Antiarrhythmai drugs Flashcards
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
- must be a block
- block must be unidirectional (allows conduction from other side)
- 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)
whereas
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?
NO
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
Flecainide pharmacokinetics
Well absorbed, half-life 20 hrs, elimination: liver and kidney
Flecainide adverse effects
Increases mortality in patients with ventricular tachyarrhythmias, myocardial infarction and ventricular ectopy
Propafenone MOA
Potent blocker of Na+ channels with slow kinetics, may also block K+ channels
Structural similarity to propranolol with weak β-blocking activity
Propafenone Indications
Supraventricular arrhythmias in patients with otherwise normal hearts
Propafenone adverse effects/toxicity
Probably same as flecainide (arrhythmogenic)
Sinus bradycardia/bronchospasm (β-blockade)
Metallic taste and constipation
β-adrenoceptor blockers MOA
inhibit normal sympathetic effects that act through
β-adrenoceptors
non-selective blockers
block β1and β2 receptors
Typical drug: Propranolol (other: Sotalol, Timolol)
cardioselective B-blockers
relatively selective β1 blockers
Typical drug: Esmolol (other: Acebutolol)
actions of B-Blockers
inhibit sympathetic influences on cardiac electrical activity
reduce heart rate
decrease intracellular Ca++ overload
decrease pacemaker currents (SA node automaticity)
reduce conduction velocity
decrease catecholamine induced DAD and EAD mediated arrhythmias
indications for B-Blockers
Prevention of recurrent infarction and sudden death
after myocardial infarction
Exercise-induced arrhythmias
Also used for atrial fibrillation, atrial flutter and AV nodal reentry
adverse affects/toxicity of B-blockers
Bradycardia, reduced exercise capacity, heart failure, hypotension, AV block - contraindicated in patients with sinus bradycardia and partial AV block
Bronchospasm, contraindicated in patients with asthma or chronic obstructive pulmonary disease.
Blocking β2-adrenoceptors lowers plasma glucose and β1-blockers lower heart rate - thus tachycardia associated with hypoglycemia in diabetic patients may be masked
Adenosine MOA
- Endogenous purine nucleoside
- Acts via purinergic receptors (GPCR), increases K+ conductance (hyperpolarization) and inhibits cAMP-mediated Ca++ currents
- Primarily acts on atrial tissues (actions similar to acetylcholine only via different receptors)
- Slows AV node conduction and increases AV node refractoriness
- Produces transient cardiac arrest
Adenosine indications
Drug of choice for conversion of paroxysmal supraventricular tachycardia to sinus rhythm !!
Adenosine adverse effects/toxicity
Flushing and shortness of breath, sinus bradycardia, sinus pauses, AV block, decrease in blood pressure
Adenosine pharmacokinetics
Half-life of seconds, rapid i.v. bolus dose required (initially 6 mg i.v.)
Less effective with theophylline/caffein, potentiated by dipyridamole
Vagal maneuvers
- carotid sinus message, diving reflex (cold water on face), Valsalva maneuver.
- slows conduction through AV node. Acute treatment for paroxysmal supraventricular tachycardia (PSVT)
Radiofrequency ablation / Cryoablation
- interrupts reentrant / accessory pathway
- used more frequently to replace anti-arrhythmic drug therapies
Electrical cardioversion can be used for what rhythms
- atrial fibrillation
- ventricular tachycardia and fibrillation
Implantable Cardioverter-Defibrillator (ICD) is used for what rhythm
ventricular fibrillation
what drugs should be used for Conversion to sinus rhythm
Adenosine / Amiodarone
Flecainide
what drugs should be used for Maintenance of sinus rhythm
Amiodarone / Dronedarone
Flecainide / Propafenone
what drugs should be used for Ventricular rate control:
Diltiazem/Verapamil
Propranolol/Esmolol
what drugs should be used for ventricular tachycardia in pts without heart disease
Amiodarone
Lidocaine
what should be done for Ventricular fibrillation
Defibrillation
w/wo Amiodarone
or Lidocaine
what should be done for Atrial fibrillation
Diltiazem/Verapamil
Propranolol
what should be done for Paroxysmal supraventricular tachycardia
Adenosine/Amiodarone
Verapamil/Diltiazem/
Propranolol
