Antiarrhythmics Flashcards
What is procainamide’s mechanism of action?
- potassium and sodium channel blocker
- depresses automaticity by decrease slope of phase 0 depolarization
- prevents reentry by converting unidirectional to bidirectional block
What are indications for use of procainamide?
- atrial fibrillation
- PVCs
- SVT
- VT
What are signs of procainamide toxicity?
- heart block
- hypotension
- myocardial depression
- QRS complex
- QT prolongation
- ventricular ectopy
What is the half life of procainamide?
- 3-4 hours
What is the metabolite of procainamide?
- N-acetyl procainamide (NAPA)
- half life of metabolite is 6-10 hours
- renally eliminated
- increased risk of side effects and QT prolongation
What are indications for use of quinidine?
- atrial fibrillation
- atrial flutter
- ventricular fibrillation
- ventricular tachycardia
What class does quinidine belong to?
- class 1A
What are signs and symptoms of quinidine toxicity?
- cinchonism
- loose stools
- QT prolongation
- thrombocytopenia
- ventricular tachycardia
What is the half life of quinidine?
- 6-8 hours
Quinidine is a potent ___________ inhibitor.
- CYP2D6
What class does disopyramide belong to?
- class 1A
- similar to quinidine without alpha effects
What are indications for use of disopyramide?
- atrial arrhythmias
- ventricular tachyarrhythmias
What are signs and symptoms of disopyramide toxicity?
- anticholinergic side effects (most significant)
- heart failure exacerbation
- QT prolongation
- thrombocytopenia
What is the half life of disopyramide?
- 6-7 hours
- renally eliminated
What class does lidocaine belong to?
- class 1B
What are indications for use of lidocaine?
- ventricular arrhythmias (especially re-entry dysrhythmias)
- ineffective against supraventricular arrhythmias
What are signs and symptoms of lidocaine toxicity?
- bradycardia
- CNS depression
- LV depression in patients with pre-existing disease
- nystagmus (early sign)
- seizure
What is the half life of lidocaine?
- 8 minutes
When should you use a reduced dose of lidocaine?
- CHF
- liver disease
True or False
Lidocaine undergoes significant first pass metabolism.
- true
What class does phenytoin belong to?
- 1B
What are indications for use of phenytoin?
- paradoxical ventricular tachycardia or torsades prolonged with prolonged QTc interval
- suppression of ventricular dysrhythmias associated with digitalis toxicity
What are signs and symptoms of phenytoin toxicity?
- death
- drowsiness
- nausea
- nystagmus
- respiratory arrest
- severe hypotension
- ventricular ectopy
- vertigo
What class does flecainide belong to?
- 1C
What are indications for treatment with flecainide?
- atrial tachyarrythmias
- PVCs
- WPW
What are the side effects of flecainide?
- difficulty with visual accommodation
- moderate negative inotropic effect
- vertigo
When should you avoid treatment with flecainide?
- CAD
- LV failure
- ventricular tachycardia
What are indications for treatment with beta blockers?
- atrial tachyarrhythmias
- slow ventricular response to atrial fibrillation and flutter
- SVT
What are signs and symptoms of beta blocker toxicity?
- acute bronchospasm
- asystole
- LV failure
- profound bradycardia
What class does amiodarone belong to?
- class III
What are indications for treatment with amiodarone?
- recurrent ventricular fibrillation or unstable ventricular tachycardia in patients unresponsive to other agents
- suppression of tachydysrhthmias associated with WPW
- termination of ventricular and supraventricular arrhythmias
What is the half life of amiodarone?
- prolonged to weeks to months in patients on oral agents
What drug interactions can occur with amiodarone?
- CYP3A4 substrate
- CYP3A4, CYP2C9 and PGP inhibitor
What are signs and symptoms of amiodarone toxicity?
- CV: bradycardia, dysrhythmias, heart block, heart failure, hypotension, sinus arrest
- Endo: hypothyroidism or hyperthyroidism
- Heme: coagulation abnormalities
- Hepatic: increased LFTs, liver failure
- Other: peripheral neuropathy, muscle weakness
- Respiratory: ARDS, pulmonary fibrosis
When is dronedarone contraindicated?
- Permanent atrial fibrillation
- decompensated heart failure
- medications that inhibit CYP3A4 or prolong QTc
- pregnancy
- significant liver disease
- second/third degree heart block
When is treatment with dronedarone indicated?
- atrial fibrillation
What class does verapamil belong to?
- class IV
What are indications for use of verapamil?
- slow ventricular rate in atrial fibrillation and flutter
- SVT
What are signs and symptoms of verapamil toxicity?
- asystole
- AV block
- bradycardia
- hypotension
- myocardial depression
What is diltiazem’s mechanisms of action?
- slow Ca+ channel blocking prolongs AV nodal conduction and refractoriness
What are indications for use of diltiazem?
- ventricular rate control in atrial fibrillation or atrial flutter
What are signs and symptoms of diltiazem toxicity?
- bradycardia
- constipation
- edema
- hypotension
What drug interactions can occur with diltiazem?
- potent CYP3A4 inhibitors, so MANY drug interactions
What are indications for use of digoxin?
- ventricular rate control in atrial fibrillation and flutter
- SVT
What is digoxin’s mechanism of action?
- inhibits sodium and potassium ATPase
- directly prolongs the effective refractory period in the AV node
- slows ventricular response rate in atrial fibrillation
- enhances conduction through accessory pathways
What are signs and symptoms of digoxin toxicity?
- can see any known rhythm disturbance
- PVCs common
- cardiac toxicity is enhanced with hypokalemia
What is adenosine’s mechanism of action?
- activates potassium channels that hyperpolarize nodal tissue causing a transient third degree AV block
- depression of the action potential in the AV and SA node
- Inhibits effects of increased cAMP, reduces calcium currents to increase AV note refractoriness
What are indications for use of adenosine?
- treatment of paroxysmal SVT that involves accessory pathways
What is the half life of adenosine?
- 1.5 seconds
What are signs and symptoms of adenosine toxicity?
- chest pressure (most common)
- dyspnea
- facial flushing
- can exacerbate bronchoconstriction in asthmatic patients
What are prodysrhythmic effects of antiarrhythmics?
- brady or tachyarrhythmias that represent new cardiac dysrhythmias associated with chronic antidysrhythmic drug treatment
How to antiarrhythmics promote torsades de pointes?
- potassium channel blockade may prolong QT interval and induce triggered activity in the ventricle
- class 1A and class III drugs block potassium channels and prolong QTc
Describe phase 0 of the action potential
- rapid depolarization
- increase in sodium conductance through ion channels
- leads to ventricular contraction
- ends with sodium channels becoming inactive at 65 mV
Describe phase 1 of the action potential
- sodium permeability is rapidly inactivated
- cell starts to repolarize
- potassium channels open and begin transient efflux
Describe phase 2 of the action potential
- plateau
- repolarization is delayed by an increase in conduction of calcium influx
- potassium channels open and maintain plateau through potassium efflux
Describe phase 3 of the action potential
- rapid repolarization
- complete repolarization due to inactivation of calcium conduction and increase in potassium permeability
- no significant movement of calcium or sodium
Describe phase 4 of the action potential
- spontaneous depolarization
- ATP dependent pumps move Ca+ and K+ ions to regain balance
How do action potentials vary between the muscle cell and the SA cell?
- pacemaker cells lack phase 1 and phase 2
- In muscle cells, phase 0 is mediated by Na+. In pacemaker cells, phase 0 is mediated by Ca+
What is the role of calcium channels in the action potential?
- responsible for phase 0 in SA and AV nodes
- contributes to phase 2 in ventricular contractile cells and prolongs refractory period
- affects phase 4 spontaneous depolarization
- facilitated by catecholamines
What is the role of sodium channels in the action potential?
- fast channels are sodium mediated
- responsible for phase 0
- rapid conduction velocity
What is impulse generation?
- automaticity
- cells that undergo spontaneous phase 4 depolarization are automatic and capable of impulse generation
Where can re-entry arrhythmias occur?
- SA node: SA nodal re-entry
- atrium: atrial tachycardia or flutter
- AV node: AV nodal re-entry and tachycardia mediated by accessory pathways
- ventricle: ventricular tachycardia
Where are sodium channels located in the heart?
- atria
- ventricles
Where are calcium channels located in the heart?
- AV node
- SA node
What are the 4 types of antiarrhythmics drugs?
- type I: sodium channel blockers
- type II: beta blockers
- type III: potassium channel blockers
- type IV: calcium channel blockers
What is the mechanism of action of sodium channel blockers?
- slows conduction
- prolongs QRS complexes in atria and ventricles
What is the mechanism of action of calcium channel blockers?
- slows the atrial rate
- slows conduction through the AV node (prolonging the PR interval)
What is the mechanism of action of potassium channel blockers?
- interrupts re-entry by slowing conduction or increasing the refractory period
- prolongs the QT interval
- induces triggered activity in the ventricle causing torsades de pointes
What are the 3 subclasses of class I (sodium channel blockers)?
- 1A
- 1B
- 1C
What drugs are class III antiarrhythmics?
- amiodarone
- bretylium
- dofetilide
- dronedarone
- ibutilide
- sotalol
What drugs are class IV of antiarrhythmics?
- diltiazem
- verapamil
What drugs are included in class II of the antiarrhythmics?
- beta blockers (except sotalol)
What drugs are included in class 1A of the antiarrhythmics?
- disopyramide
- moricizine
- procainamide
- quinidine
What drugs are included in class 1B of the antiarrhythmics?
- lidocaine
- mexilitine
- Phenytoin
What drugs are included in class 1C of the antiarrhythmics?
- flecainide
- propafenone
What is the effect of class 1A antiarrhythmics on the action potential?
- slows phase 0
- prolonged phase 3
What is the effect of class 1B antiarrhythmics on the action potential?
- slows phase 0
- shortens phase 3
What is the effect of class 1C antiarrhythmics on the action potential?
- creates a very slow phase 0
- no effect on phase 3
What is the effect of class II antiarrhythmics on the action potential?
- reduces slope of phase 4
What is the effect of class III antiarrhythmics on the action potential?
- prolongs phase 3
What is the effect of class IV antiarrhythmics on the action potential?
- reduces slope of phase 4
What is the mechanism of action of class 1 antiarrhythmics?
- blocks fast sodium channels with or without potassium channel blockade
- decreases depolarization rate and conduction velocity
What is the mechanism of action of class 1A antiarrhythmics?
- lengthens action potential duration and effective refractory period (sodium channel blockade)
- lengthens repolarization (potassium channel blockade)
What is the mechanism of action of class 1B antiarrhythmics?
- less powerful sodium channel blocker
- shortens the action potential duration and refractory period in normal cardiac ventricular muscle
What is the mechanism of action of class 1C antiarrhythmics?
- potent sodium channel blockers
- decreases rate of phase 0 depolarization and speed of conduction of cardiac impulses
- shortens duration of action potential in Purkinje fibers
- more prodysrhythmic effects
What is the mechanism of action of class II antiarrhythmics?
- decrease rate of spontaneous phase 4 depolarization
- slows conduction of cardiac impulses through atrial tissue
- slows heart rate
- prolongs PR interval
What is the mechanism of action of class III antiarrhythmics?
- blocks potassium ion channels
- prolongs cardiac depolarization, action potential duration and effective refractory period
What is the mechanism of action of class IV antiarrhythmics?
- calcium channel blockers
- inhibit inward slow calcium currents
What factors reduce automaticity?
- vagal influences
- digitalis drugs
- parasympathomimetic drugs
- halothane
True or False
Factors that reduce automaticity at higher pacemaker sites will passively favor the movement of the pacemaker to the lower sites.
- true
Amiodarone and sotalol block what receptors?
- sodium channels
- beta blockade
- calcium channel blockade
What type of syndrome is possible with chronic administration of procainamide?
- systemic lupus erythematous
What effect can digoxin have on WPW?
- can increase the ventricular response in WPW
- enhances conduction through accessory pathways
When does adenosine not work?
- no effect on arrhythmias originating distal to the AV node
- not effective in treatment of atrial fibrillation or flutter
Disopyramide is similar to _____, but without the ____ effects
- Quinidine
- Alpha
Calcium channel blockers reduce slope of phase ____
4
What is more common with amiodarone toxicity, hypo or hyper thyroidism?
Hypothyroidism
T/F
Amiodarone has an antiadrenergic effect that causes competitive blockade of alpha and beta receptors.
FALSE
causes noncompetitive blockade of alpha and beta receptors
T/F
Beta blockers can only be used for atrial arrhythmias
True
What is an advantage of MULTAQ over amiodarone?
Has no iodine, so no risk of thyroid abnormalities
T/F
Adenosine may exacerbate bronchoconstriction in asthmatic patients
True
What non-cardiac med has the highest risk of torsades?
Haldol
Antipsychotics are #1
Antibiotics are #2
What are 2 drawbacks to using Ibutilide/Dofetilide?
- Very expensive (so tight dispensing laws
- Very high incidence of torsades and ventricular arrhythmias
Which subclass of Class I antidysrhythmics is the least powerful sodium channel blockers?
IB
IC is the most powerful (so assoc. with more prodysrhythmic effects)
Which two meds are basically “phase all” bc they work everywhere on the action potential?
Amiodarone and sotalol
Which class IA med has some evidence of alpha blockade and vagal inhibitor?
Quinidine
____ is basically “mini quinidine” and used in the treatment of pseudobulbular effect and alzheimers
Neudexa
What is the most significant side effect of disopyramide?
Anticholinergic effects
Disopyramide is similar to quinidine but without the ____ effects
alpha
What class is the most pro-arrhythmic of all anti-arrhythmics?
1C
Which anti-arrhythmic has the highest risk of arrhythmias?
Flecainide
What is a major side effect with Verapamil toxicity?
Hypotension
Adenosine affects ___ in the ___ node and ___ in the heart cells
- calcium
- AV
- potassium
What EKG change would be seen after giving adenosine?
Third degree heart block
T/F
Amiodarone causes acute renal failure and electrolyte abnormalities
FALSE
it DOES NOT cause ARF and lyte abnormalities
During the action potential, sodium channels go from ___ to ___ to ____
- “closed”
- “open”
- “inactive”
The action potential ends with sodium channels becoming “inactive” at ___ mV
+65mV
In cardiac pacemaker cells (SA and AV), phase O is mediated by ____
- Calcium
In cardiac muscle cells (atrium and ventricle), phase 0 is mediated by ____
- Sodium
What percentage of patients become ANA positive from Procainamide?
50-80%
T/F
Procainamide is a myocardial depressant
True
T/F
Quinidine is a potent CYP2D6 inhibitor and can lead to a build up of dextromorphan
True
What EKG change will you see with all 1a’s?
QT prolongation
What is the most common indication for beta blockers?
Afib
What electrolyte mediates beta blockers?
Calcium
What EKG changes will you see with amiodarone?
Prolongs PR, QRS, and QT intervals
What are 2 respiratory problems assoc. with amiodarone?
Pulmonary fibrosis and ARDS
What clinical presentation would see if you from iodine buildup with Amiodarone?
Tips of ears and nose turn blue
Esp if already taking synthroid
T/F
In rate vs rhythm control for Afib, there is no difference in mortality outcomes in using rhythm control with amiodarone and ???
True
T/F
If you use verapamil on a pt with accessory pathways, you can exacerbate an re-entry arrhythmia
True
Verapamil has NO effect on accessory tracts
What is the most common sign of digoxin toxicity?
PVC’s
Cardiac toxicity from Digoxin is enhanced with _____
hypokalemia
T/F
Digoxin can be used to convert Afib to NSR
FALSE
Digoxin will only slow the rate down, will not convert
What receptor does Adenosine work on in the heart?
A1 (Adenosine receptor)
T/F
Adenosine has effects on arrhythmias originating distal to the AV node
FALSE
No effect on arrhythmias originating distal to the AV Node.
What are the 3 most common arrhythmias that can be caused by anti-arrhythmics?
- Torsades de pointes.
- Increased ventricular tachycardias (esp with AV blockers).
- Wide complex ventricular rhythm.
What is the pathophysiology of torsades assoc. with anti-arrhythmics?
K channel blockade may prolong the QT interval and induce triggered activity in the ventricle causing polymorphic VT or ventricular fibrillation.
Which two classes of anti-arrhythmics can most likely cause torsades?
IA and III
They both block K+ channels and prolong QTc intervals
Torsades occurs in ___% of patients who receive QT prolonging drugs
1-8%
What two classes of anti-arrhythmics are most likely to precipitate incessant ventricular tachycardia?
Ia and Ic
Both have fallen out of favor due to this
What two volatile anesthetics are most likely to cause QT prolongation and torsades?
Isoflurane and enflurane
What class of anti-arrhythmics is most likely to cause wide complex ventricular rhythm?
Ic
What is the voltage of the action potential at the beginning of phase 0?
- negative 70 mV
T/F
In phase 4 of the action potential, ATP-dependent pump moves calcium and potassium ions to regain balance
True
What 4 conditions predispose a patient to developing torsades?
- Hypomagnesemia
- Hypokalemia
- Slow heart rate
- Preexisting QT prolongation
