ANTIARRYTHMIC DRUGS

TACHYCARDIAS
Dr Kirsten Cohen
 Normal Sinus Rhythm
• Heart rhythm is
determined by SA node
= Cardiac Pacemaker
• Called sinus rhythm
• Specialised pacemaker
cells spontaneously
generate APs
• APs spread through the
conducting pathways
• Normal sinus rate 60-
100 beats/min
 Conducting System
• SAN AP triggers atrial
depolarisation
• AVN - Only pathway for
AP to enter ventricles
• Conducts slowly: Complete
atrial systole before
ventricular systole
• Conducts rapidly through
His Bundles & Purkinje –
Ventricular depolarization
& contraction
 Conducting System
• Permits rapid organized
depolarization of
ventricular myocytes
• Necessary for the
efficient generation of
pressure during systole
• Atrial activation complete
0.09s after SAN firing
• Delay at AVN
• Septum activated 0.16s
• Whole ventricle activated
by 0.23s
 Cardiac Action Potential
• Phase 4: RMP
• AP depolarizes cells to
threshold -70mV
• Phase 0:
Rapid depolarization
• Caused by a transient
opening of fast Na
channels
• Increases inward
directed depolarizing
Na+ currents
• Generate "fast-
response" APs
 Cardiac Action Potential
• Phase 1: Initial
repolarization
• Open K channel: transient
outward hyperpolarizing K+
current
• Large increase in slow
inward gCa++ occurs at the
same time
• L-type CaCh open -40mV 
• Repolarization delayed
• Phase 2: Plateau phase
• Plateau phase prolongs AP
duration vs APs in nerves
and skeletal muscle
 Cardiac Action Potential
• Phase 3: Repolarization
• K channels open
• Inactivation of Ca++
channels
• Action potential in non-
pacemaker cells is
primarily determined by
relative changes in fast
Na+, slow Ca++ and K+
conductances and
currents
 Refractory Periods
• Once an AP is initiated,
there is a period (phase
0,1,2, part 3) that a new AP
cannot be initiated.
• Effective or Absolute
refractory period (ERP or
ARP)
• Stimulation of cell by
adjacent cell depolarizing
does not produce new
propagated APs
• Prevents compounded APs
from occurring & limits
frequency of depolarization
and HR
 SAN Pacemaker Potential
• Fully repolarized -60mv
• No stable RMP
• Phase 4: Spontaneous
depolarization or
pacemaker potential
• Slow, inward Na+ channels
open - "funny" currents
• Cause the membrane
potential to begin to
spontaneously depolarize
• During Ph4 there is also a
slow decline in the outward
movement of K+
 SAN Pacemaker Potential
• -50mV T-type CaCh open
• Ca in: further depolarizes
• -40 mV L-type CaCh open
• More Ca in: further depol
• AP threshold -35mV
• Phase 0: Depolarization
• Primarily caused by Ca++
conductance through the
L-type Ca++ channels
• Movement of Ca++ through
these is slow so the rate of
depolarization (Phase 0
slope) is slower than in
other cardiac cells
 SAN Pacemaker Potential
• Phase 3:
Repolarization
• K+ channels open
• Increase the outward
hyperpolarizing K+
currents
• At the same time the L-
type Ca++ channels close
• gCa++ decreases
• Inward depolarizing Ca+
+ currents diminish
• Repolarization
 Regulation of Cardiac APs
• SNS - Increased with
concurrent inhibition vagal tone: 
• NA binds to B1 Rec
• Increases cAMP
• Increases Ca and Na in
• Decreases K out
• Increases slope phase 0
• Non-Nodal tissue:
• More rapid depolarisation
• More forceful contraction
• Pacemaker current (If) enhanced 
• Increase slope phase 4
• Pacemaker potential more rapidly
reaches threshold
• Rate increased
 Regulation of Cardiac APs
• PSNS (Vagal N)
• Ach binds M2 rec
• Increases gK+
• Decreases inward Ca & Na
• Non-Nodal tissue:
• More rapid depolarisation
• More forceful contraction
• Pacemaker current (If)
suppressed
• Decreases pacemaker rate
• Decrease slope of Phase 4
• Hyperpolarizes in Phase 4
• Longer time to reach threshold
voltage
 What is an Arrhythmia ?

• Irregular rhythm
• Abnormal Rate
• Conduction abnormality
 What causes an arrhythmia?
• Changes in automaticity of the PM
• Ectopic foci causing abnormal APs
• Reentry tachycardias
• Block of conduction pathways
• Abnormal conduction pathways (WPW)
• Electrolyte disturbances and DRUGS
• Hypoxic/Ischaemic tissue can undergo
spontaneous depolarisation and become an
ectopic pacemaker
 Re-Entry Mechanism
• Branch 2 has a unidirectional block
• Impulses can travel retrograde (3 to 2)
but not orthograde. 
• An AP will travel down the branch 1, into
the common distal path (br 3), then travel
retrograde through the unidirectional
block in branch 2.
• When the AP exits the block, if it finds
the tissue excitable, it will continue by
traveling down (reenter) the branch 1.
• If it finds the tissue unexcitable (ERP)
the AP will die.
• Tming is critical –AP exiting the block
must find excitable tissue to propagate.
• If it can re-excite the tissue, a circular
pathway of high frequency impulses
(tachyarrhythmia) will become the source
of APs that spread throughout a region of
the heart (ventricle) or the entire heart.
 Rationale for Antiarrhythmic
Drugs
• Restore normal rhythm, rate and conduction
or prevent more dangerous arrhythmias
1. Alter conduction velocity (SAN or AVN)
Alter slope 0 depolarisation or refractoriness
2. Alter excitability of cardiac cells by changing
duration of ERP (usually via changing APD)
ERPinc – Interrupts tachy caused by reentry
APDinc – Can precipitate torsades
3. Suppress abnormal automaticity
 Vaughan-Williams Classification
Class Mechanism Example

I Na channel blockers Lignocaine

Membrane Stabilisers
II Beta Blockers Metoprolol

III K channel blockers Amiodarone

IV Ca channel blockers Verapamil

Other Digoxin. Adenosine.

MgSO4. Atropine
 Class I A Agents
• Block open ACTIVATED Na channels
• Slow phase 0 depolarisation - upstroke of AP
• Lengthen APD and ERP.
• Prolong QRS duration on ECG
• Anticholinergic S/E. Also blocks K Ch.
• Greater affinity for rapidly firing channels
• Disopyramide: Prevent rec VT. - Inotrope
• Quinidine: SVT and VT. Torsades
• Procainamide
 Class I B Agents
• Block INACTIVATED Na channels
• Slow phase 0 depolarisation- Slows upstroke
of AP
• Shorten APD and ERP
• Ratio ERP/APD is increased
• Greater affinity for ischaemic tissue that has
more inactivated channels, little effect on
normal cells – dissociates quickly (0.5sec)
• Lignocaine: VT in heart with normal EF
• Phenytoin
 LIGNOCAINE
• - Cardiac arrest: 1-1.5 mg/kg
to max 3mg/kg
• - Stable wide complex
tachycardia: Start lower 0.5
• Especially in presence of
ischaemia
• Not if poor cardiac function
(Poor EF)
• Watch for signs of toxicity
• New algorithm only in cardiac
arrest
• Infusion within 10 min of
effect - 1-4 mg/min
 Class I C Agents
• Block Na channels.
• Most potent Na channel block
• Dissociate very slowly (10-20 sec)
• Strongly depress conduction in myocardium
• Slow phase 0 depolarisation - upstroke of AP
• No effect on APD
• No effect on QRS
• Flecainide: Prophylaxis in paroxysmal AF
• Propafenone
 Class II Agents
• Beta Blockers - Block B1 receptors in the
heart
• Decrease Sympathetic activity
• Non-Nodal Tissue:
• Increase APD and ERP
• SA and AVN:
• Decrease SR
• Decrease conduction velocity (Block re-entry)
• Inhibit aberrant PM activity
 ATENOLOL
• Non-selective B-Blocker (B1 and B2)
• Indications: Convert or Slow rate in SVTs
• 2nd line after Adenosine/Digoxin/Diltiazem
• IV atenolol 5 mg over 5 minutes
• Repeat to maximum 15 mg.
• 50 mg PO BID if IV works
• Contraindiactions:
• Asthma
• CCF. Poor EF. High degree heart block.
• Ca channel blockers. Cocaine use.
 Class III Agents
• Anti-Fibrillatory agents.
• Block K channels
• Prolong repolarisation
• Prolong APD and ERP
• Useful in Re-Entry tachycardias
• AMIODARONE (also Class IA, II BB)
• SOTALOL (also Class II BB)
 AMIODARONE
• Most tachyarrhythmias
• OK if impaired LV function
• Rate control and converts rhythm
• Cardiac arrest: 300 mg IV push (max 2.2g/24hrs)
• Stable VT: 150 mg IV repeat 10 min or infusion 360
mg IV over 6 hrs (1mg/min)
• Maintenance infusion: 540 mg over 18 hrs (0.5mg/min)
• Side Effects:
• Hypotension. Negative Inotropy. Prolonged QT.
• Photosensitivity. Thyroid disorders.
• Pulmonary alveolitis. Neuropathy.
 Class IV Agents
• Calcium Channel Blockers
• Bind to L-type Ca channels
• Vascular SmM, Cardiac nodal & non-nodal cells
• Decrease firing rate of aberrant PM sites
• Decrease conduction velocity
• Prolong repolarisation
• Especially active at the AVN
• VERAPAMIL
• DILTIAZEM
 VERAPAMIL
• Narrow complex tachycardias
• Terminates PSVT/SVT
• Rate control in AFib/Aflutter
• NOT WPW or VT or high degree block
• NOT with BBlockers
• Negative Inotropy
• Vasodilation – Hypotension
• Dose: 5mg IV bolus. Rpt 15 min max 30 mg
• Diltiazem less adverse effects
 What does Adenosine Do?
• Purine nucleoside
• Acts on A1 adenosine receptors
• Opens Ach sensitive K channels
• Inhibits Ca in current – Suppresses Ca
dependent AP (Nodal)
• Increases K out current – Hyperpolarisation
• Inhibits AVN > SAN
• Increases AVN refractory period
 ADENOSINE
• Interrupts re-entry and aberrant pathways through
AVN – Diagnosis and Treament
• Drug for narrow complex PSVT
• SVT reliant on AV node pathway
• NOT atrial flutter or fibrillation or VT
• Contraindications:
• VT – Hypotension and deterioration
• High degree AV block
• Poison or drug induced tachycardia
• Bronchospasm but short DOA
 ADENOSINE
• Carotid massage and vagal maneuvers first
• Rapid IV push 6mg – 12 mg – 12 mg
• Flush with 20ml N/S
• Record rhythm strip
• FLUSHING
• CHEST PAIN
• ASYSTOLE/BRADY
• VENTRICULAR ECTOPY
 What does Digoxin Do?
• Cardiac glycoside
• Blocks Na/K ATPase pump in heart
• Less ECF Na for Na/Ca pump
• Increased IC Ca
• Inotropic: Increases force of contraction
• AVN increased refractoriness
• Decreases conduction through AVN and SAN
• Negative chronotrope: Slows HR
Reduces ventricular response to SVTs
 DIGOXIN
• Contraindications: WPW. SSS.
• Elderly or renal failure – reduce dose or TOXICITY
• 0.25 to 0.5 mg IV; then 0.25 mg IV every 4 to 6
hours to maximum of 1 mg
• 0.125 to 0.25 mg per day IV or orally
 Take-Home Message
• Anti-arrhythmics are also pro-
arrhythmics
• Dangerous side effects
• If patient is unstable rather cardiovert
• Enlist expert help
• Stick to drugs you know
• Limited choice in SA anyway