anti arrhythmic drugs Flashcards
What are class III anti-arrhythmic agents ?
They are potassium channel blockers that inhibit potassium outward current or refflux.
Class I agents work by blocking ____________
Cardiac voltage-operated sodium channels
list four class 2 anti arrhythmic agents?
propranolol (non-selective)
atenolol
metoprolol
bisoprolol (ß1-adrenoceptor (cardio)selective)
The major anti-arrhythmic action of class 1 therapeutic contributions are to interrupt ________
re-entry circuits and reduce automaticity
Class 1 chief related site of action is phase 0 of non-nodal Myocardial cells, what do they do to stop arrhythmias?
they act on Myocardial cells; and in particular, rapid sodium inward current during (phase 0) depolarisation.
with class 1 agents, Sodium entry is inhibited and phase 0 depressed. what is achieved by doing this?
Reduced excitability and slowed impulse conduction (decreased conduction velocity)
Class I agents are further subdivided into class _________
IA, IB and IC
class IA agents exhibit the additional property of _____________ (which leads to an extended action potential arising from a protracted phase 2/delayed phase 3
Potassium channel blockade
List three three class 1 drugs
Flecainide (Class 1C agent)
Lidocaine (Class 1B agent)
Quinidine (Class 1A agent)
List the mechanism of Lidocaine
Mild sodium channel blockade
Associates and dissociates rapidly with sodium channel, prefers open and inactivated states for binding, targets ischaemic tissue with little effect on normal myocardium
List the mechanism of Flecainide
Marked sodium channel blockade
Associates and dissociates slowly with sodium channel, affects normal + damaged myocardium non-selectively
List the mechanism of Quinidine
Moderate sodium channel blockade
Associates and dissociates at intermediate rate with sodium channel
Name three class III anti-arrhythmic agents
amiodarone,
dronedarone
vernakalant
What are the effects of class III anti-arrhythmic agents ?
Delays phase 3 repolarisation (inhibit potassium loss) and extends phase 2 in non-nodal cells.
Increases action potential duration and refractory period
Reduce possibility of re-entry circuits
What are class IV anti-arrhythmic drugs?
calcium entry blockers of the non-dihydropyridine class, which exhibit pronounced activity at voltage-operated, cardiac L-type calcium channels
What are examples of class IV anti-arrhythmic drugs?
verapamil, diltiazem
What are the effects of class IV anti-arrhythmic drugs?
Reduce nodal excitability and a reduced heart rate (negative chronotropy) + firing rate of SAN + conduction rate of AVN
Increase action potential duration + refractory period in nodal cells
Reduce action potential duration + refractory period in non-nodal cells
Provide ventricular rate control in atrial tachycardia and reduce triggered automaticity
what do class II anti arrhythmic agents do
Block catecholamine + cAMP-mediated electrical events in: phase 4 of nodal tissue (slope depressed); phase 2 of non-nodal tissue (extended due to delayed onset of phase 3 + reduced calcium entry)
Increase action potential duration + refractory period
Oppose pro-arrhythmic actions of catecholamines
Prevent sinus tachycardia, abnormal + triggered automaticity
list 4 class II anti arrhythmic agents?
propranolol (non-selective)
atenolol
metoprolol
bisoprolol (ß1-adrenoceptor (cardio)selective)
________-are very simply beta-adrenoceptor antagonists
class II anti arrhythmic agents
list 3 selective or cardio-selective beta1-adrenceptor blockers
atenolol
metoprolol
bisoprolol
list the non-selective beta1-adrenceptor blockers.
propranolol
explain the mechanism for beta-adrenoceptor antagonists or class II anti arrhythmic agents.
hese agents prevent cardiac signalling by the catecholamine beta1-adrenoceptor agonists noradrenaline and adrenaline. Beta-adenoceptor blockade results in a fall in cAMP levels and cAMP-mediated intracellular events. These include events in nodal tissue like the SAN, to enhance the pacemaker current and raise the slope of phase 4 (causing a rise in heart rate or sinus tachycardia) and an associated shortening of phase 2 in non-nodal tissue (owing to an acceleration of phase 3 repolarisation). These 2 events orchestrated by cAMP are complementary, as the rise in heart rate in response to e.g. adrenaline must be accommodated by a reduced action potential duration – there is basically less time for the action potential between heart beats. At the same time as adrenaline-induced tachycardia, e.g. during a general sympathetic discharge or “fight-or-flight” response, there is also an increase in cardiac force of contraction (or positive inotropy). This increase in force may at first sound at odds with the short (non-nodal) phase 2 (i.e. the window for calcium entry needed for calcium-induced calcium release and ultimately for contraction) caused by adrenaline; but the fact is that cAMP also enhances calcium entry through L-type calcium channels in phase 2. This then provides more calcium-induced calcium release (from the sarcoplasmic reticulum) for contraction, in the face of a shorter phase 2. The major anti-arrhythmic outcomes of beta-adrenoceptor blockade are therefore predictably: depressed nodal phase 4 slope and lowered heart rate; and prolonged non-nodal phase 2 owing to a delayed phase 3, which extends action potential duration and refractory period. Hence, class II agents prevent automaticity related to excessive signalling activity by catecholamines (e.g. during ischaemia, myocardial infarction and heart failure) while also reducing heart rate (negative chronotropy). Cardiac beta-adrenoceptor blockade is also typically associated with negative inotropy.
which class II anti arrhythmic agents is cardiac selective
bisoprolol
Class 1 chief related site of action is
phase 0 of non-nodal myocadiac cells
___________prefers open and inactivated states for binding, targets ischaemic tissue with little effect on normal myocardium
lidocaine
_________________Associates and dissociates slowly with sodium channel, affects normal + damaged myocardium non-selectively
Flecainide
_____________Associates and dissociates at intermediate rate with sodium channel
quinidine
