Nitrates and Angina Management: Detailed Notes

Anti-Anginal Drugs

  • Three main groups of drugs to treat angina:
    • Nitrates
    • Calcium channel blockers
    • Beta-adrenergic blockers

The Cardiovascular System

  • Vasculature is a system of interconnected tubes (arteries, veins, capillaries) that moves blood throughout the body.
  • Functions:
    • Circulates blood to provide oxygen and nutrients
    • Assists in dispose of metabolic wastes

Functions of the Heart

  • Generates blood pressure
  • Routes blood
  • Ensures one-way blood flow
  • Regulates blood supply

Understanding Angina

  • Definition: Angina is a type of chest pain or discomfort due to insufficient oxygen supply to the heart.
  • It occurs when there is an imbalance between the oxygen demand of the heart and the oxygen supplied by coronary vessels.
Types of Angina
  1. Classic Angina:
    • Caused by vessel occlusion (atherosclerosis).
    • Chest pain not experienced at rest because myocardial oxygen supply remains balanced.
  2. Vasospastic/Prinzmetal's Angina:
    • Occurs due to artery spasm leading to constricted blood flow.
    • Spasms can be unpredictable and unrelated to activity.
  3. Silent Angina:
    • Occurs without experiencing chest pain.
  4. Unstable Angina:
    • Occurs when a plaque in the coronary artery ruptures, forming a thrombus and possibly blocking the artery.

Risk Factors for Angina

  • Atherosclerosis
  • Cigarette smoking
  • Diabetes
  • Hypercholesterolemia
  • Hypertension
  • Heredity
  • Age
  • Inactive lifestyle
  • Obesity

Drug Therapy for Angina

  • Aimed at restoring the balance between myocardial oxygen supply and demand.

Nitrates in Angina Treatment

  • Mechanism: Nitrates exert vasodilatory effects.
  • Main Effect: Dilation of veins decreases blood returning to the heart.
  • Pathway:
    • Nitric oxide stimulates guanylyl cyclase → increases cGMP → leads to vasodilation of veins and arteries.
  • In vasospastic angina, nitrates can relax spasms, allowing more oxygen to reach the myocardium.
Classification of Nitrates
  • Rapidly Acting Nitrates:
    • Nitroglycerin: Available as sublingual tablet/spray, oral sustained-release, and transdermal.
  • Long-Acting Nitrates:
    • Isosorbide dinitrate & Isosorbide mononitrate
Key Nitrate Preparations and Their Effects
PreparationOnset of ActionDuration of Action
Nitroglycerin (sublingual)1-3 min30 min
Isosorbide dinitrate (sublingual)5 min30-60 min
Isosorbide mononitrate (oral)30 min12-24 h

Heart Failure

  • Definition: Progressive inability of the heart to supply adequate blood flow.
  • Symptoms include coughing, tiredness, shortness of breath, swelling in abdomen, ankles, and legs due to fluid accumulation (edema).
Mechanisms of Action of Drugs for Heart Failure
  • Adrenergic blockers: Slow heart rate (B₁) and decrease blood pressure (alpha).
  • Cardiac glycosides: Increase force of myocardial contraction.
  • Vasodilators: Dilate vessels, reducing preload.
  • Diuretics: Reduce fluid volume, decreasing blood pressure.

Treatment of Heart Failure with Nitrates

  • Example: Isosorbide dinitrate relaxes blood vessels and lowers blood pressure but is not very effective as monotherapy.

Side Effects of Nitrates

  • Headache
  • Dizziness
  • Nausea
  • Flushing
  • Low blood pressure

Contraindications for Nitrates

  • Patients with hypotension
  • Closed-angle glaucoma
  • Increased intracranial pressure
  • Hyperthyroidism

Drug Interactions

  • Nitrates may interact with PDE5 inhibitors (e.g., Sildenafil, Vardenafil, Tadalafil) as they can enhance vasodilation effects.