED RESPONSE 2

(M1.CV.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? Review Topic

QID: 100616
1

Gout

0%

(0/12)

2

Erectile dysfunction

83%

(10/12)

3

Arthritis

0%

(0/12)

4

Mitral stenosis

17%

(2/12)

5

Diabetic peripheral neuropathy

0%

(0/12)

M1

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PREFERRED RESPONSE 2
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