Unit 4: Introduction to Cardiovascular System Drug Therapy

Heart Anatomy and Blood Vessels

• Four Chambers and Layers of the Heart

  • Atria

  • Ventricles

  • Endocardium

  • Myocardium

  • Pericardium

• Types of Blood Vessels

  • Arteries: Carry oxygenated ($O_2$) blood away from the heart.

  • Capillaries: Microscopic vessels for exchange.

  • Veins: Carry deoxygenated (de$O_2$) blood toward the heart; contain valves to prevent backflow.

  • Exceptions: The pulmonary arteries carry deoxygenated blood, and pulmonary veins carry oxygenated blood.

• Coronary Arteries: Supply blood directly to the heart muscle itself.

• Key Anatomical Structures (Numbered List from Chabner Text)

  1. Superior vena cava

  2. Inferior vena cava

  3. Right atrium

  4. Tricuspid valve

  5. Right ventricle

  6. Pulmonary valve

  7. Pulmonary artery

  8. Pulmonary veins

  9. Left atrium

  10. Mitral valve

  11. Left ventricle

  12. Aortic valve

  13. Aorta

Blood Flow Pathway

• Step-by-Step Systemic and Pulmonary Circulation

  • Venae cavae (carrying de$O_2$ blood) → Right atrium (RA) → tricuspid valve → Right ventricle (RV) → pulmonary artery → lung capillaries.

  • In the Lungs: Carbon dioxide ($CO_2$) is "blown off" and oxygen ($O_2$) is obtained.

  • Returning to the Heart: Pulmonary veins → Left atrium (LA) → mitral valve → Left ventricle (LV) → aortic valve → aorta.

  • Systemic Distribution: Arteries → arterioles → tissue capillaries.

  • In the Tissues: $O_2$ leaves the blood and enters cells; the blood picks up $CO_2$.

  • Returning to Venae Cavae: Venules → veins → back to the venae cavae.

• Sequential Descriptions from Hitner Text

  1. Blood enters the right atrium from the superior and inferior venae cavae.

  2. Blood in the right atrium flows through the right AV (tricuspid) valve into the right ventricle.

  3. Contraction of the right ventricle forces the pulmonary valve open.

  4. Blood flows through the pulmonary valve into the pulmonary trunk.

  5. Blood is distributed by right and left pulmonary arteries to the lungs for gas exchange (unload $CO_2$, load $O_2$).

  6. Blood returns via pulmonary veins to the left atrium.

  7. Blood in the left atrium flows through the left AV (bicuspid/mitral) valve into the left ventricle.

  8. Contraction of the left ventricle (simultaneous with step 3) forces the aortic valve open.

  9. Blood flows through the aortic valve into the ascending aorta.

  10. Blood in the aorta is distributed to every organ in the body.

  11. Blood returns to the heart via the venae cavae.

Heartbeat Mechanics: Systole and Diastole

• Systole (Contraction Phase)

  • The right and left ventricles (RV and LV) contract.

  • Blood is pumped into the pulmonary artery and the aorta.

  • The mitral and tricuspid valves remain closed to prevent backflow into the atria.

• Diastole (Relaxation and Filling Phase)

  • The ventricle walls relax.

  • Blood enters the heart from the venae cavae and pulmonary veins.

  • The tricuspid and mitral valves open.

  • Blood flows from the RA and LA into the ventricles.

  • The pulmonary and aortic valves are closed.

Important Electrolytes

• Sodium ($Na^+$)

  • Main extracellular electrolyte.

  • Responsible for fluid balance.

• Potassium ($K^+$)

  • Main intracellular electrolyte.

  • Maintains cell structure and function, especially within cardiac muscle.

• Calcium ($Ca^{++}$)

  • Mineral associated with bone health.

  • Aids in muscle contraction and blood coagulation.

  • Associated with Force of Contraction (FOC).

Cardiac Conduction System

• Electrical Pathway Components

  • Sinoatrial (SA) node: Located in the Right Atrium; known as the pacemaker. Impulse starts here.

  • Autorhythmicity: The heart’s ability to initiate its own electrical impulse.

  • Atrioventricular (AV) node: Receives the impulse from the SA node.

  • Atrioventricular Bundle (Bundle of His): Conducts impulse through the interventricular septum.

  • Left and Right Bundle Branches: Division of the bundle of His heading toward the apex.

  • Purkinje Fibers (Conduction myofibers): Distribute excitation through the ventricular myocardium.

• Action Potential: The electrical impulse carried from the SA node to the ventricular walls, causing contraction.

• Monitoring: The conduction system is monitored via an EKG/ECG (electrocardiogram).

Phases of the Cardiac Action Potential

• Phase 4 (Resting Membrane Potential): Corresponds to diastole. $Na^+$ is outside the cell and $K^+$ is inside.

• Phase 0 (Rapid Depolarization): $Na^+$ channels open. $Na^+$ rapidly moves into the cell, reversing membrane potential and generating an action potential.

• Phases 1, 2, and beginning of 3: $K^+$ moves to the outside of the cell to return the membrane potential to resting level (repolarization).

  • Refractory Period: The period where the cell cannot receive another action potential. This prevents continuous contraction, known as tetany.

• Phase 2 (Plateau Phase): Characterized by a balance of $Ca^{++}$ moving inside the cell and $K^+$ moving out. This phase is responsible for muscle contraction.

• Phase 3 (Rapid Repolarization): $Ca^{++}$ channels close and more $K^+$ channels open.

• Phase 4 (Repetition): Slow inward movement of $Na^+$ and $Ca^{++}$ and outward movement of $K^+$ excites the membrane to cause another depolarization.

EKG/ECG Components and Interpretation

• P wave: Reflects atrial depolarization ($Na^+$ ions enter the cell; the inside becomes less negative/more positive).

• PR wave segment: Reflects the duration for the nerve impulse to travel from the SA node to the AV node.

• QRS wave: Reflects ventricular depolarization and atrial repolarization (impulse moving from AV node through Purkinje fibers).

• ST segment: Corresponds to the absolute refractory period where cells cannot be stimulated to contract (prevents tetany).

• T wave: Reflects ventricular repolarization. Resting potential is restored, and $Na^+$ and $K^+$ are pumped back to starting positions.

• EKG Measurements and Timing

  • Voltage: $10\,mm/mV$.

  • Time/Paper Speed: $25\,mm/sec$.

  • Small box height/width: $5\,mm = 0.5\,mV$.

  • Time block: $5\,mm = 0.2\,sec = 200\,msec$.

Autonomic Nervous System (ANS) Control

• Sympathetic Nerves (Fight or Flight)

  • Neurotransmitters: Norepinephrine (NE) and Epinephrine (EPI) from the adrenal medulla.

  • Positive Chronotropic Effect: Increase Heart Rate (HR).

  • Positive Inotropic Effect: Increase Force of Contraction (FOC).

  • Positive Dromotropic Effect: Increase Conduction speed.

• Parasympathetic Nerves (Rest and Digest)

  • Neurotransmitter: Acetylcholine (ACH).

  • Negative Chronotropic Effect: Decrease HR.

  • Negative Inotropic Effect: Decrease FOC.

  • Negative Dromotropic Effect: Decrease Conduction speed.

Cardiac Rhythms and Disorders

• Normal Sinus Rhythm: Normal rate, normal rhythm, accurate measurements, and no extra beats.

• Fibrillation: Characterized by quivering and ineffective contractions.

• Heart Failure (HF):

  • Can occur with activity or at rest.

  • The heart is unable to pump blood effectively; more blood enters than is pumped out.

  • Hypertrophy: Thickening of the heart muscle.

  • Decreased Organ Perfusion: Less blood reaches organs.

• Compensatory Mechanisms in Heart Failure

  • Kidneys: Retain fluid and electrolytes, leading to edema.

  • Sympathetic Nerves: Increase HR and FOC.

• Specific Types of Heart Failure

  • Left Ventricular Failure ("Pulmonary Congestion"): Symptoms include Dyspnea, Orthopnea, Tachypnea, Pulmonary edema, Coughing, and Nocturnal dyspnea.

  • Right Ventricular Failure ("Venous Congestion"): Symptoms include Pitting edema, Ascites (fluid in abdominal cavity), and edema in hands and feet.

Pharmacological Actions of Cardiac Drugs

• Inotropic (Force of Contraction - FOC)

  • Positive Inotropic: Increases FOC (Example: Cardiac glycosides).

  • Negative Inotropic: Decreases FOC (Examples: Beta Blockers, Calcium Channel Blockers).

• Chronotropic (Rate - beats/min)

  • Positive Chronotropic: Increases HR (Examples: Epinephrine, Atropine).

  • Negative Chronotropic: Decreases HR (Example: Cardiac glycosides).

• Dromotropic (Conduction)

  • Positive Dromotropic: Increases conduction.

  • Negative Dromotropic: Decreases conduction.

Cardiac Glycosides

• Mechanism of Action (MOA)

  • Decreases heart rate and slows conduction through the AV node.

  • Increases force of contraction by accelerating the entry of $Ca^{++}$ into cardiac muscle cells.

  • Increases kidney function by adding blood flow, which eliminates excess fluid/electrolytes to treat edema.

  • Interferes with the $Na^+/K^+$ pump.

• Primary Drug: digoxin (Lanoxin®)

• Uses: Congestive Heart Failure (CHF) and Arrhythmias (Atrial fibrillation, Atrial tachycardia).

• Therapeutic Serum Level: $0.5$ to $2\,ng/ml$.

• Toxic Level: $>2.5\,ng/ml$.

• Toxicity Risks and Symptoms

  • Increased risk with hypercalcemia and hypokalemia.

  • Cardiac Symptoms: Slow pulse or irregular pulse.

  • CNS Symptoms: Confusion, headache (HA), delirium, visual changes (Halos around dark objects).

  • GI Symptoms: Nausea, vomiting, diarrhea (NVD).

• Toxicity Treatment: Administer $K^+$ to strengthen contraction, discontinue (d/c) the drug, monitor serum levels.

  • Antidote: digoxin immune fab.

• Patient Care: Check pulse for $60-100\,bpm$ prior to administration. Conduct digitalization and maintenance dosing.

Vasodilators and Nitrates

• Preload: The extent to which the chamber is stretched prior to contraction (venous return).

• Afterload: The tension required to cause a contraction (resistance from arteries).

• Nitrate MOA: Dilates smooth muscle in vessels to decrease venous return, decrease BP, and decrease cardiac workload.

• Clinical Effects: Dilate veins and arteries to decrease BP, decrease preload and afterload, decrease work on the heart, and decrease oxygen demand while increasing cardiac output.

• Nitrate Side Effects and Teaching

  • Headaches, faintness, lightheadedness, tachycardia, orthostatic hypotension (caution with position changes).

  • Drug Interactions: Severe hypotension if taken with Erectile Dysfunction (ED) meds.

  • Storage: Do not expose to light or air; drug loses potency.

  • Angina Protocol: Take 1 tablet every 5 minutes for up to 3 doses; seek immediate medical attention if unresolved.

• Nitroglycerin Transdermal System: Common dosage $0.4\,mg/hr$.

Inadequate Oxygenation Compensation

• Brain Effects: Dizziness, drowsiness, decreased alertness.

• Lung Effects: Shortness of breath (SOB), coughing.

• Kidney Compensation: Retention of $H_2O$ and electrolytes leads to systemic and pulmonary edema. Diuretics are required to eliminate fluid.

Beta Blockers

• Mechanism of Action (MOA)

  • Reverse excessive sympathetic activation of beta-1 receptors.

  • Blocks beta-1 receptors to decrease HR, decrease FOC, and decrease oxygen consumption.

  • Non-selective beta blockers also block beta-2 receptors.

• Uses: Coronary Artery Disease (CAD), angina, CHF, HTN, arrhythmias (tachycardia), migraines, glaucoma.

• Side Effects and Teaching

  • Drowsiness, GI upset, CNS depression, bradycardia.

  • Monitor serum lipid levels and glucose levels in diabetics.

  • Asthma Warning: Avoid non-selective Beta Blockers in asthma patients due to risk of bronchoconstriction.

• Drug Examples: Propranolol ($10\,mg$), Carvedilol (Coreg, $12.5\,mg$).

Coronary Artery Disease (CAD) and Angina

• Definitions

  • Arteriosclerosis: Hardening or narrowing of coronary arteries due to aging.

  • Atherosclerosis: Accumulation of fatty deposits/plaque in arterial walls.

  • Ischemia: Occurs when oxygen demand exceeds supply due to blockage.

  • Angina Pectoris: Chest pain caused by insufficient blood flow.

• Types of Angina

  1. Exertional/Stable Classic Angina: Chest pain occurring with activity or stress; usually resolves with rest or meds.

  2. Unstable Angina: Unpredictable bouts occurring at rest; does not respond to rest; often a precursor to Myocardial Infarction (MI).

  3. Prinzmetal (Vasospasm): Sudden constriction of the coronary artery causing chest pain.

Calcium Channel Blockers (CCBs)

• Overview: Also known as Calcium Antagonists. Do not use with CHF patients due to existing ineffective pumping.

• 1. Dihydropyridines (e.g., for Angina, HTN)

  • Vasodilating effect MOA:

    1. Block calcium entry into cardiac muscle (decrease FOC/O2 demand).

    2. Block calcium entry into smooth muscles (vasodilation, decrease BP).

• 2. Nondihydropyridines (e.g., for Angina, HTN, Tachyarrhythmias)

  • MOA:

    1. Block calcium at SA and AV nodes (decrease SA rate and AV conduction velocity).

    2. Block calcium in cardiac muscle (decrease FOC).

    3. Block calcium in smooth muscle (vasodilation).

• Side Effects: Headache (HA), facial flushing, dizziness, hypotension, reflex tachycardia, constipation, xerostomia.

• Drug Interactions: Concerns with polypharmacy (e.g., CCB plus a Beta Blocker). Combining them can significantly depress cardiac activity and lead to CHF.

Myocardial Infarction (MI)

• Definition: Heart attack resulting from insufficient blood flow leading to tissue injury (ischemia), necrosis (deadened tissue), and an infarct (scarring).

• Statistics

  • #1 killer in the U.S.

  • One MI occurs every 20 seconds.

  • One MI death occurs every minute.

  • Approximately 697,000 annual deaths (1 in every 5 deaths).

• Treatment Protocols

  • Pain and anxiety control.

  • Oxygen support.

  • Nitroglycerin (improves blood flow to heart muscle).

  • Aspirin or anticoagulant therapy (reduces stroke risk).

  • Surgical intervention (cath lab, stents, bypass/CABG) to determine and fix blockages.

  • Beta Blockers (reduce sympathetic activity and workload).

  • BP and cholesterol lowering medications.

  • Rest for healing.

  • Patient Teaching: Use stool softeners to prevent the vasovagal response during strain.