Pharmacology Lecture: Stable Ischemic Heart Disease

Stable Ischemic Heart Disease (SIHD)

• Professor Hany A. Omar's lecture objectives:
  • Understand rationale for drug therapy in ischemic heart diseases
  • Know classes of drugs used to treat myocardial infarction
  • Mode of action of nitrates
  • Pharmacokinetics of nitrates and their formulations and delivery methods
  • Clinical uses and common side effects of nitrates
  • Concept of nitrate tolerance
  • Different types of fibrinolytics and their mechanisms of action

Angina Pectoris

• Ischemic myocardial pain resulting from imbalance between oxygen supply and demand
• Main symptoms:
  • Severe chest pain due to ischemia of the heart muscle
  • Pain extending to shoulders, arms, neck, jaw, or back
  • Feeling like pressure or squeezing in the chest
• Types of angina:
  • Stable (effort) angina: occurs with physical effort, relieved by rest, and has a regular pattern
  • Unstable angina: occurs with increased frequency, precipitated by less effort, and may not be relieved by rest or nitroglycerin
  • Variant (Prinzmetal's) angina: rare, occurs due to coronary vasospasm, usually at rest, and relieved by medicine

Differences between Angina Pectoris and Myocardial Infarction

• Angina pectoris: reversible process, no permanent damage to the muscle
• Myocardial infarction: ischemic necrosis due to total occlusion of coronary artery, irreversible changes in muscle

Treatment of Angina Pectoris

• Treatment lines include:
  • Vasodilators (increase oxygen supply)
  • Agents that decrease oxygen demand (decrease myocardial work)
• Examples:
  • Organic nitrates (e.g., Isosorbide dinitrate, Glyceryltrinitrate/Nitroglycerin)
  • Mechanism of action: release nitric oxide, which vasodilates blood vessels, increases oxygen supply, and decreases oxygen demand

Nitrates & Nitrites

• Cardiovascular effects:
  • Vasodilatation in veins, arteries, and coronaries
  • Decrease preload, ventricular filling pressure, cardiac work, and oxygen demand
• Antiplatelet aggregation effect: NO stimulates increase in cGMP in platelets, decreasing platelet aggregation
• Pharmacokinetics:
  • Short-acting: sublingual (Nitroglycerin, Isosorbide dinitrate), inhalation (Amyl nitrite)
  • Long-acting: oral sustained-release nitrite (Nitroglycerin), transdermal patches (Nitroglycerin), oral (Isosorbide dinitrate)
• Contraindications:
  • Hypotension (systolic < 180 or diastolic < 110)
  • Recent surgery
  • Warfarin therapy
  • Active peptic ulcer
  • Diabetic retinopathy and history of hypertension
  • Ischemic stroke (?)

Fibrinolytic Agents

• Complications:
  • Bleeding (most common)
  • Intra-cranial hemorrhage (most serious, 0.5-0.7%)
  • Liberation of platelets and thrombin from the clot, potentially causing another clot in other sites
• Interactions:
  • Aspirin and heparin increase activity and risk of bleeding of fibrinolytics
• Examples:
  • Streptokinase: protein produced by streptococci, forms a complex with plasminogen, converting it to plasmin
  • Complications and adverse effects:
    • Allergic reactions in patients with prior exposure to streptococci

Stable Ischemic Heart Disease (SIHD)

• Professor Hany A. Omar's lecture objectives:
  • Understand rationale for drug therapy in ischemic heart diseases
  • Know classes of drugs used to treat myocardial infarction
  • Mode of action of nitrates
  • Pharmacokinetics of nitrates and their formulations and delivery methods
  • Clinical uses and common side effects of nitrates
  • Concept of nitrate tolerance
  • Different types of fibrinolytics and their mechanisms of action

Angina Pectoris

• Ischemic myocardial pain resulting from imbalance between oxygen supply and demand
• Main symptoms:
  • Severe chest pain due to ischemia of the heart muscle
  • Pain extending to shoulders, arms, neck, jaw, or back
  • Feeling like pressure or squeezing in the chest
• Types of angina:
  • Stable (effort) angina: occurs with physical effort, relieved by rest, and has a regular pattern
  • Unstable angina: occurs with increased frequency, precipitated by less effort, and may not be relieved by rest or nitroglycerin
  • Variant (Prinzmetal's) angina: rare, occurs due to coronary vasospasm, usually at rest, and relieved by medicine

Differences between Angina Pectoris and Myocardial Infarction

• Angina pectoris: reversible process, no permanent damage to the muscle
• Myocardial infarction: ischemic necrosis due to total occlusion of coronary artery, irreversible changes in muscle

Treatment of Angina Pectoris

• Treatment lines include:
  • Vasodilators (increase oxygen supply)
  • Agents that decrease oxygen demand (decrease myocardial work)
• Examples:
  • Organic nitrates (e.g., Isosorbide dinitrate, Glyceryltrinitrate/Nitroglycerin)
  • Mechanism of action: release nitric oxide, which vasodilates blood vessels, increases oxygen supply, and decreases oxygen demand

Nitrates & Nitrites

• Cardiovascular effects:
  • Vasodilatation in veins, arteries, and coronaries
  • Decrease preload, ventricular filling pressure, cardiac work, and oxygen demand
• Antiplatelet aggregation effect: NO stimulates increase in cGMP in platelets, decreasing platelet aggregation
• Pharmacokinetics:
  • Short-acting: sublingual (Nitroglycerin, Isosorbide dinitrate), inhalation (Amyl nitrite)
  • Long-acting: oral sustained-release nitrite (Nitroglycerin), transdermal patches (Nitroglycerin), oral (Isosorbide dinitrate)
• Contraindications:
  • Hypotension (systolic < 180 or diastolic < 110)
  • Recent surgery
  • Warfarin therapy
  • Active peptic ulcer
  • Diabetic retinopathy and history of hypertension
  • Ischemic stroke (?)

Fibrinolytic Agents

• Complications:
  • Bleeding (most common)
  • Intra-cranial hemorrhage (most serious, 0.5-0.7%)
  • Liberation of platelets and thrombin from the clot, potentially causing another clot in other sites
• Interactions:
  • Aspirin and heparin increase activity and risk of bleeding of fibrinolytics
• Examples:
  • Streptokinase: protein produced by streptococci, forms a complex with plasminogen, converting it to plasmin
  • Complications and adverse effects:
    • Allergic reactions in patients with prior exposure to streptococci

Stable Ischemic Heart Disease (SIHD)

• Professor Hany A. Omar's lecture objectives:
  • Understand rationale for drug therapy in ischemic heart diseases
  • Know classes of drugs used to treat myocardial infarction
  • Mode of action of nitrates
  • Pharmacokinetics of nitrates and their formulations and delivery methods
  • Clinical uses and common side effects of nitrates
  • Concept of nitrate tolerance
  • Different types of fibrinolytics and their mechanisms of action

Angina Pectoris

• Ischemic myocardial pain resulting from imbalance between oxygen supply and demand
• Main symptoms:
  • Severe chest pain due to ischemia of the heart muscle
  • Pain extending to shoulders, arms, neck, jaw, or back
  • Feeling like pressure or squeezing in the chest
• Types of angina:
  • Stable (effort) angina: occurs with physical effort, relieved by rest, and has a regular pattern
  • Unstable angina: occurs with increased frequency, precipitated by less effort, and may not be relieved by rest or nitroglycerin
  • Variant (Prinzmetal's) angina: rare, occurs due to coronary vasospasm, usually at rest, and relieved by medicine

Differences between Angina Pectoris and Myocardial Infarction

• Angina pectoris: reversible process, no permanent damage to the muscle
• Myocardial infarction: ischemic necrosis due to total occlusion of coronary artery, irreversible changes in muscle

Treatment of Angina Pectoris

• Treatment lines include:
  • Vasodilators (increase oxygen supply)
  • Agents that decrease oxygen demand (decrease myocardial work)
• Examples:
  • Organic nitrates (e.g., Isosorbide dinitrate, Glyceryltrinitrate/Nitroglycerin)
  • Mechanism of action: release nitric oxide, which vasodilates blood vessels, increases oxygen supply, and decreases oxygen demand

Nitrates & Nitrites

• Cardiovascular effects:
  • Vasodilatation in veins, arteries, and coronaries
  • Decrease preload, ventricular filling pressure, cardiac work, and oxygen demand
• Antiplatelet aggregation effect: NO stimulates increase in cGMP in platelets, decreasing platelet aggregation
• Pharmacokinetics:
  • Short-acting: sublingual (Nitroglycerin, Isosorbide dinitrate), inhalation (Amyl nitrite)
  • Long-acting: oral sustained-release nitrite (Nitroglycerin), transdermal patches (Nitroglycerin), oral (Isosorbide dinitrate)
• Contraindications:
  • Hypotension (systolic < 180 or diastolic < 110)
  • Recent surgery
  • Warfarin therapy
  • Active peptic ulcer
  • Diabetic retinopathy and history of hypertension
  • Ischemic stroke (?)

Fibrinolytic Agents

• Complications:
  • Bleeding (most common)
  • Intra-cranial hemorrhage (most serious, 0.5-0.7%)
  • Liberation of platelets and thrombin from the clot, potentially causing another clot in other sites
• Interactions:
  • Aspirin and heparin increase activity and risk of bleeding of fibrinolytics
• Examples:
  • Streptokinase: protein produced by streptococci, forms a complex with plasminogen, converting it to plasmin
  • Complications and adverse effects:
    • Allergic reactions in patients with prior exposure to streptococci