Angina & Vasodilators

• What is angina pectoris?

  Pain in chest of cardiac origin

  Pain is often referred to left shoulder/upper arm
• What causes angina?

  Inadequate blood & O2 supply to myocardium

  EITHER due to occlusion of coronary arteries (atheroma, progressive) OR due to vasospasm of coronary arteries (rare)
• What is acute coronary syndrome?

  A group of conditions caused by a sudden reduction or blockage of blood flow to the heart, including unstable angina and myocardial infarction.
• What is the difference between stable & unstable angina?

  Stable - usually occurs predictably with physical exertion or emotional stress, lasts for no more than 10 minutes (usually less), and is relieved within minutes of rest, as well as sublingual nitrates

  Unstable - new onset angina or abrupt deterioration in previously stable angina, often occurring at rest. Unstable angina usually requires immediate admission or referral to hospital
• What drugs can be used for stable angina?

  Short acting nitrates (for acute episodes)

  Chronic prevention

  • beta blockers
  • Ca+2 channel blockers
  • Long acting nitrates
  • Nicorandil
  • Ivabradine

  Other vasodilators
• What is the aim of the drugs used for stable angina?

  Sustain balance between O2 delivery & O2 consumpation

  Coronary artery vasodilation -> reduce myocardial effort
• When does coronary blood flow occur?

  Diastole (heart relaxation)
• What is the physiology behind angina?

  Coronary blood flow only occurs is diastole

  If there is increased cardiac work -> less time in diastole -> less perfusion

  Increased sympathetic activity -> increase HR -> less time in diastole & increased contractile force -> more coronary vessel closure (due to pressue) -> decreases cardiac efficiency
• Ischaemic heart develops collateral blood vessels - to redistribute blood to ischaemic areas. (fitness training can also increase collateral circulation)
• How do nitrates work in angina?

  Usually pro-drugs -> when metabolised, release NO

  NO activates NO-sensitive soluble guanylyl cyclase -> increased cGMP -> increase PKG -> vasodilation & other responses (e.g. platelet inhibitions)

  Also has an effect on capacitance veins -> reduced filling pressure -> reduced cardiac effort
• What is coronary 'steal'?

  Redistribution of blood flow away from ischemic myocardium towards non-ischemic myocardium

  Action of dipyridamole

  
• Fill in the blanks

  A) Left coronary artery

  B) Circumflex

  C) Left marginal

  D) Anterior interventricular

  E) Diagonal

  F) Right coronary artery

  G) Right marginal

  H) SAN

  
• How does ACh lead to smooth muscle relaxation?

  ACh released from post-ganglionic parasym nerve endings -> binds to M3 receptors on endothelial cells -> increases Ca+2 -> binds to calmodulin -> activates eNOS (endothelial NO synthase) -> synthesis of NO -> diffuses into smooth muscle cells -> increases cGMP (by NO-sensitive soluble guanylate cyclase) -> cGMP activates PK G -> phosphorylation of proteins (e.g. MLC phosphatase) -> smooth muscle relaxation (via dephosphorylation of myosin)

  cGMP is degraded to GMP by phosphodiesterase (e.g. PDE5)