Drugs used in Cardiac Arrhythmias - Konorev Flashcards
What channels allows for the phase 4 of the Pacemaker AP?
Funny current, I(f) channels; and slow Ca++ influx T-type channels
what factors determine the firing rate, or automaticity of the pacemaker cells?
- rate of spontaneous depolarization in phase 4 (i.e. the slope): decreased slope = decreased rate thus need more time to reach threshold
- Threshold potential - the potential at which AP is triggered
- Resting potential - if potential is less negative, less time is needed to reach the threshold- firing rate increase
Class 1 antiarrhythmic drugs block what channel?
Sodium channel
what are the different categories of drugs in Class 1 antiarrhythmic ?
1A, 1B and 1C
Quinidine, procainamide and Disopyramide are what class of drugs?
Class 1A antiarrhythmia
Lidocaine and mexiletine are what class of drugs?
Class 1B antiarrhythia
Flecainide and propafenone are what class of drugs?
Class 1C antiarrhythmia
What class of drugs belong to the following class of antiarrhythmic drugs A. Class 2 B. Class 3 C. Class 4 D. Miscellaneous / class 5
Class 2: Beta blockers (esmolol, propranolol)
Class 3: Potassium channel blocker (amiodarone, dronedarone, sotalol, dofetilide, ibutilide)
Class 4: Cardioactive CCB (verapamil and diltiazem
Miscellaneous agent: adenosine
What is the MOA of class 1A drugs?
- Block Na channels, slow impulse conduction, reduce automatism of latent pacemakers.
- Use-dependent block - preferentially bind to open (activated) Na channels and so ectopic pacemaker cells with faster rhythms will be preferentially targeted and thus phase 0 slope will be decreased.
- K channel is also blocked and this causes prolongation of AP duration and prolongs QRS and QT intervals on EKG
What is the MOA of class 1B drugs?
- use dependent block - bind to inactivated Na channels and so preferentially bind to depolarized cells.
- dissociate from channel with fast kinetics - no effect on conduction in normal tissues.
- shortens AP
- More specific action on Na channel - (do NOT block K channel, do not prolong AP or QT duration on EKG)
What is the MOA of class 1C drugs?
- Blocks Na channel, slow impulse conduction
- preferentially bind to open (activated) Na channel
- Dissociate from the channel with slow kinetics
- Block certain K channels
- Do not prolong action potential duration and QT interval duration of the ECG
- Prolong QRS interval duration
what is the normal sympathetic effect on the pacemaker action potential?
- Increase slope of phase 4 due to effects on I(f) and T-type Ca channel
- Reduced threshold due to effect on L type Ca channel
- AP occurs sooner.
What is the MOA of propranolol and esmolol as a class 2 antiarrhythmic drug?
- Slows action potential (blocks I(f) and T-type Ca channel, and by Increasing threshold due to effect on L-type Ca channel); this effect on SA node thus decreases HR (increases RR interval)
- Ventricular myocardium: decrease Ca2+ overload, prevent delayed afterdepolarization
- Increase PR interval
What is the MOA of class 3 antiarrhythmic drug K channel blocker?
- Blocks potassium channels, which prolongs action potential duration and QT interval on ECG. Most effective at slow heart rates
- Prolongs refractory period
what is the MOA of class 4 antiarrhthmic drugs (CCB: verapamil/diltiazem)?
- Block both activated and inactivated L-type Ca channel
- active in slow response cells - decrease the slope of phase 0 depolarization
- slow SA depolarization, cause bradycarida
- prolong action potential duration and refractory period in AV node
- Prolong AV node conduction time
- May suppress delayed afterdepolarizations- amy be effective in DAD-induced ventricular arrythmias.
Which Class 1A drug has antimuscarinic activity is used to treat sustained ventricular tachycardias, and may be used in arrhythmias associated with MI. It’s action on ganglions may cause hypotension
Procainamide. It directly depresses the activities of SA and AV nodes.
- Has ganglion-blocking properties, reduces peripheral vascular resistance and may cause hypotension
Explain how sympathetics increase HR.
Beta 1 –> increased AC –> increased cAMP –> increased funny channel flow rate and decreased calcium channel threshold –> increased pacemaker speed.
Explain how parasympathetic slows heart rate
M2 –> decreased AC and increased K opening –> slow funny current, higher threshold (via less cAMP/PKA for Ca channel), and lower resting potential
What causes an early afterdepolarization?
Afterdepolarization is another rapid depolarization during phase 2 and 3 of the previous AP. this is caused by impaired K channels and prolonged repolarization period
Torsades de pointes is commonly seen in _
Long QT syndrome (prolonged repolarization)
Which antiarrhythmic drugs are long-QT inducing?
Class 1A or Class 3
What is a delayed afterdepolarization?
Another partial depolarization during phase 4 (hyperpolarized). Due to increased cytosolic Ca++.
What are some indication for procainamide?
- WPW, PAC, PVC, A-fib, V-tach, A-flutter
what AE are associated with procanamide?
- QT interval prolongation
- Induction of torsade de pointes arrhythmias and syncope
- excessive inhibition of conduction
- Lupus syndrome with arthritis, pleuritis, pulmonary disease, hepatitis and fever
- nausea/diarrhea
- agranulocytosis
What are some indication for Quinidine
- Restore rhythm in a-fib/flutter pts with noral to arrhythmic hearts.
- Sustained ventricular arrhythmia (MAT, PAC, PVC, V-tach)
What AE are associated with quinidine
- QT interval prolongation
- Torsade de pointes and syncope
- excessive slowing of conduction
- GI effects
- HA/dizziness/tinnitus
- thrombocytopenia, hepatitis, fever
Disopyramide is used for
treatment of recurrent V-arrhythmias
what AE are associated with disopyramide
- QT interval prolongation,
- Torsade de pointes
- syncope
- negative inotropic effect – > HR
- excessive depression of cardiac conduction
- Atropine-like symptoms: Urinary retention, dry mouth, blurred vision, constipation, exacerbation of glucoma
What is the MOA of lidocaine?
- blocks inactivated Na channel (use dependence) - selectively blocks conduction in depolarized tissue, making damaged tissue completely electrically silent
- rapid kinetics so dissociates fast and has no effect on cardiac conductivity in normal tissue.
What is the indication for lidocaine?
- mono and polymorphic ventricular tachycardias. esp useful in arrhythmia after MI.
What adverse effects are associated with lidocaine?
This is the least toxic Class 1 drugs
- CV: hypotension in pts w/ HF
- Neuro: paresthesias, tremor, slurred speech, convulsion
What is mexiletine used for?
V-arrhythmias
- relieve chronic pain, esp pain due to DM neuropathy and nerve injury
What AE are associated with mexiletine?
- tremor
- blurred vision
- nausea
- lethargy
What is Flecainide used for?
In pts with normal hearts to treat SVA including AF, PSVT (AVNRT, AVRT)
- Life threatening V-arrhythmias, such as sustained V-tach
What AE are associated with Flecainide?
Severe exacerbation of V-arrhythmia when given to pts with: preexisting Vtach, MI, or V-ectopic rhythms
What is propaenone used for?
Prevent paroxysmal AF and SVT in pts w/o structural disease
- sustained Varrhythmias
What AE are associated with Propafenone?
- Exacerbation of V-arrythmias
- metallic taste
- constipation
Propafenone should not be combined with what hepatic enzyme inhibitors as the risk of proarrhythmia may be increased?
CYP2D6 and CYP3A4
What is the indication of propranolol?
- Arrhythmias associated with stress
- re-entrant arrhythmias that involve AV node (AVNRT, AVRT)
- A-fib and flutter
- Arrhythmias associated with MI
What class 2 drug is short acting (10mins) and is used as continuous iv infusion with rapid onset and termination of its action
Esmolol
What is esmolol used for?
- SVA
- arrhythmias associated with thyrotoxicosis
- Myocardial ischemia or AMI with arrhythmia
- used as adjunct in general anesthesia to control arrhythmias in perioperative period
1 blocks potassium channels, but also has adrenolytic activity (causes peripheral vasodilation) and is known to block inactivated Na channel; causes bradycardia, slows AV conduction
Amiodarone
Amiodarone is used for
V-arrhythmia.
- A-fib (not FDA approved)
_ is known to have maintained drug effects even 1-3 months after discontinuation
Amiodarone
What AE are associated with amiodarone?
- AV block and bradycardia
- Fatal pulmonary fibrosis
- hepatitis
- photodermatitis, deposits in skin, blue grey skin discoloration in sun exposed areas
- optical neuritis: deposit of drugs in places like cornea and other eye tissues
- Blocks thryoxine to Triiodothyroine –> hypo or hyperthyroidism
what is the dronedarone?
1 Blocks multiple K channels;
- Block Na current
- Blocks L-type Ca current
- Prolongs AV refractory period and PR interval
- stronger antiadrenergic effects than amiodarone
what is dronedarone used for?
A-fib/flutter. Not as effective as amiodarone in maintaing sinus rhythm
What AE are associated with dronedarone?
- Worsen HF
- GI issues
- not as severe AE as amiodarone (no iodine moiety, shorter half life, less drug interaction)
Dronedarone is contraindicated in pts with _
decompensated HF
what is sotalol used for?
It is a Class 3 antiarrhythmic drug (K channel blocker) that is used to treat life-threatening ventricular arrhythmias and maintenance of sinus rhythm in pts with afib.
what AE are associated with sotalol (Class 3 antiarrhythmic drug Channel blocker)
depression of cardiac function, provokes torsade de pointes
what is the MOA of dofetilide?
- blocks rapid component of the delayed rectifier potassium current- effect is more pronounced at lower heart rates.
What antiarrhythmic clas 3 drug is eliminated by the kidney and a very narrow therapeutic window and thus dose needs to be adjusted based on creatinine clearance.
Dofetilide
what is the indication for dofetilide?
Converts AF to sinus rhythm and maintain sinus rhythm after cardioversion
what AE is associated with Dofelitide?
QT interval prolongation and increased risk of ventricular arrhythmias
what are cardioactive CCB (class 4 antiarrhythmic) used for?
- prevention of paroxysmal SVT
- rate control in AF and atrial flutter
what adverse effects are associated with CBB’s used as antiarrhythmics?
- negative inotrophy
- AV block
- SA node arrest
- bradyarrhythmias
- Hypotension
_ constipation (verapamil)
What is the MOA for adenosine?
- Activates K current and inhibits Ca and funny currents, causing marked hyperpolarization and suppression of action potentials in pacemaker cells.
- inhibits AV conduction and increase nodal refractory period
What is adenosine used for?
conversion to sinus rhythm in Paroxysmal SVT
What AE are associated with adenosine?
- SOB
- Bronchoconstriction
- chest burning
- AV block
- Hypotension
what drugs or classes or drugs are known to cause long QT syndrome and torsade de pointes arrhytmias?
- Antiarrhythmic drugs - classes 1A and 3 (amiodarone very rarely induces TdPs)
Digoxin induced arrhthmias (tachy and ectopic rhythms) is a type of triggered activity resulting from delayed afterdepolarization which occurs during phase_1_ , as a result of increased cytosolic 2 due to it’s overload. This overload is primarily spontaneous release of 3 from SR which activates 4 exchange leading to a net depolarizing current.
- 4
- Ca++
- Ca++
- 3Na/Ca
Explain the mechanism of digoxin-induced bradyarrhythmia
Central parasympathominetic activity and accentuation of vagal effects on the heart
How is digoxin-induced arrhythmias treated?
Cancel digoxin
anti-digoxin ab (digibind, digifab)
- K supplement to upper normal levels
Both sotalol and esmolol are beta blockers but they are in different categories of antiarrhythmic drugs. which one is known to prolong QT interval?
Sotalol. It’s a K channel blocker and thus prolong AP duration and AT interval on ECG and prolongs refractory period.
Slowing of atrioventricular conductivity is likely done by diltiazem or nifedipine?
Diltiazem
Pt develops sinus bradycardia, what drug is known to be safe and effective in normalizing HR in these type of patients?
Atropine
With the use of quinidine, indicate what changes are seen in:
A. PR interval
B. QRS interval
C. QT interval
A. slight decrease (quinidine is known to have antimuscarinic effect thus enhance AV conductance)
B. moderate increase
C. greater increase.
A pt with afib has a rate of 280/min with a ventricular rate of 140 with a 2:1 nodal transmission. After tx with a drug the atrial rate slowed to 180 but the ventricular rate also increased to 180. Which drug was most likely given?
Disopyramide (class 1A)
