Drugs

Question 1

What is Mexiletine´s mechanism of action?

Answer 1

Class Ib antiarrhythmic.
It blocks fast sodium channels, reducing phase 0 maximal upstroke velocity of the action potential.

Question 2

What is the classification of antiarrhythmic drugs and their main mechanism of action?

Answer 2

Class I: Sodium channel blockers - decrease speed of depolarization (slowing conduction)
Class II: Beta-blocking agents - decrease sympathetic tone, affect mainly SA and AV node
Class III: Potassium channel blockers - increase action potential duration (prolonging refractoriness) - amiodarone, sotalol, dronedarone
Class IV: Calcium channel blockers - affecting mainly SA and AV node - verapamil, dialtiazem, amlodipine, nifidepine
Class V: Digitalis agents - affect mainly SA and AV node indirectly by increasing vagal tone

Question 3

What is the subclassification of the Class I AAD?

Answer 3

Class Ia: decrease conductivity, increases/ prolongs refractoriness, widenes QRS duration - quinidine, procainamide, disopyramide Side-effects: Prolongs QT interval - risk ot TdP, GI upset
Class Ib: decrease the duration of the action potential; shortens the refractory period - mexiletine, lidocaine Side-effects: negatively inotropic, dizziness, numbness or tingling of extremeties
Class Ic: decrease conduction velocity of the action potential; has little or no effect on refractory period) - flecainide, propafenone, encainide Side-effects: increases risk of SCD for patients with LV dysfunction and structural heart disease

Flecainide can increase the pacing thtreshold

Question 4

What is the mechanism of action of Amiodarone?

Answer 4

Increases AP duration and refractory period. It is a Class III AAD - potassium channel blocker.
QT prolongation
Good for atrial and ventricular arrhythmias
Safe in heart failure
Long oral loading and half life

Side-effects: Photosensitivity
Pulmonary fibrosis
Ophtalmic - optic neuritis, corneal deposit
Hepatitis
Hyper/Hypothyroidism

Question 5

What is the mechanism of action of Sotalol? What is it´s AAD class?

Answer 5

Sotalol has beta-blocker and class III effects. Doses >80 mg bd for class III effects

Question 6

What are the main heart failure drugs?

Answer 6

ACE-I (Angiotensin converting enzyme inhibitors): prevents converting of inactive angiotensin I to powerful vasoconstrictor angiotensin II. Enalapril, Captopril, Lisinopril.
**B-blockers **
Dapagliflozin
Entresto
MRA (Mineralocorticoid receptor antagonists / aldosterone antagonist): potassium sparing diuretic (weak diuretic). Competitive antagonist of aldosterone. Spironalactone, Eplerenone.
ARB (Angiotensin II receptor blocker): Losartan, Valsartan, Candesartan, Telmisartan
Diuretics: Furosemide, Bumetanide, Indapamide, Hydroclorothyazide, Spironalactone, Eplerenone

Question 7

What are the main ICD and antiarrhythmic drugs interactions?

Answer 7

*Sodium channel blockers (class I AAD) increase the DFT or the energy for successful defibrillation.
*Potassium channel blockers (Class III AAD) decrease DFTs.
*Antiarrhythmic drugs may affect pacing threshold, making it more difficult to capture.
*Antiarrhythmic drugs substantially slow the conduction of the action potential, thereby prolonging the QRS in the electrogram with the possibility of double counting and inappropriate shocks (especially Na-channel blocking drugs)

Question 8

Name AA drug therapy that increases the DFT

Answer 8

Quinidine
Disopyramide
Procainamide
Lidocaine
Mexilitine
Flecanaide
Propanolol
Amiodarone
Verapamil
Diltiazem

Question 9

Name AA drugs that decrease DFT (Potassium channel blockers - Class III)

Answer 9

Sotalol
Dofetilide

Question 10

Name AA drugs that have variable effect on DFT

Answer 10

Propafenone
Bretylium

Question 11

Name the most common AADs

Answer 11

Class I: Sodium channel blockers
1a: Quinidine, Procainamide, Disopyramide
1b: Lidocaine, Mexiletine
1c: Flecainide, Propafenone

Class II: Beta-blockers
Propanolol, Metoprolol

Class III: Potassium channel blockers
Sotalol, Dofetilide, Amiodarone (increases DFT despite being a Class III AAD), Azimilide

Class IV: Calcium channel blockers
Verapamil, Diltiazem

Question 12

What factors/drugs that increase pacing threshold?

Answer 12

eating (hyperglycemia) - high vagal tone
hypoxemia (decrease O2 in blood) - acidosis
Acute viral illness
electrolyte fluctuations (Hyperkalemia - Increased potassium (normal 3.6-5.2)
Quinidine (Class IA drug)
Procainamide (Class Class 1A)
Beta-blocker (Class II) - Sotalol, Carvedilol, Metoprolol, Propanolol)
Verapamil (Class IV)
Amiodarone (Class III)
Flecainide (Class 1C)

Question 13

What factors/drugs decrease pacing threshold?

Answer 13

Sleep
Digitalis
Atropine
Epinephrine
Isoprenaline
Corticosteroids