2b

COURSE OUTLINE

• I. ANGINA PECTORIS
  • A. Pathophysiology
• II. DRUGS FOR ANGINA PECTORIS
  • A. Traditional Drugs
  • B. Newer Antianginal Drugs
  • C. Clinical Pharmacology used to treat Angina

I. ANGINA PECTORIS

• Angina pectoris denotes chest pain caused by the accumulation of metabolites resulting from myocardial ischemia.
• The most common cause of angina is atheromatous obstruction of the large coronary vessels (coronary artery disease, CAD).
• Characteristics of angina:
  • Strangling or pressure-like pain
  • Usually located substernally
  • May radiate to the neck, shoulder, arm, or epigastrium caused by cardiac ischemia.
• Drugs: Two main strategies for treatment of angina include:
  • Reduction of oxygen demand
  • Increase of oxygen delivery to the myocardium.

Figure 1: Pharmacological Modification of Major Determinants of Myocardial O2 Supply

• When myocardial O2 requirements exceed O2 supply, an ischemic episode results.
• This figure illustrates the primary hemodynamic sites of pharmacological agents that can reduce O2 demand (left side) or enhance O2 supply (right side).
• Some classes of agents have multiple effects.
• Mechanical Interventions:
  • Stents, angioplasty, and coronary bypass surgery are mechanical methods that increase O2 supply.
  • Both pharmacotherapy and mechanotherapy attempt to restore a dynamic balance between O2 demand and O2 supply.
• Preload: a function of blood volume and venous tone controlled by sympathetic activity.
• Afterload: determined by arterial BP and large artery thickness, it is one of the systolic determinants of oxygen requirement.

Drug Groups Used in Angina

• Traditional classes of drugs include:
  • Beta-blockers
  • Calcium channel blockers
  • Nitrates

A. PATHOPHYSIOLOGY

A.1. TYPES OF ANGINA

ATHEROSCLEROTIC ANGINA

• Also known as:
  • Angina of effort
  • Classic angina
  • Stable angina
• Mechanism: Atheromatous plaques partially occlude coronary arteries.
• Diagnosis is generally based on patient history and stress testing.
• Key features:
  • Complete relief at rest
  • Accounts for 90% of angina cases.

VASOSPASTIC ANGINA

• Other names include:
  • Rest angina
  • Variant angina
  • Prinzmetal’s angina
• Accounts for less than 10% of angina cases.
• Features a reversible spasm of a vessel wall (normal or atherosclerotic) that may occur at any time, even during sleep.

UNSTABLE ANGINA

• Also known as:
  • Crescendo angina
  • Acute coronary syndrome
• Features increased frequency, duration, and severity of attacks.
• Mechanism: Combination of atherosclerotic plaques, platelet aggregation at fractured plaques, and vasospasm.
• Commonly results from formation of labile, partially occlusive thrombi at the site of a fissured or ulcerated plaque.
• Inflammation may be a risk factor. Patients on tumor necrosis factor inhibitors show a lower risk of myocardial infarction.
• It is a precursor of myocardial infarction (MI) and qualifies as a medical emergency.

Figure 4: Stable vs Unstable Angina

• Diagram of unstable angina highlighting the rupture of atherosclerotic plaque, causing platelet aggregation, leading to partial occlusion of the blood vessel. This can intensify to total occlusion resulting in myocardial infarction.

II. DRUGS FOR ANGINA PECTORIS

TYPE DESCRIPTION

• Traditional Drugs
  • Nitrates
  • Calcium channel blockers
  • Beta-blockers
• Newer Drugs:
  • Trimetazidine: Increases efficiency of O2 utilization; acts as metabolic modulators.
  • Ranolazine: Inhibits late sodium current.
  • Ivabradine: Reduces heart rate by inhibition of SA pacemaker current (If).

Table 2: Drugs for Angina Pectoris

Figure 6: Mechanism of Anti-Anginal Drugs

• The drugs exploit two strategies to manage angina:
  • Decrease oxygen demand
  • Increase oxygen delivery to myocardium
• These agents:
  • Increase regional flow and distribution
  • Decrease heart rate thus lowering oxygen demand
  • Decrease peripheral vascular resistance via calcium channel blockers
  • Nitrates function as venous dilators, decreasing preload, and increase coronary blood flow.