Drugs Used in Cardiac Arrhythmias

Question 1

Class 1 Sodium Channel-blocking Drugs: 1A

Answer 1

– Quinidine (Cardioquin)
– Procainamide (Pronestyl)
– Disopyramide (Norpace)

Question 2

Class 1 Sodium Channel-blocking Drugs: 1B

Answer 2

– Lidocaine (Xylocaine)

– Mexiletine (Mexitil)

Question 3

Class 1 Sodium Channel-blocking Drugs: 1C

Answer 3

– Flecainide (Tambocor)

– Propafenone (Rythmol)

Question 4

Class 2 Beta Blockers

Answer 4

– Esmolol (Brevibloc)

– Propranolol (Inderal)

Question 5

Class 3 Potassium Channel-blocking Drugs

Answer 5

– Amiodarone (Cordarone)
– Sotalol (Betapace)
– Dofetilide (Tikosyn)
– Ibutilide (Corvert)

Question 6

Class 4 Cardioactive Calcium Channel Blockers

Answer 6

– Verapamil (Isoptin)

– Diltiazem (Cardizem)

Question 7

Miscellaneous agents

Answer 7

Adenosine (Adenocard)

Question 8

Fast action potential in cardiac muscle: Which phase?

• Voltage-dependent fast Na+ channels open as a result of depolarization; Na+ enters the cells down its electrochemical gradient

Answer 8

Phase 0

Question 9

Fast action potential in cardiac muscle: Which phase?

• K+ exits cells down its gradient, while fast Na+ channels close, resulting in some repolarization

Answer 9

Phase 1

Question 10

Fast action potential in cardiac muscle: Which phase?

• plateau phase results from K+ exiting cells offset by and Ca2+ entering through slow voltage-
  dependent Ca2+ channels

Answer 10

Phase 2

Question 11

Fast action potential in cardiac muscle: Which phase?

• Ca2+ channels close and K+ begins to exit more rapidly resulting in repolarization

Answer 11

Phase 3

Question 12

Fast action potential in cardiac muscle: Which phase?

• Resting membrane potential is gradually restored by Na+/K+ ATPase and the Na+/Ca2+
  exchanger

Answer 12

Phase 4

Question 13

Effects of Class 1A drugs

Answer 13

• Block sodium channels
• Bind to open (ACTIVATED) sodium channels
• Dissociate from channel with INTERMEDIATE kinetics
• Block POTASSIUM channels
• PROLONG AP duration **
• Prolong QRS and QT intervals of the ECG **

Question 14

Class 1A: Procainamide

Clinical Use?

Answer 14

• Used infrequently (frequent dosing is required,
common occurrence of lupus-related side effects)

• Is effective in sustained VENTRICULAR TACHYCARDIAS and arrhythmias associated with myocardial infarction (not
a first choice drug for these indications)

• Sidenote: it directly depresses the activities of SA and AV nodes

Question 15

Class 1A: Procainamide

Adverse effects?

Answer 15

• Cardiac
– QT interval prolongation
– Induction of torsade de pointes
arrhythmias and syncope 
– Excessive inhibition of conduction

• Extracardiac
– Lupus erythematosus syndrome with arthritis, pleuritis, pulmonary disease, hepatitis and fever
– Nausea, diarrhea
– Agranulocytosis

Question 16

Class 1A: Quinidine

Pharmacodynamics and clinical use?

Answer 16

– Affords antimuscarinic effect on the heart –> may ENHANCE AV conductance

– Exhibits beta-blocking activity (effect on PR interval is
variable)

– May cause HYPOTENSION –> tachycardia

Question 17

Class 1A: Quinidine

Clinical use?

Answer 17

Rarely used because of cardiac and extracardiac adverse

effects and the availability of better-tolerated antiarrhythmic drugs

Question 18

Class 1A: Quinidine

Adverse effects?

Answer 18

• Cardiac:
– QT interval prolongation
– Induction of torsade de pointes arrhythmia and
syncope
– Excessive slowing of conduction throughout the
heart

• Extracardiac:
– GI side effects (diarrhea, nausea, vomiting)
– Headache, dizziness, tinnitus (cinchonism)
– Thrombocytopenia, hepatitis, fever

Question 19

Class 1A: Disopyramide

Clinical use?

Answer 19

Recurrent ventricular arrhythmias

Question 20

Class 1A: Disopyramide

Adverse effects?

Answer 20

• Cardiac: QT interval prolongation, induction of torsade de pointes arrhythmia and syncope, negative inotropic effect – may precipitate heart failure, excessive depression of cardiac conduction

• Extracardaic: atropine-like symptoms – urinary
retention, dry mouth, blurred vision, constipation, exacerbation of glaucoma

Question 21

Effect of Class 1B Drugs

Answer 21

• Block sodium channels
• Bind to INACTIVATED sodium channels (bind to depolarized cells)
• Dissociate from channel with fast kinetics
• SHORTEN the AP
• Do NOT block potassium channels
• Do NOT prolong AP or QT duration

Question 22

Class 1B: Lidocaine

Clinical use?

Answer 22

Termination of ventricular tachycardia in the setting

of acute myocardial ischemia

Question 23

Class 1B: Lidocaine

Adverse effects?

Answer 23

• The least toxic of all Class 1 drugs

• Cardiovascular: may cause HYPOTENSION in patients
with heart failure by inhibiting cardiac contractility, proarrhythmic effects are uncommon

• Neurological effects: paresthesias, tremor, slurred
speech, convulsions

Question 24

Class 1B: Mexiletine

Clinical use?

Answer 24

• Ventricular arrhythmias

• To relieve chronic pain, especially pain due to
diabetic neuropathy and nerve injury

Question 25

Class 1B: Mexiletine Adverse effects?

Answer 25

* Tremor * Blurred vision * Nausea * Lethargy

Question 26

Effect of Class 1C Drugs

Answer 26

- Block sodium channels - Bind to open (ACTIVATED) sodium channels - Dissociate from channel with SLOW kinetics - Block certain potassium channels ** - Do NOT prolong AP duration and QT interval duration of the ECG ** - Prolong QRS interval duration **

Question 27

Class 1C : Flecainide What channels does it block?

Answer 27

Blocks sodium and potassium channels

Question 28

Class 1C : Flecainide Clinical use?

Answer 28

In patients with otherwise normal hearts who have | supraventricular arrhythmias

Question 29

Class 1C : Flecainide Adverse effects?

Answer 29

• May be very effective in suppressing premature ventricular contractions, but may cause severe exacerbation of ventricular arrhythmias when administered to – Patients with preexisting ventricular tachyarrhythmias – Patients with a previous myocardial infarction – Patients with ventricular ectopic rhythms

Question 30

Class 1C : Propafenone Clinical use?

Answer 30

Supraventricular arrhythmias in patients without structural disease

Question 31

Class 1C : Propafenone Adverse effects?

Answer 31

* Exacerbation of ventricular arrhythmias * A metallic taste * Constipation

Question 32

Class 2 Beta-Blockers Effect on AP?

Answer 32

• Slow action potential – Sinoatrial node – decrease HR (increase RR interval) – AV node – decrease AV conductance (increase PR interval)

Question 33

Class 2 Beta-Blockers: Clinical use of propranolol in cardiac arrhythmias?

Answer 33

* Arrhythmias associated with stress and THYROID storm * Atrial fibrillation and flutter * Paroxysmal supraventricular arrhythmias • Arrhythmias associated with MI – Decrease mortality in patients with MI

Question 34

Class 2 Beta-Blockers: Esmolol Clinical use?

Answer 34

* Supraventricular arrhythmias * Arrhythmias associated with thyrotoxicosis • Myocardial ischemia or acute myocardial infarction with arrhythmias • As an adjunct drug in general anesthesia to control arrhythmias in perioperative period

Question 35

Adverse effects of Beta-blockers?

Answer 35

``` – Reduced cardiac output – Bronchoconstriction – Impaired liver glucose mobilization – Produce an unfavorable blood lipoprotein profile (increase VLDL and decrease HDL) – Sedation, depression – Withdrawal syndrome associated with sympathetic hyperresponsiveness ```

Question 36

Contraindications to Beta-blockers?

Answer 36

``` – Asthma – Peripheral vascular disease – Raynaud’s syndrome – Type 1 diabetics on insulin – Bradyarrhythmias and AV conduction abnormalities – Severe depression of cardiac function ```

Question 37

Class 3 Potassium Channel Blockers: Effects of Class 3 drugs?

Answer 37

– Block potassium channels – Prolong action potential duration – Prolong QT interval on ECG – Prolong refractory period

Question 38

Class 3 Potassium Channel Blockers: Amiodarone Clinical use?

Answer 38

* Recurrent ventricular tachycardia | * Atrial fibrillation

Question 39

Class 3 Potassium Channel Blockers: Amiodarone Effects on heart rate and conduction?

Answer 39

- Has calcium channel blocking activities - Causes bradycardia and slows AV conduction - Causes peripheral vasodilation (effect may be related to the action of the vehicle)

Question 40

Class 3 Potassium Channel Blockers: Amiodarone Adverse effects?

Answer 40

• Cardiac - AV block and bradycardia - Incidence of torsade de pointes is low as compared to other Class 3 drugs • Extracardiac - Fatal pulmonary fibrosis - Hepatitis - Photodermatitis, deposits in the skin, gives blue-grey skin discoloration in sun-exposed areas - Deposits of drug in cornea and other eye tissues, optical neuritis - Blocks the peripheral conversion of thyroxine to triiodothyronine, also a source of inorganic iodine in the body – may cause HYPO- OR HYPERTHYROIDISM

Question 41

Class 3 Potassium Channel Blockers: Sotalol Clinical use?

Answer 41

• Treatment of life-threatening ventricular arrhythmias • Maintenance of sinus rhythm in patients with atrial fibrillation

Question 42

Class 3 Potassium Channel Blockers: Sotalol Adverse effects?

Answer 42

* Depression of cardiac function | * Provokes torsade de pointes

Question 43

Class 3 Potassium Channel Blockers: Dofetilide Clinical use?

Answer 43

• Restore sinus rhythm in patients with atrial fibrillation • Maintain the sinus rhythm after cardioversion in patients with atrial fibrillation

Question 44

Class 3 Potassium Channel Blockers: Dofetilide Adverse effects?

Answer 44

QT interval prolongation and increased risk of | ventricular arrhythmias

Question 45

Class 3 Potassium Channel Blockers: Ibutilide Clinical use?

Answer 45

Conversion of atrial flutter and atrial fibrillation to sinus rhythm

Question 46

Class 3 Potassium Channel Blockers: Ibutilide Adverse effects?

Answer 46

QT interval prolongation and increased risk of ventricular arrhythmias (patients require continuous ECG monitoring until QTc returns to baseline)

Question 47

Effect of Class 4 L-type calcium channel blockers

Answer 47

• Block both ACTIVATED AND INACTIVATED L-type calcium channels • Active in slow response cells - Decrease the slope of phase 0 depolarization - Increase L-type Ca2+ channel threshold potential - Prolong refractory period in AV node • Slow sinoatrial node depolarization, cause bradycardia • Prolong action potential duration and conduction time in AV node

Question 48

Effect of Class 4 L-type calcium channel blockers: Clinical use?

Answer 48

* Termination and prevention of paroxysmal supraventricular tachycardia * Ventricular rate control in atrial fibrillation and flutter

Question 49

Effect of Class 4 L-type calcium channel blockers: Adverse effects?

Answer 49

``` • Cardiac – Negative inotropy – AV block – Sinoatrial node arrest – Bradyarrhythmias – Hypotension ``` • Extracardiac – Constipation (Verapamil)

Question 50

Miscellaneous: Adenosine Effects of Adenosine

Answer 50

– Activates potassium current and inhibits Ca2+ and Funny currents, causing marked hyperpolarization and suppression of action potentials in slow cells – Inhibits AV conduction and increases nodal refractory period

Question 51

Miscellaneous: Adenosine Clinical use?

Answer 51

Conversion to sinus rhythm in paroxysmal supraventricular tachycardia

Question 52

Miscellaneous: Adenosine Adverse effects?

Answer 52

• Shortness of breath • Bronchoconstriction (both A1 and A2B adenosine receptors cause bronchoconstriction) * Chest burning * AV block * Hypotension