Medical 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]

• The figure above illustrates the factors that affect myocardial oxygen demand and supply.

  • Drugs that may prevent or terminate angina may:

    1. Either increase oxygen supply (coronary vasodilators) and/or

    2. 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

  • 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-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.

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