Quinidine

It is one of the alkaloids of cinchona also known as beta-quinine (it is an a C-9 epimer of quinine). Quinidine is also referred to as conquinine. It is the most primitive form of class IA drug.

Mechanism of action:
Its most important effect is on Phase 0 of the action potential causing a decrease in rapid depolarization by blocking the sodium channels.

It affects Phase 4 also when there is slow depolarization by slow opening of sodium channels.

Actions:
It causes the inhibition of ventricular arrhythmias, reentry arrhythmia and arrhythmias originating from other than normal place.

Cardiac effects:

High concentration of Quinidine directly affects the cardiac cells whereas low concentrations of Quinidine causes indirect (anti-cholinergic) effects on the heart.

Quinidine decreases ectopic pacemaker rate, conduction velocity (negative dromotropism) and excitability especially in depolarized tissue. By decreasing conduction velocity (negatively dromotropic) it causes a promoted effective refractory period in atrial, ventricular and Purkinje fibers.

It increases duration of action potential which along with promoted effective refractory period decreases maximum reentry frequency.
Quinidine has α-adrenoceptor blocking properties which causes vasodilation and a reflex increase in SA nodal rate.

Other effects:
It has

1. antimalarial,
2. antipyretic and
3. oxytocic properties, so that increasing the contractions of the muscles of the womb during childbirth.

Pharmacokinetics:
Quinidine sulfate is well absorbed orally. It is metabolized in the liver by cytochrome p450 enzyme and excreted through the kidneys.

Therapeutic uses:
It is used for

1. Atrial, AV junctional and ventricular tachyarrhythmias
2. Premature atrial and ventricular contractions
3. It has the ability of maintaining sinus rhythm after sudden outburst of atrial fibrillations and flutter
4. Interatrial and atrioventricular nodal reentrant arrhythmias
5. Wolf Parkinson white tachycardia

Adverse effects:
Cinchonism (characterized by headache, tinnitus, photophobia, confusion), Anorexia, Gastrointestinal intolerance (Nausea), Rashes, Hepatitis

It may cause worsening of arrhythmia. It may block SA or AV nodes.