Lesson 12.2. Class I Anti-Arrythmitic Drugs

Class I

All members slow conduction in ischemic and depolarized cells and slow or abolish abnormal pacemakers wherever these processes depend on Na-channels

Class IB

most selective with significant effects on Na-channels in depressed ischemic tissue (tissues that lack oxygen supply) but not on channels in normal cells

Class IA and IC

less selective but produces significant reduction of Ina in depressed tissues and less blockade in normal cells

open or inactivated

Na-channel blocker binds to receptors rapidly when the channel is a._________ and less readily when b.___________________

a = ?

resting or full repolarized

Na-channel blocker binds to receptors rapidly when the channel is a._________ and less readily when b.___________________

b = ?

Proarrhythmic

Most Class I drugs are a._______________ drugs and are b.______________ blockers.

a = ?

Sodium Channel

Most Class I drugs are a._______________ drugs and are b.______________ blockers.

b = ?

upstroke

Class IA

1. Prolongs _____________ by blocking Na-channel

2. Prolongs _____________ because it will take longer before relax and contract, has time to recuperate or send out signals

1 = ?

action potential

Class IA

1. Prolongs _____________ by blocking Na-channel

2. Prolongs _____________ because it will take longer before relax and contract, has time to recuperate or send out signals

2 = ?

all arrhythmias

Class IA are used for _________________________.

Proarrhythmic

SIDE EFFECTS OF CLASS IA:

1. anti-arrhythmic side effect; can also cause arrhythmia, needs to be monitored

2. side effect associated with Procainamide

3. other side effect

1 = ?

Lupus-like

SIDE EFFECTS OF CLASS IA:

1. anti-arrhythmic side effect; can also cause arrhythmia, needs to be monitored

2. side effect associated with Procainamide

3. other side effect

2 = ?

Hyperkalemia

SIDE EFFECTS OF CLASS IA:

1. anti-arrhythmic side effect; can also cause arrhythmia, needs to be monitored

2. side effect associated with Procainamide

3. other side effect

3 = ?

Sodium Lactate

TOXICITIES OF CLASS IA:

1. add more sodium because of blockage

2. high blood pressure for patients

1 = ?

Pressor Sympathetics

TOXICITIES OF CLASS IA:

1. add more sodium because of blockage

2. high blood pressure for patients

2 = ?

Procainamide

CLASS IA:

• prototype

AP and conduction

CLASS IA:

Procainamide — Cardiac Effects

1. Slows the upstroke of ___________________

2. Prolongs ___________________ of the ECG.

3. Prolong APD (Class III activity) by non-specific K-channel blockade.

4. _____________________________________________, counterbalanced by drug-induced vagal block.

1 = ?

QRS duration

CLASS IA:

Procainamide — Cardiac Effects

1. Slows the upstroke of ___________________

2. Prolongs ___________________ of the ECG.

3. Prolong APD (Class III activity) by non-specific K-channel blockade.

4. _____________________________________________, counterbalanced by drug-induced vagal block.

2 = ?

APD

CLASS IA:

Procainamide — Cardiac Effects

1. Slows the upstroke of ___________________

2. Prolongs ___________________ of the ECG.

3. Prolong APD (Class III activity) by non-specific K-channel blockade.

4. _____________________________________________, counterbalanced by drug-induced vagal block.

3 = ?

Direct depressant action on SA and AV nodes

CLASS IA:

Procainamide — Cardiac Effects

1. Slows the upstroke of ___________________

2. Prolongs ___________________ of the ECG.

3. Prolong APD (Class III activity) by non-specific K-channel blockade.

4. _____________________________________________, counterbalanced by drug-induced vagal block.

4 = ?

ganglion-blocking

CLASS IA:

Procainamide — Extra-Cardiac Effects

• It has a.______________ properties which reduces b.____ and may cause c._________________ due to rapid infusion of Procainamide.

a = ?

PVR

CLASS IA:

Procainamide — Extra-Cardiac Effects

• It has a.______________ properties which reduces b.____ and may cause c._________________ due to rapid infusion of Procainamide.

b = ?

hypotension

CLASS IA:

Procainamide — Extra-Cardiac Effects

• It has a.______________ properties which reduces b.____ and may cause c._________________ due to rapid infusion of Procainamide.

c = ?

action potential

CLASS IA:

Procainamide — Toxicity

1. Excessive prolongation of ___________________

2. Excessive _______________ prolongation

3. Induction of ______________________________ due to active metabolite NAPA

4. Long-term therapy may result in ______________ symptoms due to active metabolite NAPA

1 = ?

QT interval

CLASS IA:

Procainamide — Toxicity

1. Excessive prolongation of ___________________

2. Excessive _______________ prolongation

3. Induction of ______________________________ due to active metabolite NAPA

4. Long-term therapy may result in ______________ symptoms due to active metabolite NAPA

2 = ?

Torsades de Pointes and other arrhythmia

CLASS IA:

Procainamide — Toxicity

1. Excessive prolongation of ___________________

2. Excessive _______________ prolongation

3. Induction of ______________________________ due to active metabolite NAPA

4. Long-term therapy may result in ______________ symptoms due to active metabolite NAPA

3 = ?

Lupus-related

CLASS IA:

Procainamide — Toxicity

1. Excessive prolongation of ___________________

2. Excessive _______________ prolongation

3. Induction of ______________________________ due to active metabolite NAPA

4. Long-term therapy may result in ______________ symptoms due to active metabolite NAPA

4 = ?

IV, IM, and oral

CLASS IA:

Procainamide — PK and Dosage

1. Administered _________________

2. Produces an active metabolite ________ with Class 3 activity

3. Dose reduction for patients with __________ due to accumulation of NAPA to avoid heart failure.

4. T1/2 (half-life) of procainamide is ___________

5. _______________________________________ due to NAPA

1 = ?

NAPA

CLASS IA:

Procainamide — PK and Dosage

1. Administered _________________

2. Produces an active metabolite ________ with Class 3 activity

3. Dose reduction for patients with __________ due to accumulation of NAPA to avoid heart failure.

4. T1/2 (half-life) of procainamide is ___________

5. _______________________________________ due to NAPA

2 = ?

renal failure

CLASS IA:

Procainamide — PK and Dosage

1. Administered _________________

2. Produces an active metabolite ________ with Class 3 activity

3. Dose reduction for patients with __________ due to accumulation of NAPA to avoid heart failure.

4. T1/2 (half-life) of procainamide is ___________

5. _______________________________________ due to NAPA

3 = ?

3-4 hrs

CLASS IA:

Procainamide — PK and Dosage

1. Administered _________________

2. Produces an active metabolite ________ with Class 3 activity

3. Dose reduction for patients with __________ due to accumulation of NAPA to avoid heart failure.

4. T1/2 (half-life) of procainamide is ___________

5. _______________________________________ due to NAPA

4 = ?

longer DOA and accumulates slowly

CLASS IA:

Procainamide — PK and Dosage

1. Administered _________________

2. Produces an active metabolite ________ with Class 3 activity

3. Dose reduction for patients with __________ due to accumulation of NAPA to avoid heart failure.

4. T1/2 (half-life) of procainamide is ___________

5. _______________________________________ due to NAPA

5 = ?

atrial and ventricular arrhythmias

CLASS IA:

Procainamide — Therapeutic Use

1. For all types of arrhythmias (mostly for _________________________).

2. It is the 2nd/3rd choice (after lidocaine or amiodarone) for _______________________________________.

1 = ?

sustained ventricular arrhythmia associated with acute myocardial infarction

CLASS IA:

Procainamide — Therapeutic Use

1. For all types of arrhythmias (mostly for _________________________).

2. It is the 2nd/3rd choice (after lidocaine or amiodarone) for _______________________________________.

2 = ?

Quinidine

CLASS IA:

• from alkaloids

AP and conduction

CLASS IA:

Quinidine — Cardiac Effects

1. Slows the upstroke of ________________________

2. Prolongs ______ duration of the ECG

3. Prolong ___ (Class Ill activity) by blockade of several K-channels including Ito

1 = ?

QRS

CLASS IA:

Quinidine — Cardiac Effects

1. Slows the upstroke of ________________________

2. Prolongs ______ duration of the ECG

3. Prolong ___ (Class Ill activity) by blockade of several K-channels including Ito

2 = ?

APD

CLASS IA:

Quinidine — Cardiac Effects

1. Slows the upstroke of ________________________

2. Prolongs ______ duration of the ECG

3. Prolong ___ (Class Ill activity) by blockade of several K-channels including Ito

3 = ?

diarrhea, nausea, and vomiting

CLASS IA:

Quinidine — Extra-cardiac Effects

1. It can cause Gl effects: ____________________________.

2. At toxic concentrations, it can cause _____________________________.

3. Idiosyncratic / Immunologic reactions like _________________________.

1 = ?

cinchonism, a syndrome of headache, dizziness, and tinnitus

CLASS IA:

Quinidine — Extra-cardiac Effects

1. It can cause Gl effects: ____________________________.

2. At toxic concentrations, it can cause _____________________________.

3. Idiosyncratic / Immunologic reactions like _________________________.

2 = ?

thrombocytopenia, hepatitis, angioneurotic edema, and fever

CLASS IA:

Quinidine — Extra-cardiac Effects

1. It can cause Gl effects: ____________________________.

2. At toxic concentrations, it can cause _____________________________.

3. Idiosyncratic / Immunologic reactions like _________________________.

3 = ?

action potential

CLASS IA:

Quinidine — Toxicity

1. Excessive prolongation of __________________

2. Excessive ___ interval prolongation.

3. Induction of _____________________ and other arrhythmia.

4. Excessive _______________ blockade

5. Modest __________________________ on the heart.

1 = ?

QT

CLASS IA:

Quinidine — Toxicity

1. Excessive prolongation of __________________

2. Excessive ___ interval prolongation.

3. Induction of _____________________ and other arrhythmia.

4. Excessive _______________ blockade

5. Modest __________________________ on the heart.

2 = ?

Torsades de Pointes

CLASS IA:

Quinidine — Toxicity

1. Excessive prolongation of __________________

2. Excessive ___ interval prolongation.

3. Induction of _____________________ and other arrhythmia.

4. Excessive _______________ blockade

5. Modest __________________________ on the heart.

3 = ?

Na-channel

CLASS IA:

Quinidine — Toxicity

1. Excessive prolongation of __________________

2. Excessive ___ interval prolongation.

3. Induction of _____________________ and other arrhythmia.

4. Excessive _______________ blockade

5. Modest __________________________ on the heart.

4 = ?

anti-muscarinic action

CLASS IA:

Quinidine — Toxicity

1. Excessive prolongation of __________________

2. Excessive ___ interval prolongation.

3. Induction of _____________________ and other arrhythmia.

4. Excessive _______________ blockade

5. Modest __________________________ on the heart.

5 = ?

GIT

CLASS IA:

Quinidine — PK and Dosage

1. Readily absorbed in the ______

2. Metabolized in the _______

3. It is rarely used because of the __________________________________ and availability of a better option

1 = ?

liver

CLASS IA:

Quinidine — PK and Dosage

1. Readily absorbed in the ______

2. Metabolized in the _______

3. It is rarely used because of the __________________________________ and availability of a better option

2 = ?

cardiac and extra-cardiac ADRs

CLASS IA:

Quinidine — PK and Dosage

1. Readily absorbed in the ______

2. Metabolized in the _______

3. It is rarely used because of the __________________________________ and availability of a better option

3 = ?

Brugada syndrome

CLASS IA:

Quinidine — Therapeutic Use

1. Beneficial for the management of _________________ (rare inherited heart problem, fast pumping of ventricles)

2. For patients that can undergo _________________________________

1 = ?

implantation of implantable cardioverter defibrillators (ICD)

CLASS IA:

Quinidine — Therapeutic Use

1. Beneficial for the management of _________________ (rare inherited heart problem, fast pumping of ventricles)

2. For patients that can undergo _________________________________

2 = ?

AP and conduction

CLASS IA:

Disopyramide —Cardiac Effect

1. Slows the upstroke of __________________

2. Prolongs ____ duration of the ECG

3. Prolong APD (Class Ill activity) by blockade of several K-channels including Ito

1 = ?

QRS

CLASS IA:

Disopyramide —Cardiac Effect

1. Slows the upstroke of __________________

2. Prolongs ____ duration of the ECG

3. Prolong APD (Class Ill activity) by blockade of several K-channels including Ito

2 = ?

APD

CLASS IA:

Disopyramide — Cardiac Effect

1. Slows the upstroke of __________________

2. Prolongs ____ duration of the ECG

3. Prolong APD (Class Ill activity) by blockade of several K-channels including Ito

3 = ?

action potential

CLASS IA:

Disopyramide — Toxicity

1. Excessive prolongation of ______________

2. Excessive ___ interval prolongation

3. It has a a.___________ effect - may lead to b.______________ or those with c.___________________.

4. ___________________ - dry mouth, blurred vision, constipation, and worsening of glaucoma.

1 = ?

QT

CLASS IA:

Disopyramide — Toxicity

1. Excessive prolongation of ______________

2. Excessive ___ interval prolongation

3. It has a a.___________ effect - may lead to b.______________ or those with c.___________________.

4. ___________________ - dry mouth, blurred vision, constipation, and worsening of glaucoma.

2 = ?

negative inotropic

CLASS IA:

Disopyramide — Toxicity

1. Excessive prolongation of ______________

2. Excessive ___ interval prolongation

3. It has a a.___________ effect - may lead to b.______________ or those with c.___________________.

4. ___________________ - dry mouth, blurred vision, constipation, and worsening of glaucoma.

3.a. = ?

heart failure de novo

CLASS IA:

Disopyramide — Toxicity

1. Excessive prolongation of ______________

2. Excessive ___ interval prolongation

3. It has a a.___________ effect - may lead to b.______________ or those with c.___________________.

4. ___________________ - dry mouth, blurred vision, constipation, and worsening of glaucoma.

3.b. = ?

left ventricular depression

CLASS IA:

Disopyramide — Toxicity

1. Excessive prolongation of ______________

2. Excessive ___ interval prolongation

3. It has a a.___________ effect - may lead to b.______________ or those with c.___________________.

4. ___________________ - dry mouth, blurred vision, constipation, and worsening of glaucoma.

3.c. = ?

Atropine-like activity

CLASS IA:

Disopyramide — Toxicity

1. Excessive prolongation of ______________

2. Excessive ___ interval prolongation

3. It has a a.___________ effect - may lead to b.______________ or those with c.___________________.

4. ___________________ - dry mouth, blurred vision, constipation, and worsening of glaucoma.

4 = ?

oral drug

CLASS IA:

Disopyramide — PK and Dosage

1. Available only as an ___________.

2. Dose adjustment is recommended for patients with _________________.

1 = ?

renal impairment

CLASS IA:

Disopyramide — PK and Dosage

1. Available only as an ___________.

2. Dose adjustment is recommended for patients with _________________.

2 = ?

supraventricular arrhythmias

CLASS IA:

Disopyramide — Therapeutic Use

• It has useful effects for a.___________________ BUT is only approved for b._________________________.

a = ?

ventricular arrhythmia

CLASS IA:

Disopyramide — Therapeutic Use

• It has useful effects for a.___________________ BUT is only approved for b._________________________.

b = ?

ischemic cells

Class IB is selective to _____________ which are those that no longer receives or has an imbalance with oxygen (can't receive oxygenated blood)

atrial/normal cells

Class IB has little to no effect on ___________________

shorten

Class IB _______ the action potential.

phase 0

Class IB does not occur in __________.

Lidociane

Class IB

• prototype

activated & inactivated Na-channel

CLASS IB:

Lidocaine — Cardiac Effect

1. Blocks _______________________________ with rapid kinetics.

2. In depolarized cells, increased inactivation and slow unbinding kinetics results in _________________ of conduction.

1 = ?

selective depression

CLASS IB:

Lidocaine — Cardiac Effect

1. Blocks _______________________________ with rapid kinetics.

2. In depolarized cells, increased inactivation and slow unbinding kinetics results in _________________ of conduction.

2 = ?

least cardiotoxic

CLASS IB:

Lidocaine — Toxicity

1. One of the __________________ Class I anti-arrhythmic drugs.

2. Proarrhythmic effects (uncommon)

3. For patients with a history of heart failure, lidocaine may cause ____________.

4. Most common ADRs (more common among elderly, or with rapid administration)

1 = ?

SA node arrest, worsening of impaired conduction, and ventricular arrhythmia

CLASS IB:

Lidocaine — Toxicity

1. One of the __________________ Class I anti-arrhythmic drugs.

2. Proarrhythmic effects (uncommon)

3. For patients with a history of heart failure, lidocaine may cause ____________.

4. Most common ADRs (more common among elderly, or with rapid administration)

2 = ?

hypotension

CLASS IB:

Lidocaine — Toxicity

1. One of the __________________ Class I anti-arrhythmic drugs.

2. Proarrhythmic effects (uncommon)

3. For patients with a history of heart failure, lidocaine may cause ____________.

4. Most common ADRs (more common among elderly, or with rapid administration)

3 = ?

paresthesias, tremor, nausea, lightheadedness, hearing disturbances, slurred speech, and convulsions

CLASS IB:

Lidocaine — Toxicity

1. One of the __________________ Class I anti-arrhythmic drugs.

2. Proarrhythmic effects (uncommon)

3. For patients with a history of heart failure, lidocaine may cause ____________.

4. Most common ADRs (more common among elderly, or with rapid administration)

4 = ?

IV drug

CLASS IB:

Lidocaine — PK and Dosage

1. For arrhythmia, administered only as ____ because of extensive first-pass effect.

2. Higher dosing for patients with a.____________ due to increased levels of b.__________________.

1 = ?

MI or other acute illness

CLASS IB:

Lidocaine — PK and Dosage

1. For arrhythmia, administered only as ____ because of extensive first-pass effect.

2. Higher dosing for patients with a.____________ due to increased levels of b.__________________.

2.a. = ?

α1-acid glycoprotein

CLASS IB:

Lidocaine — PK and Dosage

1. For arrhythmia, administered only as ____ because of extensive first-pass effect.

2. Higher dosing for patients with a.____________ due to increased levels of b.__________________.

2.b. = ?

ventricular tachycardia

CLASS IB:

Lidocaine — Therapeutic Use

1. It is the agent of choice for a._____________________ and prevention of b.___________________ after cardioversion in the setting of acute ischemia.

2. It is also used as a ________________________

1.a. = ?

ventricular fibrillation

CLASS IB:

Lidocaine — Therapeutic Use

1. It is the agent of choice for a._____________________ and prevention of b.___________________ after cardioversion in the setting of acute ischemia.

2. It is also used as a ________________________

1.b. = ?

local anesthetic

CLASS IB:

Lidocaine — Therapeutic Use

1. It is the agent of choice for a._____________________ and prevention of b.___________________ after cardioversion in the setting of acute ischemia.

2. It is also used as a ________________________

2 = ?

Mexiletine

CLASS IB:

• Orally active congener of lidocaine with very similar electrophysiologic and anti-arrhythmic actions

ventricular arrhythmias

CLASS IB:

• Mexiletine is primarily used for _____________________

neurologic

CLASS IB:

• Dose-related ADRs of Mexiletine is mostly a.________ even at therapeutic dosage such as b.____________________________.

a = ?

tremors, blurred vision, nausea and lethargy

CLASS IB:

• Dose-related ADRs of Mexiletine is mostly a.________ even at therapeutic dosage such as b.____________________________.

b = ?

chronic pain due to diabetic neuropathy or nerve injury

CLASS IB:

• Mexiletine has beneficial effects in relieving _______________________ (off-label used at 450-750 mg/d)

Phenytoin

used for digoxin toxicity and reverse digitalis-induced arrhythmia

upstroke

CLASS IC:

Flecainide

1. Prolongs ____________

2. Doesn't affect the duration of _____________

3. ______________ effect

1 = ?

action potential

CLASS IC:

Flecainide

1. Prolongs ____________

2. Doesn't affect the duration of _____________

3. ______________ effect

2 = ?

Proarrhythmic

CLASS IC:

Flecainide

1. Prolongs ____________

2. Doesn't affect the duration of _____________

3. ______________ effect

3 = ?

Na+ and K+ channel

CLASS IC:

Flecainide

• potent a.___________________ blocker (without prolongation of b.____ interval) with slow c.__________________

a = ?

AP or QT

CLASS IC:

Flecainide

• potent a.___________________ blocker (without prolongation of b.____ interval) with slow c.__________________

b = ?

unblocking kinetics

CLASS IC:

Flecainide

• potent a.___________________ blocker (without prolongation of b.____ interval) with slow c.__________________

c = ?

supraventricular arrhythmia

CLASS IC:

Flecainide Uses:

1. normal heart patients with ___________________________

2. very effective in suppressing __________________________

1 = ?

premature ventricular contractions

CLASS IC:

Flecainide Uses:

1. normal heart patients with ___________________________

2. very effective in suppressing __________________________

2 = ?

ventricular tachyarrhythmia, myocardial infarction and ventricular ectopy

CLASS IC:

Flecainide Proarrhythmic effects

• severe exacerbation of arrhythmia among patients with pre-existing ____________________________________________________

Propafenone

CLASS IC:

• Structurally similar to propranolol → weak 𝛽-blocking action

Quinidine (IA)

CLASS IC:

Propefanone

• Spectrum of action is very similar to a._______________ but does not prolong b.______________; similar c._____________ with Flecainide (IC)

a = ?

action potential

CLASS IC:

Propefanone

• Spectrum of action is very similar to a._______________ but does not prolong b.______________; similar c._____________ with Flecainide (IC)

b = ?

Na-channel blocking kinetics

CLASS IC:

Propefanone

• Spectrum of action is very similar to a._______________ but does not prolong b.______________; similar c._____________ with Flecainide (IC)

c = ?