Antiarrhythmic Drugs (Konorev) Flashcards
Cardiac _______ _______ is a sequence of ion fluxes through specific ion channels across the cell membrane (sarcolemma).
Action Potential
What components of cardiac muscle are involved in fast action potential?
- Ventricular contractile cardiomyocytes
- Atrial cardiomyocytes
- Purkinje fibers
What components of cardiac muscle are involved in slow (pacemaker) action potential?
- SA node cells
- - AV node cells
What fast action potential phase is being described?
– Voltage-dependent fast Na+ channels open as a result of depolarization; Na+ enters the cells down its electrochemical gradient.
Phase 0
What fast action potential phase is being described?
– K+ exits cells down its gradient, while fast Na+ channels close, resulting in some depolarization.
Phase 1
What fast action potential phase is being described?
– Plateau phase results from K+ exiting cells offset by and Ca2+ entering through slow voltage-dependent Ca2+ channels.
Phase 2
What fast action potential phase is being described?
– Ca2+ channels close and K+ begins to exit more rapidly resulting in repolarization.
Phase 3
What fast action potential phase is being described?
– Resting membrane potential is gradually restored by Na+/K+ ATPase and the Na+/Ca2+ exchanger.
Phase 4
What pacemaker action potential phase is being described?
– Slow spontaneous depolarization
Phase 4
For phase 4 of pacemaker action potential, there is poorly selective ionic influx of Na+ and K+, known as pacemaker current called ________ ________. This is activated by hyperpolarization.
Funny Current (If)
For phase 4 of pacemaker action potential, there is also slow Ca2+ influx via _______ channels.
T-type (transient)
What pacemaker action potential phase is being described?
– Upstroke of action potential due to Ca2+ influx through the relatively slow L-type (long-acting) Ca2+ channels.
Phase 0
***Remember, this occurs due to calcium and NOT sodium like in fast AP!
What pacemaker action potential phase is being described?
– Repolarization due to inactivation of calcium channels with increased K+ efflux.
Phase 3
Class 1 antiarrhythmic drugs are ________ channel-blockers.
Sodium
What are the Class 1A drugs?
- Quinidine
- Procainamide
- Disopyramide
What are the Class 1B drugs?
- Lidocaine
- - Mexiletine
What are the Class 1C drugs?
- Flecainide
- - Propafenone
Class 2 anti arrhythmic drugs are…
Beta blockers
What are the Class 2 drugs?
- Esmolol
- - Propranolol
Class 3 anti arrhythmic drugs are ________ channel-blocking drugs.
Potassium
What are the Class 3 drugs?
- Amiodarone
- Sotalol
- Dofetilide
- Ibutilide
Class 4 anti arrhythmic drugs are cardioactive ________ channel blockers.
Calcium
What are the Class 4 drugs?
- Verapamil
- - Diltiazem
This is an anti arrhythmic drug that is not in one particular class because it has characteristics of many of them.
Adenosine
When a sodium channel is activated, Na+ current occurs down ________ and ________ gradients.
Electric
Concentration
Class 1A drugs block sodium channels, which slow impulse conduction and reduce automatism of ectopic pacemakers. Explain what this looks like on ECG.
Prolong QRS interval of ECG
Class 1A drugs reduce the slope of which phase?
Phase 0
Class 1A drugs can also block ________ channels, which prolongs the action potential duration.
Potassium
Since Class 1A drugs can also block potassium channels and thus prolong the action potential duration, what does this look like on an ECG?
Prolongs QT interval of ECG
This Class 1A drug, in addition to sodium channel block, can directly depress the activities of SA and AV nodes and possesses antimuscarinic activity. Also reduces peripheral vascular resistance and may cause hypotension.
Procainamide
This Class 1A drug is used infrequently due to its frequent dosing and common occurrence of lupus-related side effects.
Procainamide
This Class 1A drug has the following adverse effects:
– QT interval prolongation and induction of torsade de pointes arrhythmias and syncope
– Lupus erythematous syndrome
– Hypotension
Procainamide
This Class 1A drug is a natural alkaloid from Cinchona bark. Rarely used due to its cardiac and extra cardiac adverse effects and availability of better drugs.
Quinidine
This Class 1A drug, in addition to sodium channel block, affords antimuscarinic effect on the heart and may enhance AV conductance. This may cause hypotension and tachycardia.
Quinidine
This Class 1A drug has the following adverse effects:
– QT interval prolongation and induction of torsade de pointes arrhythmia and syncope
– GI side effects
– Cinchonism (tinnitus, hearing loss, confusion, delirium, psychosis, vision issues)
– Thrombocytopenia, hepatitis, fever
Quinidine
This Class 1A drug, in addition to the sodium channel block, affords strong antimuscarinic effect on the heart. It is used clinically for recurrent ventricular arrhythmias.
Disopyramide
This Class 1A drug has the following adverse effects:
– QT interval prolongation and induction of torsade de pointes arrhythmia and syncope
– Negative inotropic effect (may precipitate heart failure)
– Atropine-like symptoms (tachycardia, urinary retention, dry mouth, blurred vision, constipation, exacerbation of glaucoma)
Disopyramide
Class 1B drugs also bind to inactivated sodium channels. What is the difference in conduction that they cause for normal vs. depolarized (damaged) tissue?
Normal tissue = no effect on conduction
Depolarized (damaged) tissue = slows conduction (decreased slope for phase 0)
This subtype of Class 1 drugs may shorten the action potential, and are more specific for action on sodium channels. They do not block potassium channels, do not prolong action potential or QT duration on ECG.
Class 1B drugs
This Class 1B drug has an extensive first-pass metabolism and is used only by the intravenous route.
Lidocaine
What is the clinical use for Lidocaine (in terms of arrhythmia)?
Termination of ventricular tachycardia in the setting of acute myocardial ischemia
This Class 1B drug is the least toxic of all Class 1 drugs, proarrhythmic effects are uncommon.
Lidocaine
This Class 1B drug is the orally active congener of Lidocaine. It has electrophysiological and antiarrhythmic effects similar to Lidocaine as well.
Mexiletine
What is the clinical use for Mexiletine?
– Ventricular arrhythmias
– Relieve chronic pain, especially due to diabetic neuropathy and nerve injury
This Class 1B drug has the following adverse effects:
- Tremor
- Blurred vision
- Nausea
- Lethargy
Mexiletine
This subtype of Class 1 drugs will block sodium channels, thus slowing impulse conduction. They also block certain potassium channels.
Class 1C drugs
This subtype of Class 1 drugs does NOT prolong action potential duration and QT interval duration of the ECG, but it does prolong the QRS interval duration.
Class 1C drugs
***Prolonged QRS means decreased slope of Phase 0, resulting in slower conduction.
What is the clinical use for Flecainide, a Class 1C drug?
– In patients with otherwise normal hearts who have supraventricular arrhythmias
– Life-threatening refractory ventricular arrhythmias
Flecainide may cause severe exacerbation of ventricular arrhythmias when administered to what type of patients?
– Patients with preexisting ventricular tachyarrhythmias
– Patients with previous MI
– Patients with ventricular ectopic rhythms
Propafenone has similar sodium channel blocking kinetics as Flecainide. It also possesses weak _________ activity.
Beta-blocking
What is the clinical use for Propafenone?
Supraventricular arrhythmias in patients without structural disease
T/F. Propafenone has similar side effects to Flecainide.
True. It also can exacerbate ventricular arrhythmias.
Briefly explain how sympathetics usually work on cardiac pacemaker cells.
Beta1-adrenergic receptor is a GPCR, which will activate cAMP then PKA. PKA will go on to activate the funny current (If) and the T- and L-type Ca2+ channels. This results in increased HR and contractility.
***Thus, Beta-blockers obviously block the receptor and prevent this from happening.
Sympathetics cause an (INCREASED/DECREASED) slope due to effects on funny current and T-type Calcium channels. There is also an (INCREASED/DECREASED) threshold due to effect on L-type Calcium channels.
Increased
Decreased
***Increased slope means faster depolarization, and lowered threshold means reaching depolarization quicker as well.
***Beta blockers have the exact opposite effect!
Beta-blockers have anti arrhythmic actions that are mediated by the effects of these drugs on the pacemaker action potential. What do these drugs do to the SA node and AV node?
SA node – decrease HR (increase RR interval)
AV node – decrease AV conductance (increase PR interval)
Beta-blockers will cause an (INCREASED/DECREASED) slope due to effects on funny current and T-type Calcium channels. They will also cause an (INCREASED/DECREASED) threshold due to the effect on L-type Calcium channels.
Decreased
Increased
What is the mechanism of action for Class 2 drugs?
Beta-blockers
This Class 2 drug is used clinically for cardiac arrhythmias associated with stress and thyroid storm.
Propranolol
Which Class 2 drug would be best suited for the following?
- Atrial fibrillation and flutter
- Paroxysmal supraventricular arrhythmias
- Arrhythmias associated with MI (decreases mortality)
Propranolol
This Class 2 drug is a short-acting selective Beta-1 blocker.
Esmolol
Esmolol has a half-life of _______ due to hydrolysis by blood esterases.
10 min
Which Class 2 drug would be best suited for the following?
- Supraventricular arrhythmias
- Arrhythmias associated with thyrotoxicosis
- Myocardial ischemia or acute MI with arrhythmias
- As adjunct drug in general anesthesia to control arrhythmias in preoperative period
Esmolol
What are adverse effects of beta-blockers (Class 2 drugs)?
- Reduced CO
- Bronchoconstriction
- Impaired liver glucose mobilization
- Produce unfavorable blood lipoprotein profile (increase VLDL and decrease HDL)
- Sedation, depression
- Withdrawal syndrome associated with sympathetic hyperresponsiveness
What are contraindications for the use of beta-blockers (Class 2 drugs)?
- Asthma
- Peripheral Vascular Disease
- Raynaud’s Syndrome
- Type 1 diabetics on insulin
- Bradyarrhythmias and AV conduction abnormalities
- Severe depression of cardiac function
Class 3 drugs are _________ channel blockers, which regulates action potential.
Potassium
For Class 3 drugs, voltage-gated rapid and slow delayed rectifier K+ channels contribute to regulation of action potential. They are responsible for _________ of the cell membrane during action potential. They also limit the frequency of action potentials by regulating the duration of the ________ ________.
Repolarization
Refractory period
Class 3 drugs block potassium channels, thus prolonging the _______ _______ duration.
Action potential
Class 3 drugs will prolong the ________ on ECG, and prolong the refractory period.
QT interval
This Class 3 drug is one of the most widely used because it also has characteristics of Class 1, 2, and 4 drugs.
Amiodarone
What drug is being described by the following pharmacodynamics?
- Blocks potassium channels
- Prolongs QT interval and APD uniformly over wide range of heart rates
- Blocks inactivated sodium channels
- Possesses adrenolytic activity
- Calcium channel blocking activity
- Causes bradycardia and slows AV conduction
Amiodarone
What is the clinical use of Amiodarone?
- Recurrent ventricular tachycardia
- - Atrial fibrillation
With the use of Amiodarone, the incidence of this adverse effect is much lower as compared to other Class 3 drugs.
Torsade de pointes
What are adverse effects of the skin that can occur with Amiodarone?
- Photodermatitis
- Deposits in skin
- Blue-grey skin discoloration in sun-exposed areas
What are adverse effects of the eyes that can occur with Amiodarone?
- Deposits of drug in cornea and other eye tissues
- - Optical neuritis
How can Amiodarone cause hypo- or hyperthyroidism?
Blocks peripheral conversion of thyroxine to triiodothyronine
Which class 3 drug would have these adverse effects?
- AV block and bradycardia
- Fatal pulmonary fibrosis
- Hepatitis
Amiodarone
This Class 3 drug prolongs APD, but also has Class 2 characteristics as a non-selective beta-blocker.
Sotalol
What is the clinical use for Sotalol?
- Treat life-threatening ventricular arrhythmias
- - Maintenance of sinus rhythm in pts with A fib
What are the adverse effects of Sotalol?
- Depression of cardiac function
- - Provokes torsade de pointes
These Class 3 drugs specifically block rapid component of the delayed rectifier potassium current.
Dofetilide
Ibutilide
What is the clinical use for the Class 3 drugs Dofetilide and Ibutilide?
– Restore sinus rhythm in patients with A fib
– Maintain sinus rhythm after cardioversion in patients with A fib (Dofetilide ONLY)
What are the adverse effects of Class 3 drugs Dofetilide and Ibutilide?
QT interval prolongation and increased risk of ventricular arrhythmias
Class 4 drugs block what channels?
L-type Calcium channels
***These are similar to Na+ channels in fast action potential – this is pacemaker action potential
Class 4 drugs are active in cells exhibiting pacemaker potential. They will (INCREASE/DECREASE) the slope of phase 0 depolarization and (INCREASE/DECREASE) the L-type Calcium channel threshold potential.
Decrease
Increase
Overall, Class 4 drugs work by slowing the _______ ______ depolarization to reduce heart rate. This in turn prolongs conduction time and refractory period in the ______ ______.
SA Node
AV Node
These Class 4 drugs are used for:
– Termination and prevention of paroxysmal supraventricular tachycardia
– Ventricular rate control in atrial fibrillation and flutter
Verapamil
Diltiazem
The Class 4 drugs Verapamil and Diltiazem have the following cardiac effects:
- Negative inotrophy
- AV block
- SA node arrest
- Bradyarrhythmias
- Hypotension
What is the extracardiac adverse effect of Verapamil?
Constipation
Adenosine is a miscellaneous drug agent used to activate A1 adenosine receptors, which is what type of receptor?
GPCR - Gi (inhibitory)
By activating the A1 adenosine receptors, this enhances the ________ current and inhibits _______ and ______ currents. This causes marked hyperpolarization and suppression of action potentials in pacemaker cells.
Potassium
Calcium
Funny
Adenosine also inhibits ______ conduction and increases _______ nodal refractory period.
AV
AV
This drug is used clinically for conversion to sinus rhythm in paroxysmal supraventricular tachycardia. It is given intravenously to provide rapid relief.
Adenosine
What are adverse effects of Adenosine?
- SOB
- Bronchoconstriction
- Chest burning
- AV block
- Hypotension
