Anti-Arrhythmic Drugs Flashcards
Class IA antiarrhythmics
Quinidine
Procainamide
Disopyramide
Class IA actions and changes on EKG
Na+ channel blockers
Also inhibit K+ channels
Slow rate of change of phase 0 = slowing conduction, prolong AP and increase ventricular refractory period
Prolong phase 3 = prolongs refractory period = increases length of AP
Increases QRS and QT intervals:
Na+ channel block pushes phase 0 to the right and decreases slope of phase 0 = increased QRS
K+ channel block prolongs repolarization = increases QT –> can lead to early after depolarization occurring because some Na+ channels get reactivated ready to be opened again –> can cause further arrhythmias
Class IA clinical applications
Can suppress both supraventricular and ventricular arrhythmias as they affect myocardial AP
Replaced by more effective and safer drugs
Quinidine AE, PK and contraindications
Blocks Na+ and K+ channels (class IA)
AE:
- Pro-arrhythmic: torsades de pointes
- SA or AV block
- Cinchonism: tinnitus, blurred vision, headache, psychosis
- N/V and diarrhea
- Thrombocytopenic purpura
- Toxic doses: ventricular tachycardia (exacerbated by hyperkalemia)
PK:
Oral or IV
Inhibits CYP2D6, CYP3A4 and P-glycoprotein
Contraindications in patients with complete heart block
Use carefully in patient with:
Prolonged QT, history of torsades de pointes, incomplete heart block, HF, myocarditis
Procainamide AE, PK and contraindications
Class IA
PK:
- IV only
- Metabolised by acetylation by CYP2D6 to NAPA which causes the K+ channel block and prolongs duration of AP
AE:
- Reversible lupus-like syndrome
- Toxic doses: systole, induction of ventricular arrhythmias (because it prolongs QT)
- CNS effects: hallucinations, depression, psychosis
- Hypotension
Contraindications: Hypersensitivity - Complete heart block - SLE - 2nd degree AV block - Torsades de pointes
Disopyramide actions and AE
Class IA drug (blocks Na+ and K+ channels) Also has: - Strong negative inotropic effects - Strong antimuscarinic effects - Causes peripheral vasoconstriction
AE:
- Pronounced negative inotropic effects (decreases CO)
- Severe antimuscarinic effects: dry mount, urinary retention, blurred vision, constipation
- May induce hypotension and cardiac failure
Class IB antiarrhythmics, actions and changes on EKG
Lidocaine
Mexiletine
Na+ channel blockers
Slow phase 0 and decrease slope of phase 4
Shortens phase 3 repolarization - shortens length of AP but it is not clinically significant
Rapidly associate and dissociate with Na+ channels –> least affinity for Na+ channels —> If there are normal cells, unlikely to see any changes when these drugs are given –> no changes on EKG as it only effects very fast firing tissues –> more specific for arrhythmic tissues
Increases QRS interval (but less change than class IA) Small decrease in QT interval
Lidocaine MOA, PK and clinical applications
Local anaesthetic
More effect on ischemic or diseased tissue
Little effect on K+ channels
PK:
Given IV only (extensive first pass metabolism)
Wide toxic-therapeutic ratio
Used for:
- Acute treatment of ventricular arrhythmias from MI or cardiac manipulation (eg: cardiac surgery)
- Treatment of digitalis induced arrhythmias (digoxin toxicity)
- Only used to treat ventricular arrhythmias
Lidocaine AE
Wide toxic-therapeutic ratio - hard to overdose
CNS effects - drowsiness, slurred speech
No negative inotropic effect
Cardiac arrhythmias (<10%)
Toxic doses: convulsion and coma
Mexiletine MOA, PK, clinical applications and AE
Orally active derivative of lidocaine
Can be given orally or IV
Used for management of severe ventricular arrhythmias (does not treat atrial arrhythmias)
AE: Mainly CNS and GI effects
Class IC antiarrhytmics actions and changes in EKG
Flecainide
Propafernone
Potent Na+ channel blockers Depression of phase 0 = marked slowing of conduction of AP but little effect on duration or ventricular refractory period Associate and dissociate slowly with Na+ channels --> highest affinity for Na+ channels therefore for have the biggest increase in QRS out of all class I drugs
Increase QRS but no effect on QT interval
Slow prominent effects even at normal heart rates (pro-arrhythmic)
Flecainide clinical applications
Class IC drugs that can correct the arrhythmia, dampen down the extra impulses and allow the dominant impulse from the SA node to control the HR –> can put the patient back into sinus rhythm
Severe symptomatic ventricular arrhythmias, premature ventricular contraction or ventricular tachycardia resistant to other therapies
Severe symptomatic supraventricular arrhythmia and prevention of a. fib
Flecainide AE and contraindications
Negative inotropic effects (aggrevates CHF)
CNS effects: dizziness, blurred vision, headache
GI effects: N/V, diarrhea
Life-Threatening arrhythmias and ventricular tachycardia
Contraindicated in patients with CHF as it is associated with fatal arrhythmias in persons with structural heart disease
Propafernone clinical applications
Treatment of life-threatening symptomatic ventricular arrhythmias
Maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation
Propafernone AE and contraindications
Similar to flecainide:
Negative inotropic effects (aggrevates CHF)
CNS effects: dizziness, blurred vision, headache
GI effects: N/V, diarrhea
Life-Threatening arrhythmias and ventricular tachycardia
Contraindications:
- Heart failure
- Has b-blocking activity: cannot give to patients with bronchospasm (COPD, asthma)
Class II antiarrhythmics, actions and changes on EKG
b-blockers: metoprolol, propanolol and esmolol
- Reduce both heart rate and myocardial contractility (negative inotropy and decreased PVR)
- Will have main effect in SA node and the AV node
- Slow conduction of impulses through myocardial conducting system
- Reduce rate of spontaneous depolarisation in cells with pacemaker activity
Increase PR interval:
- Decreased slope of phase 4 depolarisation (nodal AP)
- Prolong repolarization at AV node
Class II antiarrhythmics clinical applications (3)
1) Reduce incidence of sudden arrhythmic death post MI
2) Control of supra ventricular tachycardias (atrial fibrillation and flutter, AV nodal re-entrant tachycardias) : - This will not cure the arrhythmia as they do not act directly on the atria where the arrhythmia is originating
- Can prevent the atrial arrhythmia from becoming a ventricular arrhythmia
- Will not put it back into sinus rhythm
3) Ventricular tachycardias (catecholamine induced or due to digoxin toxicity)
- If there is a catecholamine excess, then these drugs are a good choice as they will dampen effects in both nodes
Esmolol clinical applications
Short acting b1 selective antagonist = class II drug
t1/2 = 9 minutes
Used IV for treatment of acute arrhythmias occurring during surgery or in emergency situations
Class II antiarrhythmics contraindications
- Patients taking Ca+ channel blockers
- Acute CHF (do not want to drop CO further)
- Severe bradycardia
- 2nd or 3rd degree heart block
- Propanolol: asthma and COPD
Class III antiarrhythmics main actions
Amiodarone
Sotalol
Dofetilide
K+ channel blockers –> prolong phase 3 depolarisation –> prolong AP without altering phase 0 or RMP
Prolong effective refractory period
All have potential to induce arrhythmias (increased risk of after depolarizations which can lead to torsades des pointes)
Amiodarone MOA and effects on EKG
Related structurally to thyroxine (contains iodine)
Complex MOA:
- Has class I, II, III and some IV effects
- Dominant effect = K+ channel blockade
- Blocks mostly inactivated Na+ channels
- Blocks Ca+ channels and b-blocker: decreases AV conduction and sinus node function
- Weak Ca+ channel blocker
- Inhibits adrenergic stimulation
- Anti-anginal activity
Will increase QRS, QT and PR intervals on EKG
Benefit is that the arrhythmias that can be caused by these drugs are the Torsade des pointes (after depolarizations) due to the blockade of the K+ channels (class III activity) —> These can be caused by an increase in Na+ current or even Ca2+ current (digoxin) —> But since this drug is a Na+ and Ca2+ blocker, it will treat its own arrhythmias
**Only drug that extends QT but does not increase risk of ventricular arrhythmias.
Amiodarone clinical applications (3)
1) Used to manage ventricular and supra ventricular arrhythmias
2) DOC for acute ventricular tachycardia refractory to cardioversion shock
3) Low doses for maintaining sinus rhythm in patients with atrial fibrillation (rate and rhythm control)
Amiodarone PK
Oral and IV
Half-life: several weeks, distributes in adipose tissue so a loading dose is needed
Full clinical effects and AE may take 6 weeks to achieve
Amiodarone AE and contraindications
Long term use: > 50% show severe AE (many are dose-related and reversible)
- Interstitial pulmonary fibrosis
- Blue skin discolorizution (iodine accumulation)
- Low incidence of torsades de pointes (even though it increases QT)
- Hyper or hypothyroidism
- Liver toxicity
- Photosensitivity
- Bradycardia
- AV block
Contraindications:
- Patients taking: digoxin, theophylline, warfarin and quinidine (effects other drugs that extensively protein bound)
- Bradycardia
- SA or AV block
- Severe hypotension
- Severe respiratory failure
Sotalol MOA and effects on EKG
Class III drug
- K+ channel blocker and potent non-selective b-blocker
- Inhibits rapid outward K+ current
- Acts on SA/AV node to slow conduction of impulses
- Prolongs repolarizations and duration of AP
- Lengthens refractory period
Increases QT and PR intervals
Sotalol clinical applications, AE and contraindications
Can be used for both ventricular and supraventricualr arrhythmias
- Maintenance of sinus rhythm in patients with atrial fibrillation or flutter
AE:
- Same as b-blockers
- Torsades de pointes (prolongs QT interval)
Contraindications:
- Use with caution in patients with renal impairment
Dofetilide MOA and changes in EKG
Class III drug: potent and pure K+ channel blocker
Increases QT interval only
Converts atrial fibrillation or flutter to normal sinus rhythm
Dofetilide PK and AE
Excreted in urine (80% unchanged)
–> Renal failure can lead to drug accumulation in unchanged, active form which can lead to increased AE
AE:
- Torsades des pointes
- Headache
- Chest pain
- Dizziness
- Ventricular tachycardia
Class IV antiarrhythmics
Diltiazem
Verapamil
Ca+ channel blockers
Decrease inward Ca+ current –> decreased rate of phase 0 depolarisation
Slow conduction in tissues dependant on Ca+ current –> main effects on SA and AV nodes
Bind only to open, depolarised channels, preventing depolarisation before drug dissociates
Slow conduction and prolong effective refractory period
Also inhibit vascular Ca+ channels
Major effects:
- Decreased PVR
- Decreased contractility (negative inotropy)
- Decreased heart rate (negative chronotropy)
- Decreased condition velocity (negative dromotropy)
Increase PR interval (due to slow rate of phase 0)
Class IV antiarrhythmics clinical applications
More effective against atrial arrhythmias
1) Supraventricular tachycardia (but cannot cure arrhythmia)
2) Reduction of ventricular rate in atrial fibrillation and flutter
3) Hypertension (1st line drugs)
4) Diastolic heart failure (cannot be used in systolic)
5) Angina
Class IV antiarrhythmics AE and contraindications
Negative inotropy
CNS effects - headache, fatigue, dizziness
GI effects - constipation (especially with verapamil)
Contraindications:
- Verapamil cause increase concentration of other CVS drugs –> digoxin, dofetilide, simvastatin and lovastatin
- Patients taking b-blockers
- 2nd or 3rd degree heart blocker
- Severe left ventricular dysfunction (and systolic HF)
Digoxin MOA and antiarrhythmic actions:
Shortens refractory period in atrial and ventricular myocardial cells = shortens atrial AP
—> Blocks Na+/K+ ATPase –> increases intracellular Na+ –> less drive for Ca2+ to leave cell –> increased intracellular Ca2+ –> increased contractility (positive inotrope)
Prolongs effective refractory period and diminishes conduction velocity in AV node (slows conduction in nodal tissue)
—> Direct AC node blocking effects and vagomimetic properties –> Inhibits Ca2+ currents in AV node and activates Ach-mediated K+ currents in atrium
Antiarrhythmic actions:
1) Slows AV conduction
2 Prolongs effective refractory period of AV node –> decreases the number of atrial impulses that are conducted through node –> increases PR interval
Digoxin clinical applications
Useful in treating atrial flutter and fibrillations:
1) Slows AV conduction
2 Prolongs effective refractory period of AV node –> decreases the number of atrial impulses that are conducted through node –> increases PR interval
Digoxin AE
Toxic doses:
- Alteration of color perception (yellow-green dues)
- Ectopic ventricular beats –> ventricular tachycardia and fibrillation
- GI effects: anorexia, N/V
- CNS effects: headache, fatigue, blurred vision
Adenosine
P1 receptor agonist
Enhances K+ conductance
Inhibits cAMP-mediated Ca2+ influx
Leads to hyperpolarization especially in AV node
Actions on AV node:
Decreases conduction velocity
Prolongs refractory period
Decreases automaticity
Increases PR interval
Adenosine PK, clinical applications and AE
Very short half life (15 seconds) so needs to be given via continuous IV infusion
DOC for abolishing acute supraventricular tachycardia
AE (low toxicity)
Bronchoconstriction in asthmatics
Flushing, burning
Chest pain (adenosine is released during MI so pain will be very similar but it is very short lived)
Magnesium MOA, effects on EKG and clinical applications
Functional Ca2+ antagonist
Acts on all myocardial cells –> increases QRS and PR intervals
Used to treat:
- Torsades de pointes (blocking Ca2+ currents prevents early afterdepolarisations)
- Digitalis-induced arrhythmia
- Prophylaxis of arrhythmia in acute MI
Atropine MOA and clinical uses
Decreases vagal tone and acts on nodal cells
Used to treat bradyarrhythmias (but most are treated with a pacemaker)
Antiarrhythmics that act on SA node (3)
b-blcokers (class II) Ca2+ channel blockers (class IV) Digoxin
Antiarrhythmics that act on AV node (4)
b-blockers
Ca2+ channel blockers
Digoxin
Adenosine
Antiarrhythmics that act on atrial myocytes (3)
Class IA (quinidine, procainamide, disopyramide) Class IC drugs (flecaindine, propafernone) K+ channel blockers (amiodarone, satolol, dofetilide)
Antiarrhythmics that act on ventricular myocytes (2)
Na+ channel blockers (all class I) K+ channel blockers (class III: amiodarone, satolol, dofetilide)
Antiarrhythmics that act on accessory pathways
Class IA Na+ channel blockers
K+ channel blockers
Treatment approaches to atrial fibrillation
Most common arrhythmia
Can be paroxysmal (intermittent) or persistent (chromic)
Focus mainly symptom control and prevention of long-term mortality and morbidity
1) Rhythm control: restore and maintain sinus rhythm
2) Rate control: control of ventricular rate while allowing atrial fibrillation to continue (slow conduction through AV node to prevent it from becoming v. fib which is life-threatening)
Rate control drugs for atrial fibrillation
All drugs increase PR interval –> want to slow conduction through AV node to control of ventricular rate –> use negative dromotropic agents
- Ca2+ channel blockers
- b-blockers
- Digoxin (in patients with reduced EF or CHF as it is a positive inotrope)
- Amiodarone (when other agents cannot be used)
Rhythm control drugs for atrial fibrillation
Induction and mainatence of sinus rhythm
- Class IC Na+ channel blockers (flecaindine, propafernone)
- Class III K+ channel blockers (amiodarone, satolol, dofetilide)
- Class IA act on atrial but never really used
- Class IB do not act on atria
Prevention of thromboembolic events with cardioversion
Heparin (IV) - given to unstable patients who require immediate cardioversion
Warfarin (oral) - given to stable patients where cardioversion would be delayed 3-4 weeks until adequate anti-coagulation has been achieved and
Oral anticoagulation should be continued for atlas 4 weeks after procedure as risk of stroke and MI is highest after the normal rhythm is stored as all the blood is going to be expelled from the heart and if there are any clots, they can travel to other areas and cause more damage
