DRUGS ACTING ON CARDIOVASCULAR SYSTEM

• Myocardial ischemia


  Transient episodes of reduced oxygen supply to the heart muscle
• Angina pectoris


  • Primary symptom of ischemic heart disease
  • Caused by myocardial ischemia
  • Due to imbalance in myocardial oxygen supply-demand relationship
• Causes of myocardial ischemia

  1. Increase in myocardial oxygen demand

  2. Decrease in myocardial oxygen supply

  3. Both
• Blood flow is inversely proportional to the fourth power of the artery's luminal radius
• Progressive decrease in vessel radius that characterizes coronary atherosclerosis can impair coronary blood flow and lead to angina
• Typical angina pectoris


  Anginal symptoms occur with increased myocardial oxygen demand, e.g. with exertion
• Unstable angina


  Anginal symptoms occur due to abrupt reduction in blood flow, e.g. from coronary thrombosis
• Variant or Prinzmetal angina

  Anginal symptoms occur due to coronary vasospasm
• Sensation of angina is similar in most patients - substernal discomfort, often radiating
• Women, the elderly, and diabetics are more likely to have ischemia with atypical symptoms
• Typical angina


  Symptoms relieved by rest or sublingual nitroglycerin
• Drugs used in typical angina

  Reduce myocardial oxygen demand by decreasing heart rate, contractility, and/or ventricular wall stress
• Therapeutic goal in unstable angina

  Increase myocardial blood flow, using antiplatelet agents, heparin, stents, or bypass surgery
• Therapeutic aim in variant/Prinzmetal angina


  Prevent coronary vasospasm
• Antianginal agents may provide prophylactic or symptomatic treatment, and β-blockers can reduce mortality
• Treatment of cardiac risk factors can reduce progression or lead to regression of atherosclerosis
• Organic nitrates


  Prodrugs that are sources of nitric oxide (NO)
• Mechanism of action of nitric oxide

  1. Activates guanylyl cyclase

  2. Increases cyclic GMP

  3. Promotes dephosphorylation of myosin light chain

  4. Reduces cytosolic Ca2+

  5. Leads to smooth muscle relaxation
• Nitric oxide is endogenously synthesized by nitric oxide synthases
• Cardiovascular effects of nitrovasodilators

  • Preferential venodilation over arteriolar dilation
  • Decreases ventricular chamber size and end-diastolic pressures
  • Slight decrease in systemic arterial pressure and pulmonary vascular resistance
  • Headache and facial flushing
• Therapeutic uses of nitrates

  Angina - rapid sublingual administration provides rapid relief
• Nitroglycerin is the most useful sublingual nitrate due to rapid action, efficacy, and low cost
• Patients should seek immediate medical attention if sublingual nitroglycerin does not relieve sustained anginal pain
• Hypertension


  Chronic medical condition of elevated blood pressure in the arteries
• Types of hypertension


  • Primary (essential) hypertension - no obvious underlying cause
  • Secondary hypertension - caused by other medical conditions
• Hypertension is a major risk factor for various cardiovascular and renal complications
• Lifestyle changes can improve blood pressure control, but drug treatment is often necessary
• Uncomplicated hypertension


  Usually occurs without symptoms (silent), can progress for years without being noticed
• Symptoms of uncomplicated hypertension


  Headache, dizziness, shortness of breath, blurred vision with very high blood pressure
• Severe (malignant) hypertension is a medical emergency requiring urgent treatment
• Essential hypertension is associated with high salt intake exceeding 5.8 grams daily
• The presence of symptoms can be a good thing in that they can prompt people to consult a doctor for treatment and make them more compliant in taking their medications
• Often, a person's first contact with a physician may be after significant damage to the body has occurred
• Greater public awareness and frequent blood pressure screening may help to identify patients with undiagnosed high blood pressure before significant complications have developed
• About one out of every 100 (1%) people with hypertension is diagnosed with severe high blood pressure (accelerated or malignant hypertension) at their first visit to the doctor
• In these patients, the diastolic blood pressure exceeds 140 mm Hg!
• Malignant hypertension


  • Affected persons often experience severe headache, nausea, visual symptoms, dizziness, and sometimes kidney failure
  • Malignant hypertension is a medical emergency and requires urgent treatment to prevent a stroke (brain damage)
• Essential hypertension


  Affects approximately 72 million Americans, yet its basic causes or underlying defects are not always known
• Essential hypertension develops only in groups or societies that have a fairly high intake of salt, exceeding 5.8 grams daily
• Salt intake may be a particularly important factor in relation to essential hypertension in several situations, and excess salt may be involved in the hypertension that is associated with advancing age, African American background, obesity, hereditary (genetic) susceptibility, and kidney failure (renal insufficiency)