3.1 Nitrates & Antianginals

Nitrates & Antianginals CVTT 1110

Page 1: Introduction

• Overview of Nitrates and Antianginals in the context of cardiovascular health.

Page 2: Objectives

• Understanding Angina

• Mechanisms of Nitrates

• Metabolic Antianginals

Page 3: Effort Angina

• Ischemic Symptoms Cascade

  • Pain relief and ECG normalization

  • Symptoms include dyspnea and systolic dysfunction

  • Recovery time varies from seconds to hours after exertion stops.

Page 4: Types of Angina

• Stable Angina

• Unstable Angina

• Prinzmetal Angina

• Syndrome X

Page 5: Stable Angina

• Characteristics

  • Predictable and induced by exertion or exercise.

  • Caused by atherosclerosis.

  • Relieved by rest or nitroglycerin.

Page 6: Unstable Angina

• Characteristics

  • Caused by ruptured coronary artery plaque (Acute Coronary Syndrome - ACS).

  • Unpredictable with increased frequency, intensity, and duration.

  • Occurs at rest or during activity and is not relieved by rest or nitroglycerin.

Page 7: Prinzmetal Angina

• Characteristics

  • Variant or vasospastic angina caused by coronary vasospasm.

  • Occurs spontaneously at rest, often at night or early morning.

  • Associated with transient ST-segment elevation and can lead to myocardial infarction (MI) or arrhythmias.

Page 8: Syndrome X

• Characteristics

  • Formerly known as microvascular angina.

  • Presents as typical exertional angina with a positive exercise stress test.

  • Visually normal coronary arteries but caused by microvascular dysfunction.

Page 9: Angina Pathophysiology

• Oxygen Demand vs. Supply

  • Decreased blood flow due to vasospasm, stenosis, or thrombosis leads to angina.

  • Increased oxygen consumption due to elevated heart rate, contractility, afterload, and preload.

Page 10: Classes of Antianginals

• Beta Blockers (BBs)

  • Negative heart rate and inotropic effects.

• Calcium Channel Blockers (CCBs)

  • Vasodilators that reduce preload.

• Metabolic Antianginals

  • New class with metabolic modulation without major hemodynamic effects.

• Nitrates

  • Vasodilators.

Page 11: Nitrates Mechanism

• Venodilator Effects

  • Decrease preload, ventricular chamber size, and fiber tension.

  • At higher doses, they act as arterial vasodilators, decreasing afterload and increasing blood flow to ischemic areas.

Page 12: Nitrates and Oxygen Supply

• Mechanism of Action

  • Dilation of large epicardial coronary arteries and peripheral vessels.

  • Low doses primarily affect preload; high doses affect afterload.

Page 13: Systemic Effects of Nitrates

• Action on Circulation

  • Dilate arterioles and ischemic venous zones, reducing venous return and afterload.

Page 14: Nitric Oxide (NO)

• Role in Vasodilation

  • Short-lived free radical that aids in vessel constriction and dilation.

  • Levels decrease with age and progression of coronary artery disease (CAD).

Page 15: Nitrates Administration

• Absorption and Half-life

  • Absorbed through mucous membranes, skin, and GI tract.

  • Long-acting nitrates require a 10-hour nitro-free period to prevent tolerance.

• Routes of Administration

  • Sublingual (SL), tablets, spray, transdermal patches, and oral pills.

Page 16: Short-Acting vs. Long-Acting Nitrates

• Short-Acting Nitrates

  • SL NTG: 0.3 – 0.6 mg every 5 minutes for relief; onset 1-2 minutes.

• Long-Acting Nitrates

  • Isosorbide Dinitrate: SL/PO with varying durations of relief.

Page 17: Long-Acting Nitrates Administration

• Dosing Strategies

  • Monoket/Ismo: BID with 7 hours between doses.

  • Imdur: QID with time-released formulations.

Page 18: Nitrates Interactions

• Contraindications

  • Use with phosphodiesterase-5 inhibitors (e.g., Vardenafil, Tadalafil, Sildenafil) can lead to severe hypotension.

Page 19: Nitrates Side Effects & Contraindications

• Common Side Effects

  • Hypotension, headache, methemoglobinemia, syncope, tachycardia.

• Contraindications

  • Hypertrophic obstructive cardiomyopathy (HOCM), use of sildenafil, cor pulmonale, right ventricular myocardial infarction (RVMI).

Page 20: Nitrates for Acute Coronary Syndrome (ACS)

• Usage Guidelines

  • Intravenous NTG for angina; contraindicated in systolic BP <90 mmHg.

Page 21: Metabolic Antianginal Agents

• Ranolazine (Ranexa)

  • Indicated for chronic effort angina; inhibits slow inward sodium current.

  • Potential benefits for atrial fibrillation and symptomatic status in systolic heart failure.

Page 22: Step-Care for Angina of Effort

• Therapeutic Approach

  • 1st Line: Short-acting nitrates with beta blockers or CCBs.

  • 2nd Line: Combination therapy with additional agents.

  • 3rd Line: Long-acting nitrates.

  • Overall care includes a full history and physical exam before treatment.

Page 23: Questions?

• Open floor for