Anda di halaman 1dari 25


A N Mahendra

Department of Pharmacology & Therapy

Faculty of Medicine, Udayana University
Practical aspects…
Normal HR= 60-100 bpm
 VT: large QRS waves in ECG, no P waves,
regular tachycardia
 SVT: small QRS waves in ECG, no P waves,
regular tachycardia
 Polymorphic VT: “birthday party ribbon”
pattern  torsade de pointes
 Supraventricular arrhythmias: atrial flutter,
atrial fibrillation(AF), & SVT
Class 1
 Basic PD: Na channel (INa) blockade
 Action potential duration (APD) modulators

Subclass Action on APD Dissociation

1A Prolongation Dissociate from
channel with
intermediate kinetics
1B Shortening (some Dissociate from
cardiac tissues) channel with rapid
1C Minimal Dissociate from
channel with slow

 Dromotropic & chronotropic-negative,
dissociates from INa with intermediate
kinetics, direct SA & AV nodes-depressants
 Clinical uses: Most atrial & ventricular
arrhythmias; second choice for most
sustained ventricular as. associated with AMI

 PO, IV, IM
 M: hepatic (Procainamide  NAPA)
 E: hepatic, renal
 Adverse effects: hypotension, reversible
lupus-related sx (long-term tx).
 NAPA: associated with torsades de pointes in
patients with renal failure
1A Miscellaneous Agents

 Quinidine: rarely used in arrhythmias; similar

to procainamide, but more toxic (cinchonism,
 Disopyramide: rarely used; similar to
procainamide, but with significant
antimuscarinic effects; may precipitate heart

 Blockade of activated & activated fast
kinetics-channels; does not prolong APD
 Clinical uses:
 VT termination
 Prevention of VF after cardioversion

 IV
 E: hepatic (First-pass metabolism)
 HF & liver ds  dose reduction
 Toxicity: Neurologic sx.
 Lidocaine congener (PO)
 Clinical uses: ventricular arrhythmias &
chronic pain syndromes

 Dissociates from slow-kinetics channels; does
not change APD
 Clinical uses:
 Supraventricular arrhythmias (in normal cardiac
 Do NOT use in post-MI (ischemic conditions)

 PO
 M: hepatic & renal
 Long t1/2 (20 hrs)
 Miscellaneous agents
 Propafenone: PO, hepatic metabolism, weak
beta-blocking activity; SV arrhythmias
 Moricizine: withdrawn (proarrhythmic)
Class 2
 Basic PD: Anti-adrenergic activity (β)
 Direct membrane effects & prolongs APD;
slows SA node automaticity; negative
dromotropic effect on AV node
 Clinical uses:
 Atrial arrhythmias
 Prevention of:
 Recurrent infection
 Sudden death
Class 2

 PO, parenteral
 Toxicity: asthma, AV blockade, acute HF
 Interactions: cardiac depressants &
hypotensive agents
 Miscellaneous drug:
 Esmolol: IV, short-acting; used for intraoperative
& other acute arrhythmias
Class 3
 Basic PD: K channel (IKr) blockade
 APD modulators
 Examples:
 Amiodarone
 Dofetilide
 Sotalol
 Ibutilide
 Dronedarone
 Vernakalant
 INa, IKr, ICa-L channels & beta-adrenoceptors
 APD & QT prolongation
 Negative chronotropic & dromotropic effect
 Low incidence of torsade de pointes
 Clinical uses: serious supraventricular &
ventricular arrhythmias
 PO, IV
 Variable absorption & tissue accumulation;
hepatic metabolism, slow & complex
 Toxicity: bradycardia & heart block in
diseased heart heart, peripheral vasodilation,
pulmonary, thyroid, & hepatic toxicity
 IKr blockade
 APD prolongation, effective refractory period
 Clinical uses: Maintenance or restoration of
sinus rhythm in AF
 PO; renal excretion
 Toxicity: Torsade de pointes (initiate in
 Additive with other QT-prolonging agents
 Sotalol: beta-blocker, prolongs APD; for
ventricular a. & AF
 Ibutilide: K-channel blocker, may activate
inward current,; IV use for conversion in atrial
flutter & AF
 Dronedarone: investigational
 Vernakalant: investigational
Class 4

 Basic PD: Ca2+ channel blockade

 Slows conduction in SA & AV nodes (areas
with Ca2+ -dependent action potential
 Examples:
 Verapamil
 Diltiazem (equivalent to Verapamil)
 ICa-L channels blockade
 Slows SA node automaticity & negative
dromotropic effect
 Negative inotropic effect
 Hypotensive action
 Clinical use: SVTs
 PO, IV
 M: hepatic  caution in hepatic dysfunction.

 Adenosine, Magnesium, & Potassium

 Activates IKr, blocks ICa
 Effect: very brief, usually complete AV
 Clinical use: Paroxysmal SVTs
 IV; Toxicity: flushing, chest tightness,
dizziness; minimal interactions
 PD: unknown exact mechanism; interacts
with sodium, potassium, ATPase, potassium
& calcium channels
 Effects: normalizes/increases plasma Mg
 Clinical uses: torsade de pointes & digitalis-
induced arrhythmias
 IV, dose-dependent duration
 Toxicity: muscle weakness
 Potassium
 Increases potassium permeability & currents
 Effects: Slows ectopic pacemakers, negative
dromotropic effect
 Clinical uses: digitalis-induced arrhythmias &
hypokalemia-associated arrhythmias
 PO, IV
 Toxicity: reentrant arrhythmias, fibrillation or
arrest in overdose
Principles of Antiarrhythmic
 Deciding on appropriate tx depends on
distinguishing supraventricular & ventricular
rhythms  seek expert advice if there is any
 Close monitoring is essential. All
antiarrhythmics have potentially serious side
effects (they may worsen arrhythmias in
certain conditions, such as hyperkalemia)
 Negative inotropic effects tend to be additive
when > 1 drug is needed.
Thank You