Antiarrhythmai drugs Flashcards Preview

Pharm block 4 hemostasis and cardiac > Antiarrhythmai drugs > Flashcards

Flashcards in Antiarrhythmai drugs Deck (56)
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what is an EAD and when does it occur

occur at slow heart rates, get an extra depolarization from the plateau of the membrane potential (during repolarization)


what is a DAD and when does it occur

occur at fast HRs, an extra depolarization occurs from the resting potential


what are the requirements for re-entry

1. must be a block
2. block must be unidirectional (allows conduction from other side)
3. theres slow conduction through the block (slower than the depolarization of the cells on the other side allowing them to be reacitivated


what are the goals of anti-arrhythmic therapy

Aimed to reduce ectopic pacemaker activity and/or
modify conduction characteristics to disable re-entry circuits


what are possible anti-arrhythmic mechanisms

Na+ channel blockade

Blockade of sympathetic autonomic effects (β-receptors)

Prolongation of the effective refractory period
 (longer QT interval)
Ca++ channel blockade


Use-dependent or state-dependent drug action

channels that are used frequently or inactivated are more susceptible, e.g. during fast tachycardia (many channel activations/inactivations) or in ischemic or infarcted tissues (more positive resting potential)


channels in normal cells rapidly loose the drug during resting phase

Selective blockade of depolarized cells


why wouldn't you give anti-arrhythmic drugs prophylactically

However, anti-arrhythmic drugs DO NOT ACT SPECIFICALLY and can also depress
conduction in normal cells, leading to drug-induced arrhythmia !!!!


do you treat an asymptomatic or mildly symptomatic arrhythmia?



how are anti-arrhythmic drugs classified

Anti-arrhythmic drugs are classified by their PREDOMINANT effect on the action potential and/or PREDOMINANT cellular mechanism of action.

Many drugs have multiple effects that are related to different classes of drug action.

Metabolites of drugs also may be biological active via different mechanisms of action.


Vaughan Williams Classification of Anti-Arrhythmic Drug Actions Class I :

Class I : Na+ channel blockers


Vaughan Williams Classification of Anti-Arrhythmic Drug Actions Class II

Class II: β-adrenoceptor blockers


Vaughan Williams Classification of Anti-Arrhythmic Drug Actions Class III

Class III: Prolongation of action potential duration


Vaughan Williams Classification of Anti-Arrhythmic Drug Actions Class IV

Class IV: Ca++ channel blockers


what is the main function of class I drugs

Na+ channel blockers, local anesthetic action


what is the MOA of Na+ channel blockers

Block fast Na+ channels (Phase 0 in non-nodal cells, fast response action potential) (these are found in the heart and nerve endings)

Actions (therapeutic actions and side-effects) depend on heart rate, membrane potential and drug specific blocking kinetics


what are the subclasses of Na+ channel blockers

Class 1A: intermediate kinetics, APD increased
Class 1B: fast kinetics, APD decreased
Class 1C: slow kinetics, no effect on APD


what are the drugs in class 1A

Procainamide, Quinidine, Disopyramide


what are the drugs in class 1B

*Lidocaine, Mexiletine


what are the drugs in class 1C

Flecainide, Propafenone


Procainamide and quinidine effects

Slows upstroke of AP, conduction, prolongs QRS complex
Direct depressant actions on SA and AV nodes
More effective in depolarized cells (use/state-dependent action)


Procainamide and quinidine indications

Atrial and ventricular arrhythmias

Drug of second or third choice (after lidocaine and amiodarone) for ventricular arrhythmias after acute myocardial infarction


Procainamide pharmacokinetics

- Administered i.v., i.m., p.o.
- Metabolite N-acetylprocainamide (NAPA) has class 3 activity
- Elimination via liver and kidney (NAPA), 
 dose reduction with renal failure
- half-life: 3-4 hrs.


Procainamide adverse effects/toxicity

• Ganglion blocking properties,
• risk of hypotension
• Anti-cholinergic effects
• Induction of torsade de pointes arrhytmia (NAPA) !!
• Long term: Lupus erythematosus syndrome (arthritis, pleuritis…)
• in 30% of all patients


Quinidine adverse effects

Rarely used because of cardiac and extra-cardiac
adverse effects

Ganglion blocking properties, risk of hypotension
(>> procainamide)

Anti-cholinergic effects, increases sinus rate and AV conduction, may require co-administration of drugs that slow AV conduction

Induction of ventricular fibrillation and torsade de pointes !!

Cinchonism: headache, dizziness, tinnitus


Lidocaine pharmacokinetics

Use/state-dependent drug action
rapid kinetics at normal resting potential: No effect on conduction, recovery from block between action potential

selective depression of conduction in depolarized (ischemic) cells

I.v. only, extensive first-pass hepatic metabolism
half-life 1-2 hrs, > 3-6 hrs with liver diseases


Lidocaine indications

High degree if effectiveness in arrhythmias after myocardial infarction

Drug of 1st choice for treatment of ventricular tachycardia and fibrillation after cardioversion in the setting of ischemia/infarction

But: prophylactic treatment not recommended (may increase mortality


Mexiletine's off label use

Off-label use: chronic pain (diabetic neuropathy, nerve injury)


what is an orally active lidocaine analogue

Mexiletine (actions and side effects the same as lidocaine)


Flecainide MOA

Potent blocker of Na+ and K+ channels with slow kinetics
No anti-cholinergic effects

class 1C


Flecainide indications

Supraventricular arrhythmias in patients with otherwise normal hearts