EXAM #1: CV PHARM 2 Flashcards by muhammad bin amjad

What are the three consequences of arrhythmia?

1) Compromise of mechanical performance
2) Arrhythmogenesis/ evolution
3) Thrombogenesis

Note that decreased mechanical performance of the LV leads to a direct decrease in SV and CO.

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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

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What is the maximum diastolic potential?

The absolute value of the repolarization–deepening (called increase) this will DECREASE spontaneous activity

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What does increasing the action potential duration do to the ERP/ADP ratio?

Decreases the ERP/ADP ratio–>arrhythmothgenic

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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

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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

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Why do K+ channel blockers increase the action potential duration?

Decrease phase 3 re-polarization b/c of less K+ efflux

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What is the general mechanism of action of the Class I antiarrhythmics?

Blockade of fast inward Na+ channels in conductive tissues of the heart

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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

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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

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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

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What are the Class Ia antiarrhythmics?

Quinidine
Procainamide
Disopyramide

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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

Secondarily, Quinidine

Block K+ channels–>increasing QT interval
Blocks M receptors–>increasing HR
Alpha antagonist–>decrease BP

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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

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What are the adverse effects of Quinidine?

1) Cinchonism (tinnitus)
2) Thrombocytopenia
3) Torsades de Pointes
4) Nausea
5) Hypotension

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What is cinchonism?

This is a triad of symptoms seen from quidine overdose or its natural source, cinchona bark, including:

Tinnitus
Hearing-loss
Blurred vision

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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

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What are the physiologic effects of Procainamide?

Decreased conduction, automaticity, and excitability

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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

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What are the clinical indications for Procainamide?

1) Life-threatening ventricular arrhythmias
2) Re-entrant SVT
3) A-fib
4) A-flutter with WPW

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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
Hypokalemia
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?

Lidocaine Phenytoin Mexiletin Tocainide

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?

- Ischemia - MI - Digitalis 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?

Propafenone Flecainide Morizicine

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 2) PSVT 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?

Beta-adrenergic antagonists

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 3) AVNRT 4) WPW

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

What are the adverse effects associated with Amiodarone?

1) Until tissue/myocardium concentrations are equilibrated, redistribution OUT of the myocardium can cause early RECURRENCE of arrhythmia 2) Decreased contractility leading to hypotension (in high doses > 5mg) 3) LETHAL interstitial pneumonitis 4) Hyperthyroidism OR hypothyroidism