Quinidine

• Overview

  • dextroisomer of quinine; quinidine gluconate (Quinaglute, Quinalan) also has antimalarial and antipyretic effects

• Pharmacokinetics:

  • 80%-90%: bound to plasma albumin

  • Rapid oral absorption; rapid attainment of peak blood levels (60-90 minutes)

  • Elimination half-life: 5-12 hours

  • IM injection, possible but not recommended due to injection site discomfort

  • IV administration: limited due to myocardial depression & peripheral vasodilation

• Metabolism:

  • Hepatic: hydroxylation to inactive metabolites; followed by renal excretion

  • 20% excreted unchanged in urine

    • Impaired hepatic/renal function: accumulation of quinidine and metabolites

  • Sensitive to enzyme induction by other agents--

    • decreased quinidine blood levels with phenytoin, phenobarbital, rifampin

• Mechanism of antiarrhythmic action-- primarily activated sodium channel blockade which results in:

  • Depression of ectopic pacemaker activity

  • Depression of conduction velocity

    • may convert a one-way conduction blockade to a two-way (bidirectional) block -- terminating reentry arrhythmias

  • Depression of excitability (particularly in partially depolarized tissue)

  • Recovery from sodium channel blockade is slower in depolarized tissue (compared to normal tissue):

    • This is the basis for relative selectivity of quinidine action in depolarized tissue compared to normal tissue, (i.e. lengthened refractory period, depressed conduction velocity, reduced excitability observed in depolarized tissue to greater extent the normal tissue)

  • Although classified as a sodium channel blocker, quinidine also blocks K+ channels.

    • Most antiarrhythmic agents have such multiple actions.

• Effect on the ECG: QT interval lengthening

  • Basis: quinidine-mediated reduction in repolarizing outward potassium current

    • Result:

      • Longer action potential duration

      • Increased effective refractory period

      • Reduces reentry frequency; reduced rate in tachyarrhythmias

• Sodium channel blockade results in

  • an increased threshold

  • decreased automaticity.

• Quinidine Uses

  • Used to manage nearly every form of arrhythmia especially acute and chronic supraventricular dysrhythmias

  • Ventricular tachycardia

  • Frequent indications:

  • Prevent recurrence of supraventricular tachyarrhythmias

  • Suppression ventricular premature contractions

  • Approximately 20% of patients with atrial fibrillation will convert to normal sinus rhythm following quinidine treatment

  • Supraventricular tachyarrhythmia due to Wolff-Parkinson-White syndrome -- effective suppression by quinidine

  • Digitalization prior to quinidine administration:

  • Quinidine sulfate (Quinidex,Quinora)/quinidine gluconate (Quinaglute, Quinalan) may cause a paradoxical increase in ventricular response due to quinidine's vagolytic effect at the AV node (antimuscarinic action increases AV nodal throughput, allowing more SA nodal impulses to reach the ventricle)

  • Vagotonic effects on digitalis prevents this paradoxical increase by increasing vagal tone at AV node

  • Quinidine sulfate (Quinidex,Quinora) administration results in vagal inhibition (anti-muscarinic) and alpha-adrenergic receptor blockade.

• Quinidine Side Effects

  • Cardiovascular--at (high) plasma concentrations (> 2ug/ml)

    • Prolongation (ECG) of PR interval, QRS complex, QT interval

    • Heart block likely with 50% increase in QRS complex duration (reduced dosage)

      • Quinidine syncope: may be caused by delayed intraventricular conduction, resulting in ventricular dysrhythmia

      • Patients with preexisting QT interval prolongation or evidence of existing A-V block (ECG): probably should not be treated with quinidine

    • Hypotension -- primarily following IV administration

      • Mechanism: peripheral vasodilation secondary to alpha-adrenergic receptor blockade

      • Increased hypotension risk associated with quinidine +verapamil treatment

    • Effects on heart rate:

      • increase secondary to either quinidine's antimuscarinic effect and/or reflex increase in sympathetic activity

    • Quinidine is associated with Torsades de pointes, a ventricular arrhythmias associated with marked QT prolongation.

• Torsades de pointes: Electrophysiological Features

  • ventricular origin

  • wide QRS complexes with multiple morphologies

  • changing R - R intervals

  • axis seems to twist about the isoelectric line

  • This potentially serious arrhythmia occurs in 2% - 8% if patients, even if they have a therapeutic or subtherapeutic quinidine blood level.

• Other quinidine adverse effects include:

  • cinchonism

    • blurred vision, decreased hearing acuity, gastrointestinal upset,headaches and tinnitus.

  • Nausea, vomiting, diarrhea (30% frequency)

• Drug-drug interaction:quinidine gluconate (Quinaglute, Quinalan)-digoxin (Lanoxin, Lanoxicaps)

  • Quinidine increases digoxin plasma concentration; may cause digitalis toxicity in patients taking digoxin or digitoxin

• Effects on neuromuscular transmission:

  • Quinidine gluconate (Quinaglute, Quinalan) interferes with normal neuromuscular transmission; enhancing the effect of neuromuscular-blocking drugs

  • Recurrence of skeletal muscle paralysis postoperatively may be associated with quinidine administration

Category: Pharmacology Notes