Flashcards in EXAM #1: CV PHARM 2 Deck (50):
What are the three consequences of arrhythmia?
1) Compromise of mechanical performance
2) Arrhythmogenesis/ evolution
Note that decreased mechanical performance of the LV leads to a direct decrease in SV and CO.
What are the four general mechanisms that anti-arrhythmic drugs decrease spontaneous activity of the heart?
1) Decrease phase 4 slope
2) Increase threshold
3) Increase maximum diastolic potential
4) Increase action potential duration (ADP) i.e. effective refractory period
What is the maximum diastolic potential?
The absolute value of the repolarization--deepening (called increase) this will DECREASE spontaneous activity
What does increasing the action potential duration do to the ERP/ADP ratio?
Decreases the ERP/ADP ratio-->arrhythmothgenic
What are the two ways to increase refractoriness?
1) Na+ channel blockers, which increase the effective refractory period
2) Increase AP duration with K+ channel blockers
Why do Na+ channel blockers increase the ERP?
Blocking Na+ channels shifts the voltage dependence of recovery and delays the point to which 25% of the channels have recovered
Why do K+ channel blockers increase the action potential duration?
Decrease phase 3 re-polarization b/c of less K+ efflux
What is the general mechanism of action of the Class I antiarrhythmics?
Blockade of fast inward Na+ channels in conductive tissues of the heart
What are the physiologic effects of Class I antiarrhythmics?
Blockade of the fast inward Na+ channels:
1) Decreases the maximum depolarization rate of Phase 0
2) Slows intracardiac conduction
How does the channel specificity of Class Ia antiarrhythmics change with increasing dose?
1) Moderate binding to Na+ channels
2) K+ channel blockade
3) Ca++ channel blocking at high doses
What are the general physiologic effects of the Class Ia antiarrhythmics at increasing doses?
1) Na+ moderately slows Phase 0
2) K+ delays Phase 3 and prolongs the QRS/QT interval
3) Ca++ blockade depresses Phase 2 in myocardial tissue and Phase 0 in nodal tissue
What are the Class Ia antiarrhythmics?
What is the primary mechanism of action of Quinidine and its associated effects? What are the ancillary mechanisms of action of Quinidine?
Primary MOA is to block rapid inward Na+ channel, which:
- Decreases Vmax of Phase 0
- Slows conduction
- Block K+ channels-->increasing QT interval
- Blocks M receptors-->increasing HR
- Alpha antagonist-->decrease BP
What are the indications for Quinidine?
Only used in refractory patients to:
- Conversion of symptomatic a-fib or a-flutter
- Prevent recurrence of a-fib
- Treat documented life-threatening ventricular arrhythmias
What are the adverse effects of Quinidine?
1) Cinchonism (tinnitus)
3) Torsades de Pointes
What is cinchonism?
This is a triad of symptoms seen from quidine overdose or its natural source, cinchona bark, including:
- Blurred vision
What is the mechanism of action of Procainamide?
1) Blocks rapid inward Na+ channels, which decreases the Vmax of Phase 0
2) Blocks K+ channels, which will prolong the APD
What are the physiologic effects of Procainamide?
Decreased conduction, automaticity, and excitability
How does Procainamide compare to Quinidine?
Procainamide > Quinidine b/c it has:
- No effect on muscarinic receptors
- Does antagonize alpha receptors i.e. no hypotension
What are the clinical indications for Procainamide?
1) Life-threatening ventricular arrhythmias
2) Re-entrant SVT
4) A-flutter with WPW
What is the pharmacokinetic pearl to remember about Procainamide?
IV loading takes 20 minutes i.e. this is NOT a good agent to treat ventricular arrhythmia acutely
What are the cardiac adverse effects associated with Procainamide?
Arrhythmia aggravation b/c of prolonged APD and QT interval--> Torsades de Pointes
When are Quinidine and Procanamide contraindicated?
Patients with a hx of:
-Torsades De Pointes
- Long QT
- Heart block
- Sinus node dysfunction
What are the extra-cardiac adverse effects of Procainamide?
1) SLE-like syndrome
2) Nausea and vomiting
3) Decreased kidney function
What are the Class Ib antiarrhythmics?
What is the general mechanism of action of the Class Ib antiarrhythmics?
1) Weak binding to Na+ channels-->small impact on Phase 0 depolarization
2) Acceleration of phase 3 repolarization with little effect on ADP or QT interval
What is the mechanism of action of Lidocaine?
1) Blocks open and inactivated Na+ channels, reducing Vmax of Phase 0
2) Shortens cardiac action potential (in cases where the AP has been long) by binding to SLOW Na+ channels and Ca++ channels
3) Lower the slope of phase 4, increasing the threshold for excitation
What can cause a prolonged cardiac action potential?
This is caused by a slow inactivation of Na+ channels, which are blocked by Lidocaine.
What are the clinical indications for Lidocaine?
Previously first line for ventricular tachycardia but now SECONDARY to amiodarone
Is Lidocaine effective for prophylaxis of arrhythmias secondary to MI?
What are the key pharmacologic points to remember about Lidocaine?
1) Extensive 1st pass metabolism necessitates IV administration
2) Requires a multiple loading doses and maintenance infusions
What are the adverse effects associated with Lidocaine administration?
1) Rapid bolus can cause tinnitus and seizure
2) High doses induce CNS depression
Why should care be taken when giving Lidocaine to HF patients?
Decreased clearance and increased plasma concentrations could lead to adverse effects
List the Class Ic antiarrhythmics?
What is the general mechanism of action of the Class Ic antiarrhythmics?
- Strong binding to Na+ channels (most potent), which will:
1) Increase APD, QRS, and PR interval
What is the specific mechanism of action of Propafenone?
1) Strong inhibitor of Na+ channel
2) B-adrenergic antagonism
Why does Propafenone have some Beta effects?
Similar structure to propranolol
What are the clinical indications for Propafenone?
1) Atrial arrhythmia
3) Ventricular arrhythmia in patients with NO HEART DISEASE
What is the specific mechanism of action of Flecainide?
This is a potent Na+ channel blocker which,
- Decreased Phase 0
- Marked slowing of intraventricular conduction to increase the QRS duration
What are clinical indications for Flecainide?
Refractory ectopic ventricular arrhythmias
What is the general mechanism of action of the Class II antiarrhythmics?
What are the physiologic effects of Class II antiarrhythmics?
- Decreased SA nodal automaticity
- Decreased conduction through the AV node
- Decreased ventricular contractility
What are Class II antiarrhythmics effective for treating?
1) SVT due to excessive sympathetic activity
2) ONLY drugs effective in preventing sudden cardiac death s/p MI
What are Class II antiarrhythmics ineffective at treating?
Severe arrhythmias such as recurrent VT
What is the general mechanism of action of the Class III antiarrhythmics?
1) Block K+, Ca++, Na+, and B-receptors
2) MAIN effect is K+, which prolongs phase 3 repolarization, increasing the QT interval
What is the specific mechanism of action of Amiodarone?
Class III i.e. blocks:
1) K+ channels which prolongs refractriness and APD
2) Na+ channels in the inactivated state
3) Ca++ channels to slow phase 4 in nodal cells
What are the indications for Amiodarone?
1) Acute termination of VT or VF (replacing lidocaine)
2) Conversion of a-fib
Why is Amiodarone replacing Lidocaine out-of-hospital?
B/c of its multiple receptor effects and ability to prevent numerous types of arrhythmias
Why are there multiple adverse effects associated with Amiodarone?
1) Highly lipophilic
2) Multiple receptor effects
3) Extremely long half-life