Download Antiarrhythmic Drugs

Antiarrhythmic Drugs
Antiarrhythmic Drug Classes
Arrhythmias
1. Class 1 – Sodium Channel Blockers
(Singh-Vaughn-Williams Classifications)
Abnormalities in the heart’s
1. Impulse Formation (abnormal automaticity)
a. Slow rate – bradycardia
b. Fast rate – tachycardia
c. Irregular rate – extrasystole/fibrillation
2. Impulse Conduction
a. Blockade
b. Reentry
3. All cardiovascular diseases are associated with at least on type
of arrhythmias
Types of Cardiac Arrhythmias
1. Supraventricular Arrhythmias (above the ventricles)
a. Supraventricular extrasystole
b. Supraventricular tachycardia
c. Atrial flutter
d. Atrial fibrillation
2. Ventricular Arrhythmias
a. Ventricular extrasystoles
b. Ventricular tachycardia
c. Ventricular fibrillation
3. Blockages
a. SA block
b. AV block
c. Right bundle block
d. Left bundle block
a.
i.
ii.
b.
i.
c.
i.
ii.
Class 1A
Quinidine
Procainamide
Class 1B
Lidocaine
Class 1C
Flecainide
Propafenone
2. Class 2 – Beta Blocker
a. Propanolol
b. Esmolol
c. Metoprolol
3. Class 3 – Potassium Channel Blocker
a. Amiodarone
b. Ibutilide
4. Class 4 – Calcium Channel Blocker
a.
i.
b.
i.
Phenylalkylamine
Verapamil
Benzothiazepine
Diltiazem
5. Miscellaneous groups
a.
b.
c.
d.
e.
Digoxin - atrial fibrillation
Adenosin – supraventricular tachycardia
Magnesium sulphate – Torsades de Pointes
Potassium – digoxin intoxification
Atropine – AV blockade/ Bradycardia
Arrhythmogenic Effects
The ability of antiarrhythmic agents to cause other type of arrhythmias
1. The most common drug-induce arrhythmias are
a. Ventricular tachycardia
b. Torsades de Pointes
i. Polymorphic ventricular tachycardia
ii. Due to prolonged QT interval
2. ALL antiarrhythmic agents can cause
arrhythmogenic effects!!
3. The most potent arrhythmogenics drugs are
a. Class IC – Flecainide/Propanefone
b. Class III – Amiodarone
Dangerous antiarrhythmic drug combinations
1. Class II (Propanolol) + Class IV (Verapamil/Diltiazem)
a. Sinus and AV node depression
i. Bradycardia
ii. AV blockade
iii. Risk of asystole
b. Marked negative inotropic effects
2. Class IA (Quinidine/Procainamide) + Class IC (Flecainide/Propanefone)
a. Highly potent arrhythmogenic effects
i. ↑↑↑risk of ventricular tachycardia
3. Class IC (Flecainide/Propanefone) + Class III (Amiodarone/Ibutilide)
a. Massive prolongation of QT interval
b. ↑↑↑ risk of Torsades de Pointes
Classes
Drugs
Mechanism
of action
Therapeutic
Uses
Side Effects
Additional
Informations
Class 1A
Quinidine
Procainamide
Class 1B
Lidocaine
1. Blocks Na+ channels
a. Prevents Na+ influx
b. Slows depolarization (phase 0)
c. Widens QRS complex
2. Blocks K+ channels
a. Prolongs repolarization
b. Prolongs Effective Refractory Period (ERF)
c. Prolongs QT interval
i. ↑risk of Torsades de Pointes
3. Blocks Alpha receptors
a. Vasodilatory effects
1. Low effect on blocking Na+ channels
a. Does not change the QRS
complex
2. ↑K+ conduction
a. Shortens repolarization
b. ↓ERF
c. ↓QT interval
3. No effect on cardiac contractility
1. Supraventricular arrhythmias
2. Ventricular arrhythmias
3. Antimalarial – Quinidine
Quinidine
ii. Headache
iii. Vertigo
1. Cinchonism,
iv. Blurred vision
characterized by
2. Hypotension
a. GIT disturbances
3. Hypersensitivity
i. Vomitting
a. Rashes
ii. Diarrhea
b. Fever
iii. Nausea
c. Angioedema
b. CNS disturbances
i. Tinnitus
Quinidine
1. Given orally
2. Contraindication
a. Acute heart failure
i. ↓cardiac contractility
3. Drug drug interaction
a. Highly plasma protein binding; may displace
i. Digoxin
ii. Warfarin
b. Extensively metabolized by hepatic CYP450
system
i. Given with CYP450 inducer ↓efficacy
ii. Given with CYP450 inhibitor ↑toxicity
1. Ventricular arrhythmias ONLY
2. Myocardial infarction
3. Heart failure
1. CNS disturbances
a. Tinnitus
b. Seizures
c. Drowsiness
1. Also been used as local anaesthetics
2. Never been given though oral route
a. Due to massive undergoing 1st pass
metabolism
Class 1C
Flecainide
Propafenone
1. The most potent Na+ channels
blocker
a. Significantly slows
depolarization
b. Significantly widens QRS
complex
2. Does not have any activity on
K+ channels
a. No effect on repolarization
b. Does not change QT interval
and ERF
3. Some degree of beta receptors
blockage
1. Supraventricular arrhythmias
2. Ventricular arrhythmias
1. Highly arrhythmogenics
Drug Name/Infos
1. Propanolol
2. Esmolol
3. Metoprolol
Contraindications
1. Asthma
2. COPD
3. Heart block
4. Peripheral
vascular diseases
Class II Antiarrhythmic Drug (Beta Adrenergic Blocking Agents)
Mechanism of Action
Therapeutic Uses
1. Blocking the Beta receptor especially Beta 1
receptors on the heart will inhibit the
stimulation of sympathetic of the heart
2. Blocking the beta receptors will block the
activity of Adenylate Cyclase
3. Inhibition of Adenylate Cyclase will reduce
the level of intracellular cAMP which in turn
reducing the activation of Protein Kinase
4. Reduced in the activation of Protein Kinase
will inhibit further biochemical cascade in
the heart cells which leads to
a. Negative Chronotropic
i. Slows sinus rhythm (RR interval)
b. Negative Dromotropic
i. Slows AV conduction
ii. Prolong PR interval
c. No effect on repolarization
i. Does not change QT interval
d. Negative Inotropic
1. Supraventricular
arrhythmias
2. Ventricular arrhythmias
3. Myocardiac infarction
4. Chronic heart failure
5. Angina pectoris
*Safe to be given as
prophylaxis in arrhythmias
Adverse Effects
1. AV block
2. Bronchoconstriction
3. Masked hypoglyceamia in
insulin dependent diabetic
patients
4. Bradycardia
Drugs
Mechanism
of action
Therapeutic
Uses
Class III Antiarrhythmic Drug (Potassium Channel Blocker)
Ibutilide
Amiodarone
1. Pure potassium channel blocker
2. Blockade of potassium channel leads to
a. Prolongs repolarization
b. Prolongs ERF
c. Prolongs QT interval
3. No effects on Na+ channels
a. Does not effect depolarization
b. Does not change QRS complex
The most potent antiarrhythmic agents
1. Blocks Na+ channels
a. Prolongs depolarization
b. Widens QRS complex
2. Blocks Beta adrenegic receptors
a. Negative chronotropic
b. Negative dromotropic
c. Negative inotropic
3. Blocks K+ channels
a. Prolongs repolarization
b. Prolongs QT interval
i. Highly susceptible to cause Torsades de Pointes
c. Prolongs ERF
4. Blocks Ca2+ channels
a. Prolongs plateau phase
b. Prolongs PR interval
1. Supraventricular arrhythmias
2. Ventricular arrhythmias (life threatening)
a. Ventricular fibrillation
b. Ventricular tachycardia
1. Headache
2. Irregular heart beat
1. Supraventricular arrhythmias
2. Ventricular arrhythmias
Side Effects
Additional
Informations
1. Should only be given through IV
a. Undergoes extensive 1st pass effect
2. Undergoes hepatic CYP450 metabolism
a. Given with CYP450 inducer will ↓ efficacy
b. Given with CYP450 inhibitor will ↑toxicity
1.
2.
3.
4.
5.
1.
2.
3.
4.
Pulmonary fibrosis
Impaired thyroid function (due to its similarities to iodine in structure)
a. Hyperthyroidism
b. Hypothyroidism
Blue-grey discoloration of skin
Impaired liver function
Corneal micro-deposit
Can be given through
a. Oral route
b. IV route
Has a very long half life – 58 days
a. It needs loading dose in order to reach rapid plasma therapeutic
level
Tends to accumulate in the tissues
It is extensively metabolized in the liver
5. Acts as CYP450 inhibitor
a.
i.
ii.
iii.
iv.
Increase the toxic level of
Warfarin
Simvastatin
Phenytoin
Digoxin
Drug Name/Infos
Pheylalkylamine
o Verapamil
 Benzothiazepine
o Diltiazem

Contraindication
1. Acute heart
failure
a. Due to marked
↓ in cardiac
contractility
Class IV Antiarrhythmic Drug (Calcium Channel Blockers)
Mechanism of Action
Therapeutic Uses
Ca2+
1. Blocks L type
channels
a. Located at
i. SA node
ii. AV node
b. Leads to
i. Prolong sinus rhythm (RR interval)
ii. Prolong PR interval
2. Does not have any effect on
a. QRS complex
b. QT interval
1. Supraventricular
arrhythmias ONLY
Adverse Effects
1. Hypotension
2. Headache
3. Edema