Antiarrhythmic Drugs Flashcards
arrhythmia
- Abnormalities of cardiac impulse formation and/or conduction
- Rhythm is NOT normal sinus
- Pharmacologic therapies
- Nonpharmacologic therapies
Intracardiac devices
Ablation Cardioversion
•Arrhythmias are disorders of cardiac impulse formation and /or conduction that result in a rhythm that is not normal sinus rhythm. The resulting heart rates may be outside of the normal of 50 to 100 beats per minute.
the goal of antiarrhythmic drugs
- The goal of antiarrhythmic therapy may be to restore normal cardiac function or alleviate symptoms or prevent sudden cardiac death Unfortunately, antiarrhythmic drugs may not only help control arrhythmias but also can cause them, even during long-term therapy
- Available antiarrhythmic drugs suppress arrhythmias by blocking flow through specific ion channels or by altering autonomic function.
- RESTORE NORMAL HT FUNCTION
- ELIMINATE SYMPTOMS
- PREVENT SUDDEN DEATH &HEMODYNAMIC COLLAPSE
- REDUCE OTHER RISKS ASSOCIATED WITH ARRHYTHMIA (stroke in atrial fibrillation)
- The drugs work because they act specific ion channels or alter autonomic function
mechanisms of arrhythmia
- Enhanced automaticity
- Triggered automaticity
Early – slow heart rate, hypokalemia
Delayed – Ca²⁺ excess
• Reentry Anatomically defined
– a bypass tract Functionally defined
– electrical problem
reentry
The prototypical example of reentry is the WPW syndrome in which patients have an accessory connection between the atrium and ventricle. With each sinus node depolarization, impulses can excite the ventricle via the normal structures (AV node) or the accessory pathway, and this often results in an unusual and characteristic QRS complex in normal sinus rhythm. Importantly, the electrophysiological properties of the AV node and accessory pathways are different:
Accessory pathways usually consist of nonnodal tissue with longer refractory periods and without decremental conduction. Thus, with a premature atrial beat (e.g., from abnormal automaticity), conduction may fail in the accessory pathway but continue, albeit slowly, in the AV node and then through the His-Purkinje system; there the propagating impulse may encounter the ventricular end of the accessory pathway when it is no longer refractory. The likelihood that the accessory pathway is no longer refractory increases as AV nodal conduction slows, demonstrating how slow conduction enables reentry. When the impulse reenters the atrium, it then can reenter the ventricle via the AV node, reenter the atrium via the accessory pathway, and so on
- Reentry is the electrophysiological mechanism responsible for most of the clinically important arrhythmias: Atrial fibrillation Atrial flutter AVNRT AV reentry with a bypass tract VT after MI VF Reentry occurs when a propagating impulse fails to die out after normal activation of the heart and persists to reexcite the heart after the refractory period has ended.
- Impulses propagate by >1 path between 2 points
- The pathways may be:
Anatomically defined - a bypass tract
Functionally defined - cell-cell EP differences
amiodarone
- block K+ channels, also blocks Na+ and Ca++ channels and beta adrenergic receptors
- atrial and ventricular arrhythmias
- side effects: QT prolongation, pulmonary fibrosis, hypo and hyper thyroidism, blue grey skin changes (blue man syndrome), liver toxicity, corneal deposits, increased liver density on CT scan
Class III Mechanism – Unknown
A thyroid hormone analog
Ion channel block – Na+, K+ & Ca2+
Alpha & beta adrenergic receptor block(noncompetitive)
CYP3A4, 2C19 & P-gp disposition
An inactivated state blocker
Electrophysiology
Action potential duration Prolonged
Refractory period Prolonged
Conduction velocity Slowed
PR, QRS & QT intervals Prolonged
USES - A drug with life threatening side effects for life threatening arrhythmias Refractory ventricular arrhythmia termination: VT or VF Atrial fibrillation used when there is structural heart disease Not FDAapproved
•side effects:
Cutaneous Eye- corneal deposits optic neuritis
Lung - fibrosis
Cardiac - VT,VF
Liver - hepatitis
Thyroid - hypo & hyper
AMIODARONE DRUG INTERACTIONS
Pharmacokinetic
Warfarin- inhibits P-450
Digoxin- P-gp inhibition
Pharmacodynamic
Catecholamines
Diltiazem
Propranolol
Ledipasivir/sofosbuvir (Harvoni®) Sx- bradycardia
atrial fibrillation
metorprolol
Beta Adrenergic Blockers
-CLASS II
EP Actions relevant to atrial fibrillation
Automaticity in SA and AV Node
– Decreased AV Nodal Conduction
– Slowed AV Nodal Refractory Period
- Prolonged Net effect: cardiac slowing
•also for hypertension, ischemic heart disease, heart failure
BETA BLOCKERS for ARRHYTHMIAS
Atrial arrhythmias to control ventricular rate
Atrial fibrillation with RVR
Atrial flutter Paroxysmal supraventricular tachycardias
Post- myocardial infarction & HFrEF
Improved survival
•side effects:
CNS Cardiovascular Bad dreams
Aggravation of severe CHF
Depression
Aggravation of occlusive arterial disease
Slow A-V conduction
Pulmonary Bronchospasm in severe asthmatics
Drug interactions
Drugs that impair A-V conduction (digoxin and some calcium channel blockers ( V & D)
verapamil
diltiazem
•Ca++ channel blockers
Calcium channel blockers:
EP Actions relevant to atrial fibrillation
AV Nodal Conduction
– Slowed AV Nodal Refractory Period - Prolonged
Net effect: cardiac slowing
Class IV – Calcium Channel Blocking
•also for ischemic heart disease, hypertension
EP Actions relevant to atrial fibrillation
Activated and inactivated calcium channels blocked
- Rapidly firing tissues
- Incompletely polarized tissues at rest
- Tissues depending only on calcium channels
AV Nodal conduction is slowed and refractory period is prolonged
Net effect is cardiac slowing
Therapeutic Use
Supraventricular tachycardia- to slow ventricular rate
Atrial fibrillation – to slow ventricular rate
•side effcets:
Common (< 10%)
Mild hypotension
Nausea, vomiting
Dizziness
Constipation
Non - cardiogenic edema
Toxicity CARDIAC
- Negative inotropic
- AV block (Digoxin and beta-blockers)
- Hypotension
Drug Interactions - Digoxin plasma levels – Increased (V)
adenosine
- adenosine receptor agonist
- produces transient AV block- diagnosis of arrhythmias
- bronchospasm
- A DIAGNOSTIC AND THERAPEUTIC DRUG FOR THE INITIAL ASSESSMENT and TREATMMENT of reentrant SVTs
Action – Adenosine receptor A1 agonist KACh activated in sinus & AV nodes
- Potassium conductance – increased -
Inhibition c-AMP induced calcium influx
EP Actions
- AV node refractoriness – increased
- AV nodal refractory period – increased
Net effect: slowing, asystole sometimes
Toxicity - Flushing-broncoconstriction
lidocaine
•Na+ channel blocker
digoxin
- inhibits na+/K+ ATPase, positivev ionotropic effect, slows AV conduction by vagal effect
- atrial fibrillation, heart failure
- side effects: arrhythmias, nausea/vomiting, confusion, blurred vision, yellow vision, hyperkalemia
