Almost all arrhythmias are:
acquired: (MI), ischemia,
acidosis, alkalosis, electrolyte abnormalities.
Drug toxicity is a common cause of arrhythmia
cardiac Na+ channels
cardiac Ca2+ channels
cardiac K+ channels
β-adrenergic receptors (βAR)
primary targets of antiarrhythmic drugs
To date, only β-blockers have been demonstrated to reduce the incidence of_______
sudden cardiac death
Usually, catheter ablation of ectopic foci and implantable __________ are very often used in place of drugs
cardioverterdebrillator devices (ICDs)
primary targets of antiarrhythmic drugs
cardiac Na+ channels
cardiac Ca2+ channels
cardiac K+ channels
β-adrenergic receptors (βAR)
If, ICa-L, and IKs are indirect targets of antiarrhythmic drug action via
Via the β-adrenergic receptor pathway:
Prolonged QT is caused by
taking too long to repolarize, increased AP duration
Mutations in some _____ can cause a prolonged QT interval
sodium and potassium channels.
ventricular fibrillation results in a survival rate of only 40% by 5 years of
age
> 30 mutations in the cardiac Na+ channel reduce peak inward Na+ current in ventricular myocytes
Brugada syndrome
Two major sources of inappropriate impulse initiation:
a. ) ectopic foci
b. ) triggered afterdepolarizations: triggered by action potentials
an excitable group of cells that causes a premature heart beat outside the normally functioning SA node of the human heart
ectopic focus
abnormal depolarizations of cardiac myocytes that interrupt phase 2/phase 3 of the cardiac action potential in the electrical conduction system of the heart.
triggered afterdepolarizations: triggered by action potentials
Prolonged phase 2 causes excess:
Ca entry
Disturbed impulse conduction
-Reentry
Reentry factors that can be combated
- unidirectional conduction block in fx circuit
- conduction time around the circuit > refractory
Class I: blockers of voltage-gated cardiac Na+ channels
Class II: β-adrenergic receptor blockers (“β blockers”)
Class III: drugs that prolong fast response phase 2 by delaying repolarization
Class IV: blockers of voltage-gated cardiac Ca2+ channels
Vaughan Williams classification of antiarrhythmic drugs
blockers of voltage-gated cardiac Na+ channels
Vaughan Williams classification of antiarrhythmic drugs
Class I
β-adrenergic receptor blockers (“β blockers”)
Vaughan Williams classification of antiarrhythmic drugs
Class II
drugs that prolong fast response phase 2 by delaying repolarization
Vaughan Williams classification of antiarrhythmic drugs
Class III
blockers of voltage-gated cardiac Ca2+ channels
Vaughan Williams classification of antiarrhythmic drugs
Class IV
adenosine is class?
trick question, unclassified
Class Ia drugs: Na+ channel blockers
Class IA quinidine, procainamide, disopyramide
Class Ib drugs: Na+ channel blockers
Class IB lidocaine, mexiletine, phenytoin
Class Ic drugs: Na+ channel blockers
Class IC propafenone, flecainide, encainide
All class I drugs show
↑refractory period
↓ conduction velocity
↓re-entry
Re-entry can be defeated by either:
slowed conduction velocity or longer refractory period
Class Ib drugs show pure class I action:
slow upstroke, decreased AP duration
Class Ia & Class Ic drugs delay phase 3 onset via________
K+ channel block
Class 1a has a prolonged
repolarization
Two conditions are required for re-entry:
(1) have unidirectional conduction block in any kind of functional circuit
(2) the conduction time around the circuit > refractory period
Re-entry could be terminated by:
(1) converting uni- to bi-directional block
(2) or by prolonging refractory time
Prolonged refractoriness can suppress re-entrant arrhythmias because:
- refractory tissue will not generate an action potential
* and so the re-entrant wave of excitation is extinguished
Class II drugs (β-adrenergic receptor blockers) CURRENT
↓ If current
↓ L-type Ca2+ current
↓ K+ current
β-blockers are consequently used to terminate arrhythmias that involve AV
nodal re-entry, and in controlling ventricular rate during _______
atrial fibrillation.
Class II drugs (β-adrenergic receptor blockers) RESULTS
↓ rate of diastolic depolarization in pacing cells
↓ upstroke rate, and slows repolarization, particularly in AV nodal myocytes
Adenosine-induced changes in membrane currents:
↓ SA node and AV node firing rate
↓ conduction rate in the AV node