Anti-Anginal Medications & Angina Types

Anti-anginal Medication Requirements

• Review the Anti-anginal Medication presentation on Brightspace
• Read textbook Chapter 10 (pp 173-177) and be prepared to answer questions 10 and 11
• Review the Ornge Drug Monograph for nitroglycerin
• Review the ALS PCS medical directive for cardiac ischemia (PCP, ACP)
• Review articles on Nitrodilators
• Watch videos on Angina: Stable, Unstable, Microvascular and Prinzmetal
• Watch Nitroglycerin Mechanism of Action for Angina Pectoris
• Watch Anti Anginal Drugs (Part-2) | Beta blockers, Calcium Channel blockers (CCB) | Pharmacology

Learning Objectives

• Review the pathophysiology of angina, unstable angina, and vasospastic angina
• To understand the relationship between oxygen supply and demand in the context of angina
• Learn the factors influencing myocardial workload, oxygen demand, and the development of myocardial ischemia
• Explore how to improve imbalances in the myocardial oxygen supply-demand dynamic
• Understand how anti-anginal medications work to alleviate or prevent angina
• Learn the pharmacology of nitroglycerin
• Apply the MDSO for cardiac ischemia

Key Drugs to Know

• For ALS PCS, know Nitroglycerin
• For emergency care, know Metoprolol, Diltiazem, Verapamil, and Nifedipine
• For home medications, know Isosorbide dinitrate, Amlodipine, Atenolol, and Bisoprolol

Angina Pectoris - Pathophysiology

• Ischemia results when the heart muscle's oxygen demands are not met by the available blood supply which often translates into pain
• The heart needs a substantial oxygen supply
• Normally, the heart uses 5% of cardiac output at rest, with an extraction ratio of 75%, and is influenced by contractility, heart rate, and afterload

Types of Angina

• Chronic stable angina (also called classic or effort angina)
• Unstable angina (also called pre-infarction or crescendo angina)
• Vasospastic angina (also called Prinzmetal, or variant angina)

Myocardial Ischemia Dynamics

• Oxygen demand is determined by factors which include heart rate, myocardial contractility, and intramyocardial wall tension (preload and afterload)
• Oxygen supply is determined by myocardial blood flow
• Myocardial perfusion primarily occurs during diastole, with different ratios for the left (LV 75/25) and right ventricles (RV 50/50)
• Oxygen delivery depends on cardiac output, hemoglobin levels, and arterial oxygen saturation
• Ischemia is defined as an inadequate blood supply to an organ

Heart Health Conditions

• Ischemic heart disease occurs when there is poor blood flow to the heart muscle that results from atherosclerosis or coronary artery disease
• Myocardial infarction (MI) is the necrosis, or death, of cardiac tissue, which can be disabling or fatal

Anti-Anginal Medication Overview

• The two primary goals of angina drug therapy are to prevent myocardial infarction and myocardial ischemia/anginal pain
• Improve blood flow to ischemic heart muscle
• Reduce myocardial oxygen demand
• Reduce the frequency, duration, and intensity of anginal attacks
• Improve the patient's functional capacity while minimizing adverse effects
• Prevent or delay myocardial infarction (MI)

Nitrates - Forms and Action

• Rapid-acting forms are used to treat acute anginal attacks and include sublingual tablets, intravenous infusions, amyl nitrite, and nitroglycerin
• Long-acting forms are used to prevent anginal episodes and include isosorbide dinitrate and isosorbide mononitrate
• Available forms: sublingual, buccal, chewable tablets, oral capsules/tablets, intravenous solutions, transdermal patches/paste.
• Forms marked with * bypass the liver and avoid the first-pass effect

Nitrates and Nitrites Mechanism

• Nitroglycerin activation requires enzymatic action
• Results in the release of free nitrite ion, which is converted to nitric oxide
• Nitric oxide activates guanylyl cyclase, increasing cGMP
• Increased intracellular cGMP inhibits calcium entry, decreasing intracellular calcium and causing smooth muscle relaxation
• Nitric oxide activates K+ channels and causes hyperpolarization and relaxation
• Nitric oxide stimulates a cGMP-dependent protein kinase that activates myosin light chain phosphatase, dephosphorylating myosin light chains and leading to relaxation

Nitrates and Nitrites - Effects and Adverse

• Vasodilation reduces myocardial oxygen demand by decreasing preload and afterload
• Nitrates dilate both large and small coronary vessels, with venous and arterial dilation being dose-dependent
• Alleviate coronary artery spasms
• Adverse effects of nitrates include headaches, which usually diminish with use, tachycardia, and postural hypotension
• Tolerance can develop with continuous nitrate use
• Tolerance can be avoided by incorporating a regular nitrate-free interval that allows enzyme pathways to replenish
• With transdermal forms, this is achieved by removing the patch at bedtime for 8 hours and applying a new patch in the morning

Nitroglycerin - Action

• Forms nitric oxide, leading to smooth muscle relaxation and vasodilation
• Reduces cardiac oxygen demand by decreasing preload
• Dilates coronary arteries and improves collateral flow to ischemic regions

Nitroglycerin - Indications

• Treatment of angina pectoris
• CHF associated with acute MI
• Control of severe hypertension as in hypertensive emergency
• As a tocolytic agent for the treatment of uterine tachysystole during pregnancy or labor

Nitroglycerin - Contraindications and Adverse

• Contraindications include hypersensitivity or allergy
• Contraindications include the use of phosphodiesterase-5 Inhibitors (within 48 hrs)
• Use with caution in patients with right ventricular MI, hypotension, bradycardia, or tachycardia
• Adverse effects: CV: excessive hypotension, reflex tachycardia, CNS: headache, dizziness, weakness, restlessness, GI: nausea, vomiting, abdominal pain

Beta Blockers - Properties

• 1st generation: Non-selective, without vasodilation e.g. Propranolol, Timolol, Pindolol, Nadolol, Sotalol
• 2nd generation: B1-selective without vasodilation e.g. Atenolol, Bisoprolol, Metoprolol
• 2nd generation: B1 selective with vasodilation e.g. Nebivolol, Acebutolol
• 3rd generation: Non-selective with vasodilation e.g. Carvedilol, Bucindolol

Beta Blockers - Action

• Block β1-receptors on the heart and prevent the binding of epinephrine and norepinephrine
• Prevent activation of adenylyl cyclase, which form cAMP, preventing phosphorylation of calcium channels, and reducing calcium release by the sarcoplasmic reticulum
• Results in decreased chronotropy (heart rate) and inotropy (contractility), reducing myocardial workload
• Blocks the harmful effects of catecholamines and improve survival after acute MI when high levels of catecholamines irritate causing an imbalance in supply and demand

Beta Blockers in Angina and MI

• Reduce heart rate, blood pressure, and contractility, decreasing myocardial oxygen requirements at rest and during exercise
• Lower heart rate increases diastolic perfusion time, which may improve coronary perfusion
• Can be valuable in treating silent or ambulatory ischemia
• Reduce mortality in patients with recent MI

Beta Blockers - Contra and Adverse

• Contraindications: asthma, bronchospastic conditions, severe bradycardia, atrioventricular blockade, bradycardia-tachycardia syndrome, unstable left ventricular failure
• Adverse effects: increasing end-diastolic volume and ejection time that tend to increase myocardial oxygen requirements, fatigue, impaired exercise tolerance, insomnia, unpleasant dreams, worsening of claudication, and erectile dysfunction

Calcium Channel Blockers (CCBs)

• Dihydropyridine subclass: includes amlodipine, felodipine, isradipine, nicardipine & nifedipine
• Phenylalkylamine subclass: includes verapamil hydrochloride
• Benzothiazepine subclass: includes diltiazem

Calcium Channel Blockers - Action

• CCBs bind to L-type calcium channels on vascular smooth muscle and cardiac myocytes, reducing calcium influx
• The affect causes a reduction in the release of calcium from the sarcoplasmic reticulum, leading to smooth muscle relaxation
• Results in vascular smooth muscle relaxation (vasodilation), decreased myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decreased conduction velocity within the heart (negative dromotropy)

Calcium Channel Blockers - Effects in Angina

• CCBs effects derived from vasodilatory and cardiodepressant actions that reduce arterial pressure and ventricular afterload, decreasing oxygen demand
• Cardioselective CCBs like verapamil and diltiazem reduce heart rate and contractility, decreasing myocardial oxygen demand
• CCBs dilate coronary arteries and prevent/reverse coronary vasospasm while increasing oxygen supply to the myocardium

Calcium Channel Blockers - Adverse

• Contraindications: Preexistent bradycardia, conduction defects, or heart failure caused by systolic dysfunction or the use of beta blockers
• Adverse effects: Flushing, headache, excessive hypotension, edema, reflex tachycardia, bradycardia, conduction blocks.
• CCB's used in angina: Diltiazem, verapamil, amlodipine, nicardipine, nifedipine

Case 1

• Fleurette is 68 years old and experiencing chest discomfort, nausea, and shortness of breath
• She has a history of angina, but today’s discomfort is more severe than previously
• Information needed to initiate NTG protocol?
• What complications should be considered or prepared for?