Action of drugs on the cardiovascular system

the degree of tension on the muscle when it begins to con- tract, which is called the preload, * and to specify the load against which the muscle exerts its contractile force, which is called the afterload. * For cardiac contraction, the preload is usually con- sidered to be the end-diastolic pressure when the ven- tricle has become filled . * The afterload of the ventricle is the pressure in the artery leading from the ventricle.this cor- responds to the systolic pressure
Drugs and the cardiovascular system
Cardiovascular drugs are used to treat:
?Arrhythmias
?Heart failure
? Blood clotting disorders
? Ischemic heart diseases
?Hypertension
Action of drugs on the cardiovascular
system
• Drugs can alter:
? The rate and rhythm of the heart
? The force of myocardial contractility
? Peripheral resistance
? Blood volume
? Coronary arteries blood flow
Disturbances of cardiac rhythm
(arrhythmias or dysrhythmias)
Abnormality of heart rate or rhythm
• Tachycardia
?Ventricular tachycardia
? Supraventricular tachycardia
• Bradycardia
• Atrial flutter
• Atrial fibrillation
• Ventricular fibrillation
Causes of arrhythmias
• Ectopic pacemaker activity
?Damaged area of myocardium
becomes depolarised and
spontaneously active
?Latent pacemaker region activated due
to ischaemia
•dominates over SA node
Re-entry loop
• Conduction delay
Drugs affecting the rate and rhythm of
the heart
• There are 4 basic classes of antiarrhythmic
drugs.
I. Drugs that block voltage-sensitive
sodium channels
II. Antagonists of ?- adrenoreceptors
III. Drugs that block potassium channels
IIII. Drugs that block calcium channels
Drugs which block voltage-dependant
Na+ channels (class I)
• Typical example is the local anaesthetic lidocaine
• Only blocks voltage gated Na+ channels in open or inactive
state
• Dissociates rapidly in time for next AP
Lidocaine
• Is sometimes used following MI if patient shows signs of
ventricular tachycardia
? given by intravenously
• Damaged areas of myocardium may be depolarised and fire
automatically
• More Na+ channels are open in depolarised tissue
? lidocaine blocks these Na+ channels
? prevents automatic firing of depolarised ventricular tissue
• Not used prophylactically following MI
?-adrenoreceptor antagonists (class II)
• Examples: propranolol, atenolol
(Beta blockers)
•We have selective and nonselective
?- blockers
• Block sympathetic action
?act at ?1-adrenoreceptors in the
heart
?-blockers
• Used following myocardial infarction
?MI causes increased sympathetic activity
• ?-blockers prevent ventricular arrhythmias
? arrhythmias may be due to increased sympathetic
activity
• also reduce O2 demand
? reduce myocardial ischaemia
? beneficial following MI
Drugs that block K+ channels (class
III)
• Class III anti-arrhythmics
• Prolong the action potential
? mainly by blocking K+ channels
• This lengthens the absolute refractory period
• Prevents another AP occurring too soon
Drugs that block K+ channels
• Prolongs the action potential
• Not generally used because they can be also be proarrhythmic
• One exception – amiodarone
• Included as a type III anti-arrhythmic, but has other actions
in addition to blocking K+ channels
• Used to treat tachycardia associated with Wolff-Parkinson-
White syndrome (re-entry loop due to an extra conduction
pathway)
Drugs that block Ca2+ channels (class
IV)
• Example: verapamil
• Decreases slope of pacemaker action potential at
SA node
• Decreases AV nodal conduction
• Decreases force of contraction (negative
inotropy)
? Also cause some coronary and peripheral vasodilation
? The dihydropyridine Ca2+ channel blockers are not
effective in preventing arrhythmias, but do act on
vascular smooth muscle
Adenosine
• Produced endogenously
• Acts on A1 receptors at AV node
• Enhances K+ conductance
? hyperpolarises cells of conducting tissue
• Anti-arrhythmic
? Administered intravenously
?Doesn’t belong in any of the classes mentioned
Heart Failure
• What is heart failure?
? Failure of the heart to provide sufficient output
to meet the body’s requirements or demand
• Features
? Reduced force of contraction
? Reduced cardiac output
? Reduced tissue perfusion
?Oedema
Drugs used in the treatment of heart
failure
• Positive inotropic , increase cardiac output
? cardiac glycosides
? ?-adrenergic agonists
• Dobutamine
• Dopamine
• Isoprenaline
• Drugs which reduce work load of the heart
? reduce afterload and preload
Drugs which increase the force of
contraction of the heart
• Cardiac glycosides
?Have been used to treat heart failure for over
200 years
? improves symptoms but not long term
outcome
• Digoxin is the prototype
? Extracted from leaves of the foxglove digitalis
purpurea or digitalis lanata
? Blocks Na+/K+ ATPase
Action of cardiac glycosides
• Block Na+/K+ ATPase
• Increase in Na+ concentration inside the
cells leads to an inhibition of the Na+/
Ca2+ exchanger
• Increase Ca2+ concentration inside cardiac
myocytes
? Positive inotropic effect
? Increased force of contraction
Action of cardiac glycosides on heart
rate
• cardiac glycosides also cause increased
vagal activity
? action via central nervous system
? slows AV conduction
? slows the heart rate