Propranolol

It is helpful in myocardial ischemia. It decreases mortality rate by reducing ventricular arrhythmia.

Mechanism of action:
It acts on both β1 and β2 adrenoceptors i.e. cause their blockage.

Actions:

It has both negative inotropic and chronotropic effect resulting in the decrease of cardiac output.
It also decreases SA and AV nodal activity.
It shows promising effects in angina by decreasing cardiac output, work load on the heart and oxygen consumption of the heart muscles at rest and in physical activity.

In the first instance, it produces anti-hypertensive effects by reduced cardiac output associated with bradycardia. And its long term use inhibits renin secretion, which results in reduced peripheral resistance leading to anti-hypertensive effects.


Due to β2-blockade, it causes an elevated airway resistance.

It causes an increased sodium retention.

Antiarrhythmic action:

Its effects are due to β-adrenoceptor blockade but also due to a direct membrane effect. It

1. Suppresses SA nodal firing
2. Reduces automaticity in purkinje fibers
3. A substantial promotion in effective refractory period of AV node

Therapeutic uses:

1. Chronic form of angina pectoris
2. prophylaxis of myocardial infarction and migraine
3. Hypertension
4. Hyperthyroidism

Antiarrhythmic uses:
It is used for:

1. Atrial flutter or fibrillation
2. Sudden outburst of supraventricular tachycardia
3. Ventricular arrhythmias due to:
    a. increased adrenergic activation
    b. Toxicity caused by digitalis

Adverse effects:
Sedation, depression, cardiac failure, nausea, vomiting, bronchconstriction, diarrhea, rashes, fever, impaired metabolism (Due to reduced glycogenolysis and glucagon secretion caused by β-blockade)

Class II Antiarrhythmic Drugs

Class II drugs are β-adrenergic receptor antagonists.

Action:
These agents have the ability of decreasing Phase 4 depolarization thus suppresses the automaticity, causing a prolonged AV conduction and decreased cardiac rate and contractility.

Therapeutic uses:
Class II drugs are used in the treatment of tachycardia due to promoted activity of sympathetic system.

They are also useful in the treatment of atrial flutter and fibrillation.

They are used in AV nodal re-entrant tachycardia.

Propafenone

Same as that of flecainide. It has the ability of allowing conduction in all the tissues of heart.

Flecainide

It binds to sodium channels and slowly detaches from sodium channels.

Mechanism of action:
It is a sodium channel blocker. It suppresses phase 0 of action potential in purkinje fibers and fibers of the muscles of the heart.

Actions:
It does not affect greatly the action potential.

1. In this case, automaticity of the ectopic pacemaker is decreased by the promoted threshold potential (not by a reduction in the slope of phase 4 depolarization).
2. It causes a decreased conduction and excitability and promoted refractory period (pronounced in the depolarized tissue).

Pharmacokinetics:
It is absorbed orally and it has a half life of about 16-20 hours.

Therapeutic uses:
1. It is used in premature ventricular contractions, refractory ventricular tachycardia and supraventricular tachycardia.
2. It is used for the inhibition of sudden outburst of atrial fibrillation or flutter.

Adverse effects:
It may cause dizziness, blurred vision, anorexia, nausea, vomiting, impotence and in some cases may worsen preexisting arrhythmias.

Mexiletine and tocainide

These are almost similar to lidocaine. But they can be administered orally.
Therapeutic uses:
They are used for ventricular arrhythmias.

Adverse effects:
Tocainide may cause pulmonary toxicity which may cause pulmonary fibrosis.

Phenytoin

Antiarrhythmic action


Its effects are almost same to that of lidocaine
1. It depresses unprovoked automaticity in atrial and ventricular tissues although it does no affect on intraventricular conduction.
2. It causes a promoted conduction through impaired purkinje fibers.
3. It is especially useful for ventricular arrhythmias related to digitalis toxicity or myocardial ischemia.

Lidocaine

It is a local anesthetic containing amide in structure.

Mechanism of action:
They act fast on sodium channels and also get detached from sodium channels rapidly. It shortens Phase 3 repolarization and blocks sodium channels and has the ability of shortening the duration of action potential.

Actions:
Due to short duration of action potential it prolongs diastole. On the other hand, it decreases the effective refractory period of purkinje fibers.

Therapeutic uses:
It is used for ventricular arrhythmias during open heart surgery, digitalis toxicity and myocardial ischemia.

It is used as local anesthesia.

Pharmacokinetics:
It undergoes first pass metabolism by the liver, so that is why it is given intravenously. In the liver, the drug is dealkalyted and approximately the entire drug is excreted by the liver.

Adverse effects:
It may cause paresthesias, hypotension, tremor, drowsiness, convulsions and respiratory arrest.

Administration and Dosage:
It is given IV with a loading dose of 150-200 mg in 15 minutes succeeded by maintenance dose of 2-4 mg/min.