Nursing Pharmacology Chapter 9:  Antianginal Drugs

• Coronary blood flow regulation:

  • Coronary blood flow is controlled by the myocardial oxygen demand and modulated by varying coronary vascular resistance considerably.

  • The myocardium extracts a fixed and high percentage of oxygen.

    • In the absence of atherosclerotic disease, intramyocardial resistance arterioles can significantly dilate.

  • By regulation of smooth muscle tone, intramyocardial arterioles (resistance vessels) a balance is maintained between coronary blood flow and myocardial oxygen requirement.

  • In healthy individuals, the large epicardial vessels are conductance vessels.

Selwyn, A.P. and Braunwald, E Ischemic Heart Disease in Harrison's Principles of Internal Medicine (Isselbacher et al., eds) McGraw-Hill, Inc., New York, 1994, p 1077.

• Factors Influencing Myocardial Oxygen Supply and Demand

  This figure illustrates the factors that affect myocardial oxygen demand and supply. Drugs that may prevent or terminate angina may: Either increase oxygen supply (coronary vasodilators) and/or Reduce oxygen demand (negative chrontropic drugs, vasodilators, and negative inotropic agents.) Raehl, C.L., and Nolan, P.E. Ischemic Heart Disease: Anginal Syndromes in Applied Therapeutics: The Clinical Use of Drugs (Young, L.Y., and Koda-Kimble, M.A., eds), Applied Therapeutics, Inc., Vancouver, 1995, p 13-3.

• Control of coronary blood flow involves:

• Local metabolism

• Nervous system regulation.

• More important of these two mechanism is local myocardial metabolism, i.e. local arterial vasodilation is regulated by myocardial requirements.

  • Normally, increases in coronary blood flow, even in a denervated heart, occurs in response to increased myocardial contractility and rate.

  • Production of local vasodilator products may be responsible.

  • Candidates for these vasodilatory substances include:

    1. Adenosine

    2. Prostaglandins

    3. Potassium ions

    4. Bradykinin

    5. Hydrogen ions

    6. Carbon dioxide

    7. Nitric oxide

• Autonomic nervous system activity can affect coronary vasculature tone.

  • On the parasympathetic (vagal) side: there are so few fibers terminating on the coronary vasculature that the vagal dilating effects are minimal.

  • Coronary vascular bed has both alpha and beta-adrenoceptors.

    • α-adrenergic receptor activation produces constriction, mainly in epicardial capacitance vessels when these receptors are mostly found.

    • Coronary vessel vasodilation is mediated by β-adrenoceptors which are mainly localized in intramuscular arteries.

  • Sympathetic activation probably produces more constriction than dilation and in individuals with accentuated responses to α-receptor activation may be susceptible to vasospastic myocardial ischemia

Guyton, A.C. and Hall, J.E. in Textbook of Medical Physiology, W.B. Saunders & Co., Philadephia, 1984, p 258-259.