Chapter 40: Cardiac Glycosides, Antianginals, and Antidysrhythmics

Foundations of the Cardiovascular System

• Systemic Overview: The cardiovascular system consists of the heart, blood vessels (arteries, arterioles, capillaries, venules, and veins), and blood flow.

• Arterial and Capillary Function: Oxygen ($O_2$), nutrients, and hormones move through arteries, which narrow to arterioles and then to microscopic capillaries. Capillaries facilitate the exchange of nutrients for waste products, including carbon dioxide ($CO_2$), urea, creatinine, and ammonia.

• Venous Return: Deoxygenated blood returns to the heart via venules and larger veins, eventually being processed by the lungs (gas exchange) and kidneys (waste elimination).

• Heart Anatomy:

  • Chambers: Four chambers including the right atrium (receives deoxygenated blood), right ventricle (pumps to the pulmonary artery), left atrium (receives oxygenated blood), and left ventricle (pumps to the aorta for systemic circulation).

  • Musculature (Myocardium): The myocardium is the heart muscle surrounding chambers. The left ventricle has significantly thicker walls compared to the right, generating the force necessary for systemic circulation.

  • Membranes:

    • Pericardium: A fibrous outer covering that protects against injury and infection.

    • Endocardium: A three-layered membrane lining the inner heart chambers.

  • Valves: Control unidirectional blood flow.

    • Atrioventricular: Tricuspid and Mitral.

    • Semilunar: Pulmonic and Aortic.

• Coronary Circulation:

  • Right Coronary Artery: Supplies the right atrium and both ventricles.

  • Left Coronary Artery: Divides into the left circumflex and anterior descending arteries to supply the left atrium and both ventricles.

  • Clinical Note: Blockage in these arteries leads to myocardial infarction (MI).

Hemodynamics and Circulatory Physiology

• Electrical Conduction:

  • Sinoatrial (SA) Node: Located in the posterior wall of the right atrium; known as the "pacemaker." Normal adult rate is $60-80\,beats/min$.

  • Atrioventricular (AV) Node: Located in the posterior right side of the interatrial septum. Inherent rate is $40-60\,beats/min$.

  • Bundle of His (AV Bundle): A continuous tract of fibers from the AV node.

  • Backup Mechanism: If the SA node fails, the AV node assumes the pacemaker role at a slower rate. Ventricles can contract independently at $30-40\,beats/min$.

• Regulation Mechanisms:

  • Sympathetic Nervous System: Increases heart rate via stimulation.

  • Parasympathetic Nervous System: Decreases heart rate via stimulation.

• Hemodynamic Calculations:

  • Cardiac Output (CO): The volume of blood expelled by the heart in 1 minute. Formula: $CO = HR \times SV$. Average range: $4-8\,L/min$.

  • Stroke Volume (SV): Amount of blood ejected per beat. Average is $\approx 70\,mL/beat$.

• Determinants of Stroke Volume:

  • Preload: The blood flow force stretching the ventricle at the end of diastole. Higher preload generally increases SV.

  • Contractility: The force of the ventricular contraction.

  • Afterload: Resistance to ventricular ejection caused by opposing pressures in the aorta and systemic circulation. If afterload increases, SV decreases.

• Blood Composition:

  • Plasma: 55% of volume; contains 90% water and 10% solutes (glucose, lipids, electrolytes, minerals, enzymes, etc.).

  • Red Blood Cells (RBCs/Erythrocytes): Carry oxygen on hemoglobin. Life span: $\approx 120\,days$.

  • White Blood Cells (WBCs/Leukocytes): Body defense and antibody production. Life span: $2-24\,hours$.

  • Platelets: Facilitate blood coagulation.

Heart Failure: Pathophysiology and Diagnostics

• Definition: Heart failure (HF), or pump failure, occurs when the myocardium weakens and enlarges, losing the ability to pump blood into systemic circulation.

• Classification:

  • Left-Sided HF: Left ventricle fails to pump blood from the lungs/left atrium into the aorta. Results in blood backing up into lung tissue, causing shortness of breath (SOB) and dyspnea.

  • Right-Sided HF: Heart fails to pump blood returned from systemic circulation. Results in peripheral edema.

  • Relationship: Left-sided failure often leads to right-sided failure.

• Physiological Changes: Myocardial hypertrophy (cardiomegaly) and increased preload/afterload.

• ACCF/AHA Staging:

  • Stage A: High risk for HF, no structural disease or symptoms.

  • Stage B: Structural heart disease present, but no signs or symptoms.

  • Stage C: Structural disease with prior or current symptoms.

  • Stage D: Refractory HF requiring specialized interventions.

• Laboratory Tests:

  • Atrial Natriuretic Hormone/Peptide (ANH/ANP): Released during atrial expansion; acts against renin/aldosterone. Reference values: $20-77\,pg/mL$ ($20-77\,ng/L$).

  • Brain Natriuretic Peptide (BNP): Secreted from atrial cardiac cells; primary HF diagnostic tool.

    • Desired Value: $< 100\,pg/mL$.

    • Positive/HF Value: $> 100\,pg/mL$; in severe HF, values may be markedly higher (e.g., $400-1000\,pg/mL$).

    • Sensitivity: More sensitive than ANP and helps differentiate HF from lung dysfunction in patients with dyspnea.

Cardiac Glycosides: Digoxin

• Source: Purple and white foxglove plant (Digitalis).

• Primary Drug: Digoxin.

• Mechanisms of Action (Triple Effect):

  1. Positive Inotropic: Increases myocardial contraction force and stroke volume.

  2. Negative Chronotropic: Decreases heart rate.

  3. Negative Dromotropic: Decreases conduction of heart cells.

• Physiological outcomes: Improved cardiac output, decreased preload, enhanced peripheral/kidney perfusion, decreased edema, and promoted fluid excretion.

• Pharmacokinetics:

  • Absorption: PO tablets ($60\%-80\%$); PO liquid ($70\%-85\%$).

  • Distribution: Protein binding: $25\%$.

  • Metabolism/Excretion: Half-life is $36-48\,hours$. Accumulation can occur. $13\%-16\%$ liver metabolism; $70\%$ kidney excretion (mostly unchanged).

  • Routes: PO and IV.

• Narrow Therapeutic Index (NTI): Requires careful titration and monitoring.

  • Therapeutic Range for Dysrhythmias: $0.8-2.0\,ng/mL$.

  • Target Level for HF: $0.5-1.0\,ng/mL$.

• Contraindications and Cautions:

  • Absolute: Ventricular fibrillation hypersensitivity.

  • Caution: AMI, AV block, renal/hepatic dysfunction, bradycardia, hypokalemia.

• Thyroid influence: Hypothyroidism requires dose decreases; hyperthyroidism may require dose increases.

• Digitalis (Digoxin) Toxicity:

  • Symptoms: Anorexia, nausea, vomiting, diarrhea, bradycardia ($< 60\,beats/min$), premature ventricular contractions (PVCs), visual illusions (white, green, or yellow halos), confusion, and delirium.

  • Antidote: Digoxin-immune Fab. Binds with digoxin to form complex molecules for urinary excretion.

  • Interactions: Potent diuretics (furosemide/hydrochlorothiazide) cause hypokalemia, increasing the risk of toxicity.

Emerging and Alternative Heart Failure Therapies

• Phosphodiesterase (PDE) Inhibitors:

  • Prototype: Milrinone lactate.

  • Mechanism: Inhibits PDE, promoting positive inotropic response and vasodilation.

  • Use: Short-term (48-72 hours) for acute decompensated HF.

  • Risks: High-alert drug; can cause severe dysrhythmias and thrombocytopenia.

• Guanylate Cyclase Stimulant:

  • Prototype: Vericiguat.

  • Mechanism: Regulates vascular tone and cardiac remodeling.

  • Contraindication: Pregnancy (Serious Birth Defects).

• Sodium-Glucose Co-Transporter (SGLT) Inhibitors:

  • SGLT2 Inhibitors: Empagliflozin ($10\,mg\,PO\,daily$), Dapagliflozin ($5-10\,mg\,PO\,daily$).

  • Dual SGLT1/SGLT2 Inhibitor: Sotagliflozin ($200-400\,mg\,PO\,daily$).

  • Benefit: Significant reduction in CV death and HF hospitalizations.

• Nonpharmacologic Measures:

  • Salt intake: Limit to $2\,g/day$ ($\approx 1\,tsp$).

  • Alcohol: Avoid or limit to 1 drink/day.

  • Activity: Mild exercise (walking/bicycling) recommended.

Angina Pectoris: Types and Antianginal Drugs

• Definitions: Pain caused by inadequate blood flow and oxygen supply to the myocardium.

• Classification:

  1. Classic (Stable): Predictable stress or exertion.

  2. Unstable (Preinfarction): Unpredictable, occurring with progressive severity unrelated to activity; indicates impending MI.

  3. Variant (Prinzmetal/Vasospastic): Occurs at rest due to vessel spasm.

• Nitrates: First-line for angina.

  • Nitroglycerin: Causes generalized vascular and coronary vasodilation.

  • Sublingual (SL): Absorption under the tongue. Max dose: 3 tablets ($300-600\,mcg$) within 15 minutes. If pain persists, call 911.

  • Patch/Ointment: Requires a nitrate-free interval of $8-12\,hours$ (usually overnight) to prevent tolerance.

  • Side Effects: Most common is headache; others include hypotension, dizziness, and reflex tachycardia.

• Beta-Blockers: Decrease sympathetic nervous system effects (catecholamines like epinephrine/norepinephrine).

  • Selective (Beta1): Atenolol, Metoprolol. Preferred for angina as they avoid bronchoconstriction.

  • Use: Most effective for Classic (Stable) angina.

  • Contraindications: Bradycardia, second/third-degree AV block.

• Calcium Channel Blockers (CCB):

  • Prototype: Verapamil, Nifedipine, Diltiazem.

  • Action: Relax coronary artery spasms (Variant) and peripheral arterioles (Stable).

  • Nifedipine Warning: Immediate-release forms reached an association with increased sudden cardiac death; sustained-release is preferred.

Cardiac Dysrhythmias and Antidysrhythmic Drugs

• Dysrhythmias: Deviations from normal rate (Tachycardia, Bradycardia, or Irregular).

• Action Potentials (Phases):

  • Phase 0: Rapid depolarization (Sodium influx).

  • Phase 2: Plateau (Calcium influx).

  • Phase 3: Rapid repolarization (Potassium efflux).

• Antidysrhythmic Classes:

  • Class I: Sodium Channel Blockers:

    • IA: Slow conduction, prolong repolarization (Quinidine, Procainamide).

    • IB: Slow conduction, shorten repolarization (Lidocaine, Mexiletine).

    • IC: Prolong conduction, no effect on repolarization (Flecainide, Propafenone).

  • Class II: Beta-Blockers: Decrease conduction velocity and automaticity (Propranolol, Acebutolol, Esmolol).

  • Class III: Drugs that Prolong Repolarization: Emergency treatment. Amiodarone increases refractory period.

    • Amiodarone Warnings: Can cause liver toxicity, lung toxicity, and iodine hypersensitivity.

  • Class IV: Calcium Channel Blockers: Block calcium influx, decreasing excitability and contractility (Verapamil, Diltiazem).

• Miscellaneous Agents:

  • Adenosine: Used for life-threatening VT/VF. Half-life is $< 10\,seconds$.

Clinical Judgment and Nursing Process

• Recognizing Cues (Assessment):

  • Obtain apical pulse for 1 full minute. If HR $< 60\,beats/min$, withhold Digoxin and notify provider.

  • Check serum potassium (normal $3.5-5.0\,mEq/L$) and Digoxin (normal $0.8-2\,ng/mL$) levels.

  • Identify herbal drug interactions:

    • Ginseng: Falsely elevates digoxin levels.

    • Licorice: Promotes hypokalemia, increasing digitalis toxicity risk.

    • St. John's Wort: Decreases digoxin levels.

• Nursing Interventions:

  • Position patient sitting or lying during initial nitrate administration to prevent orthostatic hypotension.

  • Apply nitroglycerin topical forms using gloves; do not touch medication with fingers.

  • A stinging sensation indicates freshness in some SL nitroglycerin tablets.

• Patient Education:

  • Explain the importance of reporting blurred/yellow vision (toxicity).

  • Advise to avoid alcohol, caffeine, and tobacco (vasoconstriction/hypotension effects).

  • Dietary: Encourage foods high in potassium (fresh/dried fruits, fruit juices, potatoes) when taking potassium-wasting diuretics.

Questions & Discussion

• Why must I count my pulse before Digoxin?: If the pulse is less than $60\,beats/min$, the drug must be held to avoid further depressing the heart rate, and the provider must be notified.

• What was the intervention for the case study patient?: The patient had a BNP of $1000\,pg/mL$, a potassium of $3.0\,mEq/L$, and a digoxin level of $3\,ng/mL$.

  • Priority actions: Administer Digoxin-immune Fab and replace potassium via IV saline transition.

  • Refusal of KCl: The patient had poor compliance because "it makes me sick," highlighting the need for education on toxicity risk and compliance.

• Side effect of initial Nitrate dose: Headaches are expected and commonly treated with Acetaminophen.

• Discontinuing Beta-Blockers: They must never be stopped abruptly; doses must be tapered to prevent reflex tachycardia and life-threatening dysrhythmias.