Mechanism Of Action
LidaMantle® Cream and LidaMantle® Lotion release lidocaine which stabilizes
the neuronal membrane by inhibiting the ionic fluxes required for initiation
and conduction of impulses, thereby effecting local anesthetic action. AcidMantle
vehicle lowers pH to increase protection against alkaline irritants and to provide
a favorable environment for healing.
Lidocaine may be absorbed following topical administration to mucous membranes,
its rate and extent of absorption depending upon the specific site of application,
duration of exposure, concentration, and total dosage. In general, the rate
of absorption of local anesthetic agents following topical application occurs
most rapidly after intratracheal administration. Lidocaine is also well-absorbed
from the gastrointestinal tract, but little intact drug appears in the circulation
because of biotransformation in the liver.
Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged
drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation,
ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation,
a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide
and glycinexylidide. The pharmacological/toxicological actions of these metabolites
are similar to, but less potent than, those of lidocaine. Approximately 90%
of lidocaine administered is excreted in the form of various metabolites, and
less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate
of 4-hydroxy-2, 6-dimethylaniline.
The plasma binding of lidocaine is dependent on drug concentration, and the
fraction bound decreases with increasing concentration. At concentrations of
1 to 4 g of free base per mL, 60 to 80 percent of lidocaine is protein bound.
Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
Lidocaine crosses the blood-brain and placental barriers, presumably by passive
Studies of lidocaine metabolism following intravenous bolus injections have
shown that the elimination half-life of this agent is typically 1.5 to 2 hours.
Because of the rapid rate at which lidocaine is metabolized, any condition that
affects liver function may alter lidocaine kinetics. The half-life may be prolonged
two-fold or more in patients with liver dysfunction. Renal dysfunction does
not affect lidocaine kinetics but may increase the accumulation of metabolites.
Factors such as acidosis and the use of CNS stimulants and depressants affect
the CNS levels of lidocaine required to produce overt systemic effects. Objective
adverse manifestations become increasingly apparent with increasing venous plasma
levels above 6 g free base per mL. In the rhesus monkey arterial blood levels
of 18-21 g/mL have been shown to be threshold for convulsive activity.