mbbs antiarrhythmics 2014 class i [basics]
TRANSCRIPT
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Myocardial cells are excitable!
[Impulse generation, conduction & contraction]
SA Node Impulse generation [Pace maker]
Atria Conduction, contraction
AV Node Conduction
HIS
purkinjesystem
Conduction
Ventricles Conduction, contraction2
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Rhythmic
Electrical and mechanical activity
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Arrhythmias
What is normal cardiac rhythm?
What is rhythm?
Any activity in the universeoccurring again and again at regularintervals
Arrhythmia-abnormal rhythm
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Normal cardiac rhythm
Impulse generation
Impulse propagation
Sinus
tachycardia
Atrial rhythm
WPW
syndrome
First degree
HB
Normal velocity
Rate-60-100 BPM
Pace maker-Sinus
Normal conduction pathways
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Types of arrhythmias
Bradyarrhythmias
Tachyarrhythmias
Supraventricular Atrial fibrillation [AF]
Atrial flutter [AFL]
Paroxysmal supraventricular
tachycardia [PSVT]
Ventricular Ventricular fibrillation & Flutter [VF,
VFL]
Ventricular tachycardia [VT]
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Activities in the heart
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Mechanical activity[contraction & CO]
Electrical activity [Imp.gen&cond.]
Action potentials
Depolarization
Repolarization
Ionic fluxes
Arrhythmias Anti arrhythmics
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K K
K
RP
-90
TP
-70
Symp
Para
Symp
4
01
2
3
K
K K
4
0 3
4
Nodal tissue Myocyte
TP
-40
RP
-60
++++
Cardiac action potential 21
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AP in non-pacemaker tissue
AP in pacemaker tissue
Ca NaKK
4
4
0
3
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Pathogenesis of arrhythmias
Abnormalities of impulse
generation
Abnormalities of spontaneous
automaticity
Abnormalities of triggered
automaticity
Abnormalities of impulse
propagation
Impulse block
Re-entry phenomenon
Anatomically defined Functionally defined18
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Triggered automaticity[Abnormality of impulse generation] Re-entry phenomenon
[Circus movement][Abnormality of impulse conduction]
Pathogenesis of arrhythmia[Mechanisms of arrhythmias]
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Pathogenesis of arrhythmiasAbnormalities of impulse
generation
Spontaneous automaticityAbnormalities of triggered
automaticity[ After depolarization]
Atrial and ventricular tachycardia
Not commonAcutely ill pts.
Underlying disease+
Treat the cause
Early after depolarization[EADs]
Delayed after depolarization[DADs]
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Pathogenesis of arrhythmias
Abnormalities of triggered
automaticity
Early after depolarization[EADs]
4
0
1, 2, 3
4
RMP
TP
E
A
D
K+ channels are defective-slow
[QT prolongation]-Torse-De-Pontes
Drugs[K+ channel blockers]
Hypokalemia
Low HR
[Tt increase HR]
If Phase 4 [repolarization] is prolonged voltage gated [Na or Ca] channels
may be activated prematurely to produce EADs 14
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Pathogenesis of arrhythmiasAbnormalities of triggered
automaticity
Delayed after depolarization [DADs]
4
0
1, 2,
3
4
RMP
TP
D
A
D
Fluctuations in baseline-due to Ca++ loading
-If baseline comes near TP -DAD may occur
Adrenergic stressDigitalis toxicity
Ischemia
E
A
D
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Pathogenesis of arrhythmiasAbnormalities of impulse
propagation
Impulse block[Heart blocks]
AV blocksBeta blockers
Calcium channel
blockers
Digitalis toxicityAdenosine
Ischemia
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Re-entry
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Re-entry
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Pathogenesis of arrhythmiasRe-entry phenomenon
Anatomically defined Functionally defined
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AVAVN
SAN
1. 2 pathways
2. Nearly parallel
3. Connected proximally and distally
4. Different velocities & RP
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1. Two roughly parallel conductingpathways must be present &
2. Connected proximally and distallyby conducting tissue, forming apotential electrical circuit
3. One pathway must have a longerrefractory period
4. Pathway with the shorterrefractory period must conduct
electrical impulses more slowly thandoes the opposite pathway
Re-entry phenomenon
Initiation of reentry
An appropriately timed, prematureelectrical impulse can be blocked inpathway B (which has a relatively longrefractory period)
While conducting down pathway A.
Because conduction down pathway A isslow, pathway B has time to recover,allowing the impulse to conductretrogradely up pathway B.
The impulse can then reenter pathwayA.
A continuously circulating impulse is thus
established. 9
B BA
A
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Types of arrhythmias
Bradyarrhythmias
Tachyarrhythmias
Supraventricular Atrial fibrillation [AF]
Atrial flutter [AFL]
Paroxysmal supraventricular
tachycardia [PSVT]
Ventricular Ventricular fibrillation & Flutter [VF,
VFL]
Ventricular tachycardia [VT]
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How do antiarrhythmics work?
Tachyarrhythmias mediated by changes inthe cardiac action potential
Drugs that alter the action potential altercardiac arrhythmias [By altering ionicfluxes]
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How do antiarrhythmics work?
Effect AP
Change the shape of the cardiac AP.
1. Conduction velocity [CV].
2. Refractory period [RP]
3. Automaticity [AM]
Antiarrhythmic drugs do this by altering the
channels that control the flow of ions across
the cardiac cell membrane.
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Antiarrhythmics
Classification [Singh-Vaughan-Williams]Sodium-channel-
blockers
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Beta-blockersPot.channel
blockers
Calcium channel
blockers
Conduction Velocity
Refractory Period
Automaticity
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How do antiarrhythmics work?
Effect on AP
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Increase RP[APD]
Decrease RP[APD]
1. 2 pathways
2. Nearly parallel
3. Connected proximally and
distally
4. Different velocities & RP
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Antiarrhythmics
Classification [Singh-Vaughn-Williams]Sodium-channel-
blockers
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Beta-blockers
Propranolol
Pot.channel
blockers
Amiodarone
Calcium channel
blockers
Verapamil
Diltiazem
Miscellaneous
Adenosine
Magnesium
Digitalis
Atropine
Procainamide
Sotalol,CV-Moderately
, CV-Mild
, CV-Profound
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Na+ Channel blockers
Class 1A.Eg. Procainamide
.CVRP
.Atria & Ventricles
.Oral & i.v.
PK:Acetylation
Uses:AF, Reentrant
tachy,VT
.ADEs:
Anticholinergic
SLE, agranulocytosis
Proarrhythmic-
Torse-De-Pontes
3
Class 1BEg.Lignocaine
Na+ Channel
No action at low HR
User dependent
APD[RP]Only ventricles
i.v[bolus-infusion]
Use: Vent.arrhythmias
ADEs: CNS
Proarrhythmic-rare
Class 1CEg. Porpafenone
Conduction-V.potent
Oral
Beta blocker, -ve inotropic
Uses: atrial &
Vent.arrhythmias
ADEs: Visual disturbances
GIT effects
Reserve drug
Diisopyramide
[-ve inotropic]
Mexiletine[O] Flecanide
[No beta blockade]
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Class II-BetablockersEg.Propranolol
Mild, blunt arrhythmogenic effect
SA Node-Phase 4 is blunted-reduces automaticity
AV Node-slows conduction
Protective-Prevents reentrant tachycardias Uses:
Effective in arrhythmias where SA & AV nodes are involved
AF & AFL-Reduces ventricular response
Not effective in treating ventricular arrhythmias, but effectivelyprotects.
Yes, last slide!