Coronary Artery Disease Lecture

LEARNING OUTCOMES

  • Understand risk factors and symptoms associated with angina and differentiate types of angina.
  • Describe mechanisms of action of agents used in stable angina treatment.
  • Differentiate between STEMI and NSTEMI.
  • Discuss fibrinolytics' role in MI treatment.
  • Understand long-term management of myocardial infarction including drugs modulating platelet function.
  • Explain mechanisms of lipid-lowering medications and their effects on lipid trafficking.

CORONARY CIRCULATION

  • Functional blood supply to the heart muscle is provided via coronary circulation.
  • Collateral routes ensure blood delivery to cardiac tissue, even when major vessels are occluded.

CORONARY ARTERY DISEASE (CAD)

  • Terms:
    • CAD: refers to coronary artery disease.
    • CHD: refers to symptomatic coronary heart disease.
  • Forms of condition:
    • Unstable angina, myocardial infarction (MI), silent MI, and acute coronary syndrome (ACS).

ATHEROSCLEROSIS

  • Disease affecting large and medium elastic and muscular arteries.
  • Key features:
    • Initial lesion: fatty streaks which may progress to established plaques.
    • Complicated plaques associated with increased inflammation and possible rupture.
  • Can lead to reduced blood supply, heart muscle failure, ischemia.

SIGNS AND SYMPTOMS OF CAD

  • Common signs:
    • Asymptomatic, Chest Pain, Shortness Of Breath, Heart Attack.
  • Angina symptoms:
    • Typically felt as squeezing or pressure in chest.
    • Can also radiate to shoulders, neck, jaw, or back.

TYPES OF ANGINA

  • Stable angina:
    • Most common type; predictable patterns.
    • Occurs during exertion, subsides with rest.
  • Unstable angina:
    • No predictable pattern; not relieved by rest or medication.
    • Risks heart attack.
  • Variant angina (Prinzmetal's):
    • Rare; occurs at rest, usually midnight to early morning.
    • Relieved by medication.

RISK FACTORS

  • Major risk factors include:
    • Hypertension
    • High blood cholesterol
    • Obesity
    • Smoking
    • Diabetes

TREATMENT GOALS IN STABLE ANGINA

  • Balancing myocardial oxygen supply with myocardial oxygen demand:
    • Factors include heart rate, contractility, wall stress.
  • Treatment approaches include beta blockers, calcium channel blockers, hydrazaline, organic nitrates.

MECHANISM OF ACTION

  • Beta-Adrenoceptor Antagonists:
    • Decrease heart rate and contractility, leading to reduced myocardial oxygen demand.
    • Prophylactic use; not for acute angina.
  • Calcium Channel Blockers:
    • Decrease intracellular Ca2+, resulting in reduced cardiac myocyte contraction.
    • Effective in treating various types of angina.
  • Organic Nitrates:
    • Mainstay treatment for angina; examples include GTN.
    • Decrease myocardial oxygen demand by relaxing smooth muscles of blood vessels.

FIBRINOLYTICS

  • Directly break up clots to restore blood flow post-MI.
  • Examples: streptokinase, alteplase, reteplase.
  • Important to consider timing for maximum benefit.

LONG-TERM MANAGEMENT OF MYOCARDIAL INFARCTION

  • Medications:
    • Beta-blockers, ACE inhibitors, nitrates for angina management.
    • Eplerenone for heart failure; antiplatelet drugs to prevent clot formation.
  • Lipid-Focused Treatments:
    • Statins, ezetimibe, PCSK9 inhibitors, and bile acid-binding resins to reduce LDL cholesterol.

PLATELET FUNCTION MODULATORS

  • Aspirin:
    • Inhibits thromboxane A2, reducing platelet aggregation.
  • ADP Antagonists: clopidogrel inhibits P2Y12 receptor; prevents aggregation.
  • PDE Inhibitors: increase intraplatelet cAMP, blocking platelet activation.

THROMBIN AND COAGULATION

  • Actions of thrombin in platelet aggregation; inhibited by heparins and direct thrombin inhibitors.
    • Heparin binds to antithrombin III, accelerating thrombin inhibition.

LIPID-LOWERING MEDICATIONS

  • Statins:
    • Inhibit HMG-CoA reductase, decreasing cholesterol synthesis.
  • Fibrates:
    • Activate PPAR, leading to decreased triglycerides and VLDL.
  • Ezetimibe:
    • Inhibits intestinal cholesterol absorption.
  • Increasing LDL clearance via lifestyle modification and pharmacological interventions is crucial.

SUMMARY

  • Management of coronary artery disease involves understanding the pathology, recognizing the role of various pharmacological agents, and maintaining patient adherence to established treatment strategies.