PHARMACOLOGY OF CARDIOVASCULAR SYSTEM

Dr Ebtehal El-Demerdash
Assist. Prof. of Pharmacology & Toxicology Faculty of Pharmacy, Ain Shms University

Overview
Introduction Drugs used for treatment of:
Hypertension Angina Arrhythmia Heart failure

CVS consists of: - HEART - BV - BLOOD It is a closed system inside which blood circulates CIRCULATORY SYSTEM

The Cardiovascular System

Major function is transportation Blood is the vehicle (Rides on vessels) Oxygen, nutrients, wastes, hormones, etc. are the passengers

FORCE OF HEART

General function of circulatory system

Respiratory Nutritional Excretory Endocrinal Body temperature regulation

Homeostasis

Heart Anatomy
location Located within mediastinum, the medial cavity of the thorax

heart muscle = myocardium

atrial mass ventricular mass

Heart Coverage
Enclosed by Pericardium 3 Layers
Outer-Epicardium
(thin cover)

Middle-Myocardium
(thick, ringlike, contractile)

Inner-Endocardium
(thin sheet between chambers)

Functions of Atria and Ventricles

The Atria: - Blood receptacles
- Pump action - Venous return sensor - Endocrinal function

The Ventricles - The true pump

Four Valves
The Right Atrioventricular Valve (right A-V valve); Tricuspide valve The Left Atrioventricular Valve (left A-V valve); Mitral valve The Pulmonic Valve The ortic Vlave

The Conducting System

The Nodal System
Sinoatrial Node (S-A node) 1 Atrioventricular Node (A-V node) 3

The Internodal System

Anterior, Middle & Posterior 2 Bachmann`s bundle 7

The Purkinje System

Atrioventricular bundle (bundle of His) 4 Right & left bundle branch 5 Purkinje fibers 6

Circulation of Blood
We have two circulations Systemic & Pulmonary

Definitions
Systole: contraction of cardiac muscle Diastole: relaxation of cardiac muscle Heart rate (HR): number of heart beats/min (~ 75beats/min) Tachycardia: HR above 100beats/min Bradycardia: HR below 60beats/min Cardiac output (CO): total volume of blood pumped by each
ventricle/min

Ventricular Volumes
THE END-DIASTOLIC VOLUME(EDS): THE END-SYSTOLIC VOLUME (ESV): THE STROKE VOLUME (SV):
Volume of blood in the ventricle at the end of diastole

Volume of blood in the ventricle at the end of systole

Volume of blood pumped by the ventricle per beat SV = EDV (135ml) ESV (65ml) = 70ml CO = SV x HR = 70 x 70 ~ 5L/min

Properties of Cardiac Muscle

Autorhythmicity Excitability

Conductivity

Contractility

Autorhythmicity
independent of extrinsic stimuli regular cycle

Automaticity: ability of the heart to beat Rhythmicity: ability of the heart to beat in Autorhythmicity: ability of the heart to
beat regularly stimuli independent on extrinsic

rate

Chronotropism: an influence on the heart

Pacemaker
SA-node Primary pacemaker 105 impulse/min Sinus rhythm AV-node Secondary pacemaker 45-60 impulse/min Nodal rhythm

Inhibitory vagal tone

Purkinje System Tertiary pacemaker 25-40 impulse/min Idioventricular rhythm

Pacemaker Potential

Ectopic foci Sick Sinus syndrome

Excitability
Excitability: ability of the heart to
respond to stimuli

Bathmotropism: an influence on
myocardial excitability

Contractile myocardium action potential

Phase 0: rapid depolarization due
to rapid Na+ influx

Phase 1: early partial repolarization

due to CL- influx and limited K+ efflux plateau prolonged depolarization due to Ca2+ influx through slow Ca channels 2+) (depolarizing Ca

Phase

2:

Phase 3: repolarization due to K+

efflux without Ca2+ influx Na+/K+ pump

Phase 4: complete repolarization by

Inward going Rectefication

The absolute refractory period (ARP): The ventricles can not

respond to any stimuli to strong stimuli

The relative refractory period (RRP): The ventricles can respond Supernormal phase excitability (SNP): The Arrhythmia:
abnormal rhythm of heart beats heart

of
or

respond to weaker stimuli

rate

Conductivity
between cardiac muscle fibers conductivity

Conductivity: transmission of impulses Dromotropism: an influence on the

Charatcters of A-V node

the artia finish their systole before starting the ventricular systole

Very slow conductivity: so

Long absolute refractory period: limits the number of

impulses that reach the ventricles (230 impulse/min) failure of conduction of impulses from SA node down to the ventricles

Heart

block:

Types of Heart Block

Sinoatrial block (SA block)
No P-wave

Atrioventricular block (AV block)

1st degree (prolonged AV conduction) so PR interval is long 2nd degree (regular & irregular) 3rd degree Right or left

Bundle-branch block Physiological 2nd degree heart block

Contractility
muscle to change the potential energy of the food to mechanical energy contractility

Contractility: ability of the myocardial

Ionotropism: an influence on the

Types of Ca2+ transport across the sarcolemma

Transient (T-type) Ca channels:
They are present in the nodal and conducting system only They are activated (open) at a threshold membrane potential of 60 mV and deactivated rapidly (close) They are not affected by -stmiulant and Ca channel blockers

Long lasting (L-type) Ca channels:

They are present in all myocardial cells They are activated at threshold membrane potential of 45 mV and deactivated slowly They are activated by -stmiulant and blocked by Ca channel blockers

Types of Ca2+ transport across the sarcolemma (cont.)

Ca pump:
This is one-way pump found in the sarcolemma and pumps Ca2+ out of the myocardial cells It is an ATPase that gets the energy for pumping by hydrolysis of ATP It has high affinity but low capacity of Ca2+ transport

Na+/Ca2+ exchanger:
This is an antiport carrier in the sarcolemma It exchanges Na+ at one side with Ca2+ on the other The direction depends on ion concentration on both sides

Mechanism of Contraction
Two types of proteins Relaxation Proteins:
Troponin Tropomyocin

Contraction proteins:
Actin Myosin

Role of Ca++ in Cardiac and Smooth Muscle In cardiac muscle, Ca++ binding to troponin C relieves troponin inhibition of actin-myosin interactions In smooth muscle, Ca++ binding to calmodulin activates myosin light chain kinase which in turn phosphorylates the Plight chain of myosin and triggers contraction (i.e. actin-myosin interactions)

ANS Control of Heart

Cardiac Properties Parasympathetic (Vagal) Supplies the atria, SA node, AV node & AV bundle but not the ventricles Rhythmicity Excitability AV conduction Contractility Rate of O2 consumption Slowing due to depression of SA node (heart block) Depressed in atria Sympathetic Supplies all cardiac tissue including the ventricles Acceleration due to of SA node Stimulated in atria and ventricles

What is the Electrocardiogram?

Electrocardiogram (ECG)
P: atrial depolarization
(atrial systole)

QRS: ventricular T: ventricular

depolarization (ventricular systole)

repolarization (ventricular diastole)

PR interval: represents

the rate of A-V conduction the duration of ventricular systole

QS interval: represents

Which are the principle effects of stimulation of sympathetic nerve to the heart?
a- Activation of 1adrenoceptors c- Increased contractile force d- Decreased automaticity e- Facilitation of AV conduction b- Increased heart rate