questions 11

Antianginal Therapy

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Topic updated on 06/23/17 4:37pm

Introduction
  • Symptoms of angina due to ischemia = myocardial oxygen demand exceeds supply
  • Goal is to ↓ myocardial O2 consumption (MVO2)
    • can achieve by reducing:
      • end diastolic volume (preload)
      • blood pressure
      • heart rate
      • contractility
      • ejection time
  • Can also ↑ O2 supply to myocardium
  • Main drugs include nitrates, beta-blockers, and calcium channel blockers
Nitrates
  • Examples
    • nitroglycerin, isosorbide dinitrate (also mononitrate), and nitroprusside 
  • Mechanism 
    • venodilation via generation of endothelial NO   
      • results in activation of guanylyl cyclase → ↑cGMP→ relaxation of smooth muscle   
      • dilate veins >> arteries 
    • ↓ EDV and ↓ BP → ↓ MVO2
    • reflex ↑ in contractility and HR
    • isosorbide mononitrate has highest oral bioavailability
  • Clinical use
    • angina  
    • pulmonary edema
    • aphrodisiac and erection enhancer
  • Toxicity
    • orthostatic hypotension
    • headache
      • due to vasodilation of cerebral arteries 
    • reflex tachycardia
    • tachyphylaxis
    • contraindicated in patients taking vasodilatory medication for erectile dysfunction (e.g. sildenafil)
      • severe hypotension
    • nitroprusside causes cyanide toxicity 
    • "Monday disease" seen in individuals with industrial exposure
      • development of tolerance for the vasodilating action during the work week 
      • loss of tolerance over the weekend
      • results in tachycardia, dizziness, headache on re-exposure
  • 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 
Beta-Blockers
  • Examples
    • propranolol, atenolol, and metoprolol
  • Mechanism
    • β-adrenergic antagonism 
      • results in ↓ cAMP
    • ↓ contractility, HR, and BP→ ↓ MVO2
  • Toxicity
    • impotence, depression, and bradycardia
    • pindolol and acebutolol are partial β-agonists
      • contraindicated in angina
Calcium Channel Blockers
  • Examples
    • nifedipine, verapamil, and diltiazem
  • Mechanism
    • ↓ vascular smooth muscle contractility  
      • result of inhibition of voltage-gated L-type Ca2+ channels
      • also affects cardiac tissue
      • nifedipine is most selective for vasculature
      • verapamil is most selective for heart
        • "Verapamil works on Ventricles"
    • ↓ afterload and ↓ AV node conduction velocity → ↓ MVO2
  • Clinical use
    • angina
    • hypertension
    • arrhythmias (not nifedipine) (see Antiarrhythmics)
    • vasospasm
      • Prinzmetal's angina
      • Raynaud's
  • Toxicity
    • cardiac depression
    • peripheral edema
    • AV block
    • headache
    • flushing
    • dizziness
    • constipation


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Qbank (7 Questions)

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

1. Transient ischemic attack
2. Elevated creatine kinase
3. Beta adrenergic inactivation
4. Acute hemorrhage
5. Vasodilation of cerebral arteries

PREFERRED RESPONSE ▶
TAG
(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? Topic Review Topic

1. Large arteries
2. Large veins
3. Arterioles
4. Cardiac muscle
5. Pulmonary arteries

PREFERRED RESPONSE ▶
TAG
(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? Topic Review Topic

1. Oral
2. Sublingual
3. Intramuscular injection
4. Intravenous injection
5. Subcutaneous injection

PREFERRED RESPONSE ▶
TAG
(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? Topic Review Topic

1. Decreased cardiac contractility
2. Increased left ventricular end-diastolic pressure
3. Decreased stroke volume
4. Decreased pulmonary capillary wedge pressure
5. Increased systemic vascular resistance

PREFERRED RESPONSE ▶
TAG
(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? Topic Review Topic

1. Gout
2. Erectile dysfunction
3. Arthritis
4. Mitral stenosis
5. Diabetic peripheral neuropathy

PREFERRED RESPONSE ▶
TAG
(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? Topic Review Topic

1. Transdermal nitroglycerin patch placed at 7AM then removed and replaced with another at 7PM
2. PO regular-release isosorbide dinitrate taken at 8AM, noon, and 5PM
3. Transdermal nitroglycerin patch placed at bedtime and removed at 7AM without replacement
4. Transdermal nitroglycerin patch placed upon awakening in the morning and removed at 7PM without replacement
5. PO extended release isosorbide-5-mononitrate once daily at 8AM

PREFERRED RESPONSE ▶
TAG
(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? Topic Review Topic

1. Increased cAMP; Increased cAMP
2. Increased contractility; Decreased endothelial nitrous oxide
3. Decreased cAMP; Increased cGMP
4. Decreased cGMP; Increased venous resistance
5. Increased heart rate; Decreased arterial resistance

PREFERRED RESPONSE ▶
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