Antiarrhythmics- Austin and his student

What adrenergic receptor controls the heart?

b1

T/F The atria and ventricles contract independently of each other.

T

What is the missing step in the following conduction pathway?

1. SA nodes serves as pacemaker

2. atria contract

3. signal _________________

4. conduction then spreads rapidly/uniformly

5. ventricular contraction

signal delayed at AV node

Answer the following about electrolyte channels and cardiac APs:

T/F: All muscle cells in the body contain a plateau phase in their AP.

F- cardiac myocytes ONLY MUSCLE W/ plateau

What node is the most important for normal heart rate control?

SA node

SA node is influenced primarily by the slope of phase ___ depolarization.

4

How does sympathetic activation effect heart rate, threshold potential, action potentials, and depolarization?

• Heart rate= INCREASE

• Threshold potential= DECREASE

• Action potential duration= SHORTER

• Depolarization= FASTER

Arrhythmias may be caused by…

• anatomical defects

• electrolyte imbalances

• ischemia

• stress

• caffeine, smoking, decongestants

What are the symptoms of arrhythmias?

• Dyspnea (SOB)

• Dizziness

• Fatigue

• Syncope

• Angina

• Palpitations

What is the difference between a tachyarrhythmia and a bradyarrhythmia?

tachyarrhythmia- increased firing rate (>100 bpm)

bradyarrhythmia- decreased firing rate (<60 bpm)

Be familiar with this chart

Example Q using the chart:

If I had acute supraventricular tachycardia, the arrhythmia would stem from the _____________.

a. atria

b. SA node

c. AV node

d. ventricle

c

What is the importance of the QT interval?

represents ventricular depolarization

• fastest way to die

Above what QTc level would cardiac arrest or a lethal arrhythmia like Torsades de pointes occur?

a. QTc > 510 mS

b. QTc >470 mS

c. QTc >450 mS

d. QTc >525 mS

a. QTc > 510 mS

What classes of drugs can cause a prolonged QT interval?

• antipsychotics

• antidepressants

• antibacterials

• antiarrhythmics

What 3 things can you use to treat arrhythmias?

• Implantable cardioverter defibrillators (ICD)

  • used in high death risk

  • constant monitor for v-fib and v-tach

• Catheter ablation

  • catheter heat destroys abnormal tissue

• Drugs

The Vaughn-Williams classification system is used for antiarrhythmic drugs. Fill in the following table:

What drugs belong to class II antiarrhythmics?

b-blockers

B-blockers inhibit phase ___ depolarization.

4

What structure of the heart do beta-blockers effect?

SA and AV nodes

What arrhythmias are b-blockers particularly useful for?

• exercise-induced arrhythmias

• stress-induced arrhythmias

• post-MI arrhythmias

Common ADRs of Class II antiarrhythmics/ b-blockers:

• bradycardia

• hypotension

• bronchospasm in non-selective bb’s

• heart block

• insomnia, depression

Can Class II and Class IV antiarrhythmics be combined to treat arrhythmias?

• For example, can I combine diltiazem and metoprolol?

NO!

• increases risk of HF= too much shutdown

Which class of antiarrhythmics inhibits sympathetic input to pacing regions of the heart?

II

Which class of antiarrhythmics block open calcium channels to slow conduction in tissues dependent on Ca²⁺ current?

IV

What structure of the heart do non-DHP CCBs effect?

SA and AV nodes

What are the ADRs of Class IV antiarrhythmics aka non-DHPs?

• AV nodal block

• HA, fatigue, dizzy

• nausea, constipation

Which of the following is true regarding Class II and Class IV antiarrhythmics?

SATA

a. both effect the SA and AV nodes

b. both decrease CO

c. dangerous if used together

d. both decrease the slope of phase 0 depolarization

a, b, c

• d is false- only Class IV decreases the slope of phase 0 depolarization

What drugs belong to class Ia antiarrhythmics?

• Disopyramide

• Quinidine

• Procainamide

What drugs belong to class Ib antiarrhythmics?

• Lidocaine

• Mexiletine

• Phenytoin (Ochs has this one on hers so i just added it here)

What drugs belong to class Ic antiarrhythmics?

• Flecainide

• Propafenone

What drugs belong to class III antiarrhythmics?

• Amiodarone

• Dronedarone

• Dofetilide

• Ibutalide

• Sotalol

Class I antiarrhythmics effect phase ___ of the cardiac action potential.

0

Which classes are effective for supraventricular AND ventricular arrhythmias?

SATA

a. Class Ia

b. Class Ib

c. Class Ic

a, c

Which classes are effective ONLY for ventricular arrhythmias?

SATA

a. Class Ia

b. Class Ib

c. Class Ic

b

Which Class I subgroup has MODERATE Na+ channel blockage?

Ia

Which Class I subgroup has WEAK Na+ channel blockage?

Ib

Which Class I subgroup has STRONG Na+ channel blockage?

Ic

What is the main ADR of the class Ia antiarrhythmic Disopyramide?

anticholinergic side effects

What are the contraindications for each class Ia antiarrhythmic?

• disopyramide

• quinidine

• procainamide

IN ALL: 2nd/3rd heart block

• disopyramide- cardiogenic shock, QT prolongation

• quinidine- thrombocytopenia, myasthenia gravis

• procainamide- systemic lupus erythematous, torsade de pointes

Which class Ia agent is an IV injection not an oral capsule?

Procainamide

When is lidocaine, a class Ib agent, used?

IV injection used for refractory ventricular tachycardia and cardiac arrest

What are the contraindications of Class Ib agents?

• Lidocaine

• Mexiletine

BOTH: 2nd/3rd degree heart block

• Lidocaine- Wolff-Parkinson-White syndrome, corn allergy, amide-allergy

• Mexiletine- cardio shock,

What is a warning with Mexiletine?

Severe skin reactions (DRESS)

What class I agent has some beta blocker activity?

propafenone

Flecainide should be avoided in what?

chronic a-fib

Class IC agents are contraindicated in what?

• HF

• MI

Class III antiarrhythmics block K+ channels at phase ___ of the cardiac action potential.

3

What class III antiarrhythmics are ONLY effective for supraventricular arrhythmias?

• dronedarone

• ibutilide

• dofetilide

What class III antiarrhythmics are effective for BOTH supraventricular and ventricular arrhythmias?

• amiodarone

• sotalol

What element does amiodarone contain that could potentially cause thyroid problems?

iodine

Amiodarone and Dofetilide are the drugs of choice with what comorbidity?

HF

What are the BBW for amiodarone?

• pulmonary toxicity

• hepatotoxicity

• proarrhythmic affects

In addition to the the BBW for amiodarone, what are some of the other warnings?

• thyroid dysfunction

• visual impairment

• photosensitivity

• neuropathy

When starting amiodarone what do we do to digoxin?

decrease dose by 50%

When starting amiodarone what do we do to warfarin?

decrease warfarin dose by 30-50%

Amiodarone is inhibitors of what CYP enzymes?

• CYP2C9

• CYP2D6

• Pgp

What are the boxed warnings of Dronedarone?

• a-fib: increased risk of death, stroke, HF

• HF: increased risk of death

What are the contraindications of Dronedarone?

• permanent a-fib

• HF

• QTC >500

• bradycardia

• use of CYP3A4 inhibitors

Although Sotalol is a class III agent, it has some class ___ activity since it’s a nonselective beta-blocker.

II

Ibutilide is an IV formulation only indicated for what?

cardioversion to normal sinus rhythm

What must be corrected before beginning Ibutilide?

hypokalemia and hypomagnesemia

Dofetilide must be initiated with continuous monitoring for ____ hours.

72

Dofetilide is contraindicated in…

QTc>440

CrCl <20

Initiation of which drugs must be done under observation?

dofetilide and sotalol

Does Digoxin deal with rate or rhythm control?

RATE

What does digoxin block?

Na-K-ATPase Pump

How do Digoxin and Adenosine effect the heart?

slow conduction through AV node