Lidocaine

• Overview/Pharmacokinetics:

  • Local anesthetic administered by i.v. for therapy of ventricular arrhythmias

  • Extensive first-pass effect requires IV administration

  • Half-life: two hours

  • Infusion rate: should be adjusted based on lidocaine plasma levels

  • Factors influencing loading and maintenance doses:

    • Congestive heart failure (decreasing volume of distribution and total body clearance)

    • Liver disease: plasma clearance -- reduced; volume of distribution -- increased; elimination half-life substantially increased (3 X or more)

    • Drugs that decrease liver blood flow (e.g. cimetadine, propranolol), decreased lidocaine clearance (increased possible toxicity)

• Metabolism

  • Hepatic;some active metabolites

• Cardiovascular Effects:

  • Site of Action: Sodium Channels

    • Blocks activated and inactivated sodium channels (quinidine blocks sodium channels only in the activated state)

    • During diastole, in normal tissue, as membrane potential returns to normal resting levels (-90 mV) lidocaine rapidly dissociates from the channel (low affinity for the channel resting state)

    • During diastole, in ischemic tissue, the membrane potential does not return to normal resting levels but remains partially depolarized and lidocaine remains bound (higher affinity, longer time constant for unblocking that at less negative resting potentials)

    • Therefore, lidocaine is more effective in suppressing activity in depolarized, arrhythmogenic cardiac tissue but has little effect on normal cardiac tissue -- the basis for this drug's selectivity.

      • Very effective antiarrhythmic agent for arrhythmia suppression associated with depolarization (e.g., digitalis toxicity or ischemia)

      • Comparatively ineffective in treating arrhythmias occurring in normally polarized issue (e.g., atrial fibrillation or atrial flutter)

    • No significant effect on QRS or QT interval or on AV conduction (normal doses)

    • Lidocaine (Xylocaine) decreases automaticity by reducing the phase 4 slope and by increasing threshold.

  • Clinical Uses:

    • Suppression of ventricular arrhythmias (limited effect on supraventricular tachyarrhythmias)

    • Suppression of reentry-type rhythm disorders:

      • premature ventricular contractions (PVCs)

      • ventricular tachycardia

    • May reduce incidence of ventricular fibrillation during the initial time frame following acute myocardial infarction; no evidence to support prophylactic use and myocardial infarction

  • Side Effect/Toxicities

    • Overdosage:

      • vasodilation

      • direct cardiac depression

      • decreased cardiac conduction -- bradycardia; prolonged PR interval; widening QRS on ECG

    • Major side effect -- neurological

      • Large doses, rapidly administered can result in seizure.

        • Factors that reduce seizure threshold for lidocaine:

          • hypoxemia, hyperkalemia, acidosis

      • Otherwise: CNS depression, apnea.

Category: Pharmacology Notes