Antianginal Agents

Coronary Ischemia: Supply and Demand Economics

Coronary Ischemia: Supply and Demand Economics

The Grip of Angina

Supply-Demand Mismatch

Myocardial Oxygen Demand Heart Rate Wall Stress Contractility Adapted from Runge et al, Netter’s Cardiology

Determinants of Myocardial Oxygen Supply

Determinants of Myocardial Oxygen Supply

Coronary Flow Reserve Adapted from Maseri A, Ischemic Heart Disease, Churchill Livingstone, 1995

Angina Pectoris (Chest Pain) When the supply of oxygen and nutrients in the blood is insufficient to meet the demands of the heart, the heart muscle aches. The heart demands a large supply of oxygen to meet the demands placed on it.

Types of Angina Chronic stable angina (also called classic or effort angina) Unstable angina (also called preinfarction or crescendo angina) Vasospastic angina (also called Prinzmetal’s or variant angina)

Angina Drug Therapy

Antianginal Agents Nitrates Beta blockers Calcium channel blockers

Antianginal Agents: Therapeutic Objectives Increase blood flow to ischemic heart muscle and/or Decrease myocardial oxygen demand

Antianginal Agents: Therapeutic Objectives Minimize the frequency of attacks and decrease the duration and intensity of anginal pain Improve the patient’s functional capacity with as few side effects as possible Prevent or delay the worst possible outcome, MI

Nitric Oxide Opie LH: Heart Physiology Lippincot Williams & Wilkins, 2004

Antianginal Agents: Nitrates Available forms: Sublingual Ointments Buccal Transdermal patches Chewable tablets Inhalable sprays Capsules Intravenous solutions

Antianginal Agents: Nitrates Cause vasodilation due to relaxation of smooth muscles Potent dilating effect on coronary arteries Used for prophylaxis and treatment of angina

Antianginal Agents: Nitrates Nitroglycerin Prototypical nitrate Large first-pass effect with PO forms Used for symptomatic treatment of ischemic heart conditions (angina) IV form used for BP control in perioperative hypertension, treatment of CHF, ischemic pain, and pulmonary edema associated with acute MI

Antianginal Agents: Nitrates isosorbide dinitrate (Isordil, Sorbitrate, Dilatrate SR) isosorbide mononitrate (Imdur, Monoket, ISMO) Used for: Acute relief of angina Prophylaxis in situations that may provoke angina Long-term prophylaxis of angina

Antianginal Agents: Nitrates Side Effects Headache Usually diminish in intensity and frequency with continued use Tachycardia, postural hypotension Tolerance may develop

Nitrate Tolerance Occurs with chronic administration of long acting nitrates. Efficacy of drug diminishes with chronic exposure (tachyphylaxis). Tolerance readily reverses with nitrate free interval.

Antianginal Agents: Beta Blockers atenolol (Tenormin) metoprolol (Lopressor) propranolol (Inderal) nadolol (Corgard)

Adrenergic Receptors Beta1 Beta2 Alpha SA node, AV node, His-Purkinje system Myocardium Juxtaglomerular apparatus Adipocytes Beta2 Peripheral and coronary vasculature Bronchi Peripheral Muscle Uterine Muscle Alpha Peripheral circulation Beta-1 Beta-2 Alpha Adapted from Runge et al, Netter’s Cardiology

Antianginal Agents: Beta Blockers Mechanism of Action Decrease the HR, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heart Decrease myocardial contractility, helping to conserve energy or decrease demand

Antianginal Agents: Beta Blockers Therapeutic Uses Antianginal Antihypertensive Cardioprotective effects, especially after MI

Antianginal Agents: Beta Blockers Side Effects Body System Effects Cardiovascular bradycardia, hypotension second- or third-degree heart block heart failure Metabolic Altered glucose and lipid metabolism

Antianginal Agents: Beta Blockers Side Effects Body System Effects CNS dizziness, fatigue, mental depression, lethargy, drowsiness, unusual dreams Other impotence wheezing, dyspnea

Antianginal Agents: Calcium Channel Blockers verapamil (Calan) diltiazem (Cardizem) nifedipine (Procardia)

Role of Calcium Channels in Myocardial Contraction Opie LH, Heart Physiology, Williams Lippincott and Williams 2004

Role of Calcium Channel in Vascular Smooth Muscle Function Opie LH, Heart Physiology, Williams Lippincott and Williams 2004

Antianginal Agents: Calcium Channel Blockers Mechanism of Action Cause peripheral arterial vasodilation Reduce myocardial contractility (negative inotropic action) Result: decreased myocardial oxygen demand

Antianginal Agents: Calcium Channel Blockers Therapeutic Uses First-line agents for treatment of angina, hypertension, and supraventricular tachycardia Short-term management of atrial fibrillation and flutter Several other uses

Antianginal Agents: Calcium Channel Blockers Side Effects Very acceptable side effect and safety profile May cause hypotension, palpitations, tachycardia or bradycardia, constipation, nausea, dyspnea

Treatment of Ischemic Heart Disease

Antianginal Agents: Nursing Implications Before administering, perform a complete health history to determine presence of conditions that may be contraindications for use or call for cautious use. Obtain baseline VS, including respiratory patterns and rate. Assess for drug interactions.

Antianginal Agents: Nursing Implications Patients should not take any medications, including OTC medications, without checking with the physician. Patients should report blurred vision, persistent headache, dry mouth, dizziness, edema, fainting episodes, weight gain of 2 pounds in 1 day or 5 or more pounds in 1 week, pulse rates under 60, and any dyspnea.

Antianginal Agents: Nursing Implications Alcohol consumption and hot baths or spending time in jacuzzis, hot tubs, or saunas will result in vasodilation, hypotension, and the possibility of fainting. Teach patients to change positions slowly to avoid postural BP changes. Encourage patients to keep a record of their anginal attacks, including precipitating factors, number of pills taken, and therapeutic effects.

Antianginal Agents: Nitroglycerin Nursing Implications Instruct patients in proper technique and guidelines for taking sublingual NTG for anginal pain. Instruct patients never to chew or swallow the SL form. Instruct patients that a burning sensation felt with SL forms indicates that the drug is still potent.

Antianginal Agents: Nitroglycerin Nursing Implications Patients are taught to take up to three tablets every 5 minutes. If no relief from chest pain is obtained after three tablets, they should seek medical assistance. Absorption nitroglycerin ointments best over a nonfatty and nonhairy portion of skin. The upper torso is the preferred site of application. The nurse should wear gloves when applying to prevent transdermal absorption by the applier. The ointment is measured as one straight line on the nitroglycerin patch and is gently spread over paper and applied, but not rubbed, into the skin.

Antianginal Agents: Nitroglycerin Nursing Implications Instruct patients to keep a fresh supply of NTG on hand; potency is lost in about 3 months after the bottle has been opened. Medications should be stored in an airtight, dark glass bottle with a metal cap and no cotton filler to preserve potency.

Antianginal Agents: Nitroglycerin Nursing Implications Instruct patients in the proper application of nitrate topical ointments and transdermal forms, including site rotation and removal of old medication. To reduce tolerance, the patient may be instructed to remove topical forms at bedtime, and apply new doses in the morning, allowing for a nitrate-free period.

Antianginal Agents: Nitroglycerin Nursing Implications Instruct patients to take prn nitrates at the first hint of anginal pain. If experiencing chest pain, the patient taking SL NTG should be lying down to prevent or decrease dizziness and fainting that may occur due to hypotension. Monitor VS frequently during acute exacerbations of angina and during IV administration.

Antianginal Agents: Nitroglycerin Nursing Implications IV forms of NTG must be contained in glass IV bottles and must be given with infusion pumps. Discard parenteral solution that is blue, green, or dark red. Follow specific manufacturer’s instructions for IV administration. Use special IV tubing provided or non-PVC tubing.

Antianginal Agents: Calcium Channel Blockers Nursing Implications Blood levels should be monitored to ensure they are therapeutic. Oral CCBs should be taken before meals and as ordered. Patients should be encouraged to limit caffeine intake.

Antianginal Agents: Beta Blockers Nursing Implications Patients taking beta blockers should monitor pulse rate daily and report any rate lower than 60 beats per minute. Dizziness or fainting should also be reported. Constipation is a common problem. Instruct patients to take in adequate fluids and eat high-fiber foods.

Antianginal Agents: Beta Blockers Nursing Implications These medications should never be abruptly discontinued due to risk of rebound hypertensive crisis. Inform patients that these medications are for long-term prevention of angina, not for immediate relief.

Antianginal Agents: Nursing Implications Monitor for adverse reactions Allergic reactions, headache, light-headedness, hypotension, dizziness Monitor for therapeutic effects Relief of angina, decreased BP, or both

Antidysrhythmic Agents

Antidysrhythmics Dysrhythmia Antidysrhythmics Any deviation from the normal rhythm of the heart Antidysrhythmics Drugs used for the treatment and prevention of disturbances in cardiac rhythm

Cardiac Cell Inside the cardiac cell, there exists a net negative charge relative to the outside of the cell.

Resting Membrane Potential: RMP This difference in the electronegative charge. Results from an uneven distribution of ions (sodium, potassium, calcium) across the cell membrane. An energy-requiring pump is needed to maintain this uneven distribution of ions. Sodium-potassium ATPase pump

Heart and Conduction System

Resting Membrane Potential of a Cardiac Cell

Abnormal Heart Rhythms Arrhythmia BPM tachycardia 150-250 bradycardia <60 atrial flutter 200-350 atrial fibrilation >350 prem. atrial cont. variable prem. vent. cont. vent. fibrilation

Premature Ventricular Contraction

Action Potential A change in the distribution of ions causes cardiac cells to become excited. The movement of ions across the cardiac cell’s membrane results in the propagation of an electrical impulse. This electrical impulse leads to contraction of the myocardial muscle.

Action Potential Four Phases The SA node and the Purkinje cells each have separate action potentials.

Action Potentials: Phases (SA Node)

Action Potentials: Purkinje Fiber

Action Potentials: Intervals

Abnormal Heart Rhythms Caused by: ischemia, infarction, alteration of body chemicals Symptoms: palpitations, syncope, lightheadedness, visual disturbances, pallor, cyanosis, weakness, sweating, chest pain, hypotension

Pharmaceutical Treatment Aimed at preventing life-threatening conditions by restoring normal rhythm Acts on the myocardium where the impulses are conducted Some drugs influence heart rate, others influence movement of ions (Na and Ca)

Vaughan Williams Classification System commonly used to classify antidysrhythmic drugs

Vaughan Williams Classification Class Ia Class Ib Class Ic Class II Class III Class IV Other

Vaughan Williams Classification Membrane-stabilizing agents Fast sodium channel blockers Divided into Ia, Ib, and Ic agents, according to effects

Vaughan Williams Classification moricizine General Class I agent Has characteristics of all three subclasses Used for symptomatic ventricular and life-threatening dysrhythmias

Vaughan Williams Classification Class Ia quinidine, procainamide, disopyramide Block sodium channels Delay repolarization Increase the APD Used for atrial fibrillation, premature atrial contractions, premature ventricular contractions, ventricular tachycardia, Wolff-Parkinson-White syndrome

Vaughan Williams Classification Class Ib tocainide, mexiletine, phenytoin, lidocaine Block sodium channels Accelerate repolarization Decrease the APD Used for ventricular dysrhythmias only (premature ventricular contractions, ventricular tachycardia, ventricular fibrillation)

Vaughan Williams Classification Class Ic encainide, flecainide, propafenone Block sodium channels (more pronounced effect) Little effect on APD or repolarization Used for severe ventricular dysrhythmias May be used in atrial fibrillation/flutter

Vaughan Williams Classification Class II Beta blockers: atenolol, esmolol, petaprolol, propranolol Reduce or block sympathetic nervous system stimulation, thus reducing transmission of impulses in the heart’s conduction system Depress phase 4 depolarization General myocardial depressants for both supraventricular and ventricular dysrhythmias

Vaughan Williams Classification Class III amiodarone, bretylium, sotalol, ibutilide Increase APD Prolong repolarization in phase 3 Used for dysrhythmias that are difficult to treat Life-threatening ventricular tachycardia or fibrillation, atrial fibrillation or flutter—resistant to other drugs Sustained ventricular tachycardia Ibutilide is specifically indicated only for treatment of recent-onset atrial fibrillation and flutter. Patients taking amiodarone must have baseline and serial pulmonary function tests in order to monitor for potential pulmonary toxicity.

Vaughan Williams Classification Class IV verapamil, diltiazem Calcium channel blockers Depress phase 4 depolarization Used for paroxysmal supraventricular tachycardia; rate control for atrial fibrillation and flutter

Vaughan Williams Classification Other Antidysrhythmics digoxin, adenosine Have properties of several classes and are not placed into one particular class

Antidysrhythmics Digoxin Cardiac glycoside Inhibits the sodium-potassium ATPase pump Positive inotrope—improves the strength of cardiac contraction Allows more calcium to be available for contraction Used for CHF and atrial dysrhythmias Monitor potassium levels, drug levels, and for toxicity

Antidysrhythmics adenosine (Adenocard) Slows conduction through the AV node Used to convert paroxysmal supraventricular tachycardia to sinus rhythm Very short half-life Only administered as fast IV push May cause asystole for a few seconds Other side effects minimal

Antidysrhythmics: Side Effects ALL antidysrhythmics can cause dysrhythmias!! Hypersensitivity reactions Nausea Vomiting Diarrhea Dizziness Blurred vision Headache

Antidysrhythmics: Nursing Implications Obtain a thorough drug and medical history. Measure baseline BP, P, and cardiac rhythm. Measure serum potassium levels before initiating therapy.

Antidysrhythmics: Nursing Implications Assess for conditions that may be contraindications for use of specific agents. Assess for potential drug interactions. Instruct patients regarding dosing schedules and side effects to report to physician.

Antidysrhythmics: Nursing Implications During therapy, monitor cardiac rhythm, heart rate, BP, general well-being, skin color, temperature, heart and breath sounds. Assess plasma drug levels as indicated. Monitor for toxic effects.

Antidysrhythmics: Nursing Implications Instruct patients to take medications as scheduled and not to skip doses or double up for missed doses. Patients who miss a dose should contact their physician for instructions if a dose is missed. Instruct patients not to crush or chew any oral sustained-release preparations.

Antidysrhythmics: Nursing Implications For class I agents, monitor ECG for QT intervals prolonged more than 50%. IV infusions should be administered with an IV pump.

Antidysrhythmics: Nursing Implications Patients taking propranolol, digoxin, and other agents should be taught how to take their own radial pulse for 1 full minute, and to notify their physician if the pulse is less than 60 beats/minute before taking the next dose of medication.

Antidysrhythmics: Nursing Implications Monitor for therapeutic response: Decreased BP in hypertensive patients Decreased edema Regular pulse rate or Pulse rate without major irregularities, or Improved regularity of rhythm