3. How do antiarrhythmics work?
• Tachyarrhythmias mediated by changes in
the cardiac action potential
• Drugs that alter the action potential alter
cardiac arrhythmias [By altering ionic
fluxes]
31
4. How do antiarrhythmics work?
Effect AP
• Change the shape of the cardiac AP.
Ca or Na
K
B Blocker
1. Conduction velocity [CV].
Ca or Na 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. 32
7. Na+ Channel blockers
Class 1A Class 1B Class 1C
Eg.Lignocaine
.Eg. Procainamide Eg. Porpaafenone
Na+ Channel
.CV↓RP↑ ↓↓↓ Conduction-V.potent
No action at low HR
.Atria & Ventricles Oral
User dependent
.Oral & i.v. -ve inotropic
APD[RP] ↓
PK:Acetylation Uses: atrial &
Only ventricles Vent.arrhythmias
Uses:AF, Reentrant
tachy,VT i.v[bolus-infusion] ADEs: Visual disturbances
.ADEs: Use: Vent.arrhythmias GIT effects
Anticholinergic ADEs: CNS Reserve drug
SLE Proarrhythmic-rare
Proarrhythmic- Torse-De
Pointes
38
8. Na+ Channel blockers
Class 1A Class 1B Class 1C
Procainamide Lignocaine Propafenone
Diisopyramide Mexiletine[O] [Also B-blocker]
Reserve drug
39
9. Class II-Betablockers
Eg.atenolol,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 effectively
protects.
40
10. Class III-K+ channel blockers
Eg.Amiodarone
• K+ channel blocker[CL III], Na channel
blocker[CL I], betablockade[CL II], Ca channel
blockade[CL IV]
• Prolongs APD-ERP
• Large volume of dist.-slow action, loading dose
• Immediate antiarrhythmic effects are due to
non CL III effects
• Oral and i.v. administration
41
11. Class III-K+ channel blockers
Eg.Amiodarone
• Uses:
• Broad spectrum antiarrhythmic
• Most effective in recurrent ventricular fibrillation
• AF, reentrant tachycardias-AV nodal, WPW
syndrome
• Others-Sotalol. Ibutilide, dobutilide
42
12. Class III-K+ channel blockers
Eg.Amiodarone
• ADEs: 15% to 50% of pts.
• Cumulative drug
• GIT-nausea, vomiting,esophageal reflux
• Reversible elevation of liver transaminases
• Pneumonitis, pulmonary fibrosis
• Iodine containing compound-prevents peripheral
conversion of T4 to T3
• Hypothyroidism or hyperthyroidism
• Cutaneous, neurological, ocular symptoms
• ADEs:Torsede-de-pointes[Not common] 43
14. Class IV-Ca++ channel blockers
Verapamil & Diltiazem
• Low BA
• Inhibit Ca ++ dependent depolarization in SA &
AV node
• ↓Automaticity, ↓ conduction and RP
• Uses:
• Control Vent.response in atrial
tachyarrhythmias
• AV nodal and bypass reentrant arrhythmias
45
15. Unclassified antiarrhythmics
• Digoxin-In AF to lower vent.response
• Adenosine-Short acting, depresses AV node,
used in reentrant tachyarrhythmi s
[Adenosine R→K Channels→Hyperpolarization
• Magnesium-Torsades-de-pointes, digitalis
toxicity
• Atropine-H.block
• Isoprenaline-H.block, Torsede de pointes
• Others-Azimilide, Dronedarone, tedisamil,46
16. Principles in clinical use of
antiarrhythmics
• Narrow margin of safety
• Proarrhythmics
• Non-pharmacological measures [pacing,
cardioversion]
47
17. Principle-1
• Identify and remove precipitating factors
1. Electrolyte disturbances
2. Hypoxia
3. Ischemia
4. Digoxin
5. Other drugs used for non cardiac
conditions[Erythromycin, pentamidine,
antipsychotics]
48
18. Principle-2
• Establish goals
1. Some should not be treated
Eg. Asymptomatic ventricular ectopics
2. Symptoms- Sensation of irregular beats,
Syncope, breathlessness, cardiac failure
3. Choosing therapeutic approaches-
• Restoring sinus rhythm-
• Reducing ventricular rate 49
