heart Flashcards
anti-arrhythmics: recall the Vaughan-Williams classification and its limitations
3 aims of treating cardiac rhythm disturbances (arrhythmias/dysrhythmias)
reduce sudden death, prevent stroke, alleviate symptoms
5 things management of cardiac rhythm disturbances may involve
drug therapy, cardioversion, pacemakers, catheter ablation therapy, implantable defibrillators
effect on heart rate of cardiac rhythm disturbances
may increase (tachyarrhythmias) or decrease (bradyarrhythmias)
3 simple classifications of arrhythmias based on site of origin
supraventricular (usually atria), ventricular, complex (supraventricular and ventricular)
2 drugs used to treat supraventricular arrhythmias
amiodarone, verapamil
2 drugs used to treat ventricular arrhythmias
flecainide, lidocaine
drug used to treat complex arrhythmias
disopyramide
other method of classification of arrhythmias, which is of limited clinical significance
Vaughan Williams
what is Vaughan Williams classification, what are the 4 methods it distinguished between and why is it clinically limited
method of classsifying anti-arrhythmic drugs (either blocks Na+ channels, preventing depolarisation; blocks B-receptors, inhibiting muscular contraction; blocks K+ channels, preventing repolarisation; or Ca2+ channel blockers; drugs have mixed mechanisms so fall into many classes so not clinically useful
4 examples of anti-arrhythmic drug
adenosine, verapamil, amiodarone, digoxin (cardiac glycosides)
how is adenosine uses as an anti-arrhythmic drug (administration, classification of arrhythmia, length of actions vs verapamil)
IV to terminate supraventricular tachyarrhthymias; short-lived actions (20-30s), so safer than verapamil
adenosine pathway in coronary vascular smooth muscle causing relaxation
adenosine binds to adenosine type 2A (A 2A) receptors, which are coupled to Gs-protein -> Gs-protein activation -> upregulates cAMP by adenylyl cyclase -> PKA activation/myosin light chain kinase inactivation -> stimulation of K ATP channels/decreased myosin phosphorylation -> hyperpolarisation of smooth muscle/decrease in contractile force -> relaxation; adenosine also inhibits Ca2+ entry into cell through L-type Ca2+ channels
adenosine pathway in cardiac tissue causing cell hyperpolarisation and inhibition of Ca2+ entry
adenosine binds to adenosine type 1 (A 1) receptors, which are coupled to Gi-protein -> Gi-protein activation -> opening of K+ channels/decrease cAMP -> cell hyperpolarisation/inhibition of L-type Ca2+ channels and Ca2+ entry
adenosine pathway in SAN pacemaker cells causing negative chronotropy
adenosine binds to adenosine type 1 (A 1) receptors, which are coupled to Gi-protein -> Gi-protein activation -> decreases cAMP -> inhibits pacemaker current I f -> decreases slope of phase 4 of pacemaker action potential (repolarisation) -> decreases spontaneous firing rate (negative chronotropy) -> more regular heart rate as increased time do increased likelihood of regular depolarisations
use of verapamil as anti-arrhythmic drug
reduction of ventricular responsiveness to atrial arrhythmias
verapamil mechanism of action as anti-arrhythmic drug
block Ca2+ channels, so depresses SAN automatically and subsequent AVN conduction, so more regular heart rate as increased time do increased likelihood of regular depolarisations
goal of amiadarone and other anti-arrhythmic drugs
alter effective refractory period or conduction velocity, thereby hopefully abolishing reentry mechanisms
what happens in the effective refractory period
tissue is not excitable
propogation of signal across normal cardiac muscle (triangle of branch 1, 2 and 3), and in heart failure if branch 2 is dead
action potential passes down branch 1 and 2 -> moves onto other parts of cardiac muscle -> if came across each other at branch 3, cancel each other out; if dead tissue in heart failure it is unidirectional, so e.g. can’t pass down branch 2, so at branch 3 no cancelling out and works way up branch 2 to reactivate tissue, causing jerky contractions
how does the state of cardiac tissue when the action potential arrives determine whether an arrhythmia occurs
depends whether tissue can be depolarised or not (whether in effective refractory period), so sometimes jerky contractions, othertimes not
how does amiodarone prevent arrhythmias of re-entry
amiodarone has multiple ion block, including blocking K+ channels, so left in repolarisation state longer (effective refractory period), so won’t be able to depolarise as much, so chance of re-entry rhythm causing extra contractions decreases
adverse effects of amiodarone
accumulates in body, causing photosensitive skin rashes, hypo/hyper thyroidism and pulmonary fibrosis
2 conditions digoxin is used to treat as an anti-arrhythmic drug
atrial fibrillation and atrial flutter
how does digoxin exert a positive inotropic effect as an anti-arrhythmic drug
inhibits Na+/K+-ATPase pump -> Na+ can’t move out cell, so can’t be available for Na+/Ca2+ exchange -> Ca2+ remains inside cell -> increased IC Ca2+ -> positive inotropic effect
what is the effect of central vagal stimulation by digoxin
increased refractory period, reduced rate of conduction through AVN (PSNS-like effects)
how is digoxin used as an anti-arrhythmic drug when treating atrial fibrillation and flutter which lead to rapid ventricular rate, impairing ventricular filling (due to decreased filling time) and reducing cardiac output
via vagal stimulation, digoxin reduces conduction of electrical impulses within AVN, so fewer impulses reach ventricles, reducing ventricular rate so more rhythmical contractions, with more powerful contractions (positive iontropic effect, increasing cardiac output)
adverse effect of digoxin as an anti-arrhythmic drug
dysrhythmias (e.g. AV conduction block, ectopic pacemaker activity)
why does hypokalaemia (e.g. by diuretic use) lower threshold for digoxin toxicity
as digoxin targets Na+/K+-ATPase pump, K+ is competing for binding side, so if hypokalaemic, digoxin binds more easily as not as much competition
