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Principles of Pharmacology - Week 10 Seminar Notes

Topic = Cardiovascular Pharmacology

Overview of Cardiovascular Pharmacology

  • Week 10 focus: Cardiovascular pharmacology

  • Key topics:

    • Revision of cardiac anatomy and physiology

    • Principles of drug action for managing cardiovascular conditions

    • Specific conditions:

    • Hypertension

    • Angina

    • Arrhythmias

    • Heart failure

    • Blood clotting disorders

Cardiac Anatomy and Physiology

Structure of the Heart

  • The heart is a muscular organ responsible for pumping blood through the circulatory system,
    which carries oxygenated blood to tissues and organs.

  • Three functional parts of the heart:

    1. Cardiac muscle

    2. Conduction system

    3. Nerve supply.

Blood Flow Through the Heart

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

  2. Flow through right AV valve into the right ventricle.

  3. Contraction of right ventricle forces pulmonary valve open.

  4. Flow through pulmonary valve into pulmonary trunk.

  5. Distribution by right/left pulmonary arteries to lungs for gas exchange (unloading CO₂, loading O₂).

  6. Return from lungs via pulmonary veins to left atrium.

  7. Flow through left AV valve into left ventricle.

  8. Contraction of left ventricle forces aortic valve open.

  9. Flow through aortic valve into the ascending aorta.

  10. Aorta distributes blood to all organs, unloading O₂ and loading CO₂.

  11. Return to right atrium via venae cavae.

Preload and Afterload

  • Preload:

    • Definition: Initial stretching of cardiac muscle fibers before contraction.

    • Determined by volume of blood returning to the heart during diastole (ventricular filling).

    • Influenced by factors like blood volume, venous return, and atrial contraction.

  • Afterload:

    • Definition: Resistance the heart must overcome to eject blood during systole.

    • Reflects the pressure against which the ventricles pump blood into systemic/pulmonary circulation.

    • Influenced by peripheral vascular resistance and arteriolar tone.

    • Increased afterload raises cardiac workload.

Cardiac Muscle (Myocardium)

  • Responsible for heart pumping.

  • Divided into four chambers: left and right atria, left and right ventricles.

  • Contraction leads to pressure increase, forcing blood out of the heart.

  • Contraction linked to increased intracellular calcium levels.

  • Supplied by coronary arteries branching off the aorta.

Myocardial Blood Supply

  • Coronary arteries provide arterial blood to the heart:

    • Left coronary artery: supplies left ventricle, interventricular septum, part of right ventricle (85% of blood supply).

    • Right coronary artery: supplies right atrium, right ventricle, part of left ventricle, conduction system.

Conduction System of the Heart

  • Specialized nervous tissue with autorhythmicity (capability to generate its own action potentials).

  • Components:

    • Pacemaker (SA node) contracts both atria.

    • AV node, Bundle of His, Purkinje fibers excite ventricles.

  • Coordinated contraction ensures equal blood pumping from each side.

Electrocardiogram (ECG)

  • Records electrical activity of the heart from 12 different leads.

  • Shows characteristic waveforms with normative values for segments/intervals.

  • Useful for detecting cardiac abnormalities or arrhythmias.

Autonomic Control of the Cardiovascular System

Cardiac Nerve Supply

  • Receives input from:

    • Sympathetic Nervous System (SNS):

    • Releases norepinephrine, increases heart rate (HR), AV conduction, and myocardial contractility.

    • Parasympathetic Nervous System (PNS):

    • Releases acetylcholine (ACh), decreases HR and AV conduction.

  • Sympathomimetics have positive chronotropic, dromotropic, and inotropic effects via β1 adrenergic receptors.

  • Parasympathomimetics exhibit negative chronotropic and dromotropic effects via M2 muscarinic receptors.

Congestive Heart Failure (CHF)

Definition

  • CHF is the heart's inability to pump sufficient blood, resulting in decreased cardiac output and dropping blood pressure.

Pathophysiology

  • Leads to heart enlargement due to blood accumulation in chambers.

  • Kidneys release renin, activating the renin-angiotensin-aldosterone system (RAAS), retaining sodium and water.

  • Increased blood volume triggers fluid retention and edema.

Common Causes

  • Coronary artery disease, myocardial infarction, valvular disease, cardiomyopathies, arrhythmias, and others.

Types of Heart Failure

  1. Left Ventricular Failure (LVF):

    • Fails as an effective forward pump, causing back-pressure in pulmonary circulation, leading to pulmonary edema.

  2. Right Ventricular Failure (RVF):

    • Often a reaction to LVF, causing increased resistance to pulmonary blood flow and systemic venous back-pressure, leading to peripheral edema.

Treatment of CHF

  • Aims to reduce heart workload, improve coronary blood flow, and support cardiac function without increasing oxygen demands.

Key Medications:

  • Cardiac glycosides (e.g., Digoxin):

    • Stimulate myocardial contraction (positive inotropic effect) and vagal stimulation (negative chronotropic effect).

  • Vasodilators:

    • Dilation of coronary arteries improves oxygen supply, reduces venous return and preload, lowers afterload.

  • Diuretics:

    • Reduce fluid retention and edema, decreasing pulmonary congestion and blood volume.

  • Beta-blockers:

    • Reduce myocardial sympathetic activation, heart rate, contractility, and oxygen requirements (to be used carefully).

Arrhythmias

Definition

  • Arrhythmias are abnormalities in heart rate or electrical rhythm, causing:

    • Disruption of normal atrial and ventricular activation and contraction.

    • Reduced cardiac output and blood pressure.

    • Risk of ventricular fibrillation or cardiac arrest.

Causes

  • Associated with coronary artery disease, electrolyte disturbances, myocardial infarction, etc.

Classification by Origin

  • Supraventricular Arrhythmias: Originate in the atria and AV node areas.

  • Ventricular Arrhythmias: Originate below the AV node.

Detection

  • Abnormalities are recorded via ECG, including common types such as:

    • Tachycardias

    • Premature contractions

    • Fibrillations

Hypertension

Definition

  • Hypertension signifies elevated arterial blood pressure.

Physiological Factors Influencing Blood Pressure

  1. Cardiac Output (CO):

    • Determined by heart rate (HR) and stroke volume (SV).

    • CO = HR x SV

  2. Peripheral Resistance (PR):

    • Resistance arteries and arterioles create against blood flow, increased by vasoconstriction.

Blood Pressure Measurement Categories (Adults)

Category

Systolic (mm Hg)

Diastolic (mm Hg)

Normal

<120

<80

Elevated

120-129

<80

Hypertension Stage 1

130-139

80-89

Hypertension Stage 2

≥140

≥90

Hypertensive Crisis

>180

>120

Forms of Hypertension

  • Primary (Essential) Hypertension:

    • Not attributable to any overt disease process.

  • Secondary Hypertension:

    • Results from an identifiable secondary cause.

  • Malignant Hypertension:

    • Rapidly developing high blood pressure with evidence of organ damage.

Treatment Approaches for Hypertension

  • Diuretics:

    • Increase sodium and water excretion, reducing blood volume.

    • Common types: Thiazide, Loop, Potassium-sparing diuretics.

  • Sympatholytics:

    • Includes β-blockers, acting on beta-receptors to de-increase cardiac output.

  • Vasodilators:

    • Directly dilate blood vessels, lowering blood pressure.

  • RAAS Modulators:

    • ACE inhibitors and Angiotensin Receptor Blockers (ARBs) reduce the production of angiotensin II, promoting vasodilation and lowering blood pressure.

Blood Clot Formation

Coagulation Process

  • Essential for survival, preventing blood loss and promoting wound healing.

  • Can become problematic leading to thromboembolism due to overactivity or narrowed vessels.

Treatment for Blood Clots

  • Anticoagulants:

    • Interfere with clotting factors, reducing clot formation.

  • Antiplatelet Agents:

    • Inhibit platelet aggregation to prevent clot plug formation.

  • Thrombolytics/Fibrinolytics:

    • Dissolve established clots for acute scenarios, such as myocardial infarction or stroke.

Key Anticoagulants

  • Heparins:

    • Bind to clotting factors, administered parenterally for rapid action.

  • Oral Anticoagulants (e.g., Warfarin):

    • Vitamin K antagonist, slow action, impacted by diet.

    • Direct-acting anticoagulants (DAOCs): specific factor inhibition without dietary restrictions.

Antiplatelet Drug Mechanisms

  • Aspirin:

    • Irreversibly inhibits COX, preventing thromboxane synthesis, therefore inhibiting platelet activation.

  • Clopidogrel:

    • Prevents glycoprotein IIb/IIIa activation, reducing aggregation.

Case Studies

Case Study Discussion Points

  • Understanding diagnosis and mechanisms of CHF, angina, and arrhythmias in patient cases.

  • Rationales for specific drug therapies administered to patients, including potential side effects and therapeutic goals.

  • Interpretation of ECG findings in relation to arrhythmias and understanding their clinical implications.

Conclusion

  • A firm grasp of cardiovascular pharmacology is essential for managing various cardiovascular conditions, understanding the mechanisms, treating effectively while considering patient safety and drug interactions.