Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1     Pharmacodynamic properties

Pharmacotherapeutic group: local anaesthetics: amides, ATC code: N01BB52.

As other local anaesthetics, lidocaine reversibly blocks the propagation of the impulse along the nerve fibers, thus preventing the mobility of sodium ions through the nerve membrane.

At high doses lidocaine has a quinidine-like action on the myocardium, i.e., cardiac depressant. All local anaesthetics stimulate the central nervous system and may produce anxiety, restlessness and tremors.

The onset and duration of lidocaine action are increased by adding epinephrine as vasoconstrictor.
Thus, the absorption of the anaesthetic is delayed and a greater concentration is obtained for a longer period. Also, the possibility of systemic adverse effects is reduced.

Pharmacokinetic Properties

5.2     Pharmacokinetic properties

Absorption
The information obtained from different formulations, concentrations and uses shows that lidocaine is absorbed completely upon parenteral administration and that its absorb ration depends, for example, on various factors such as the site of administration and the presence or absence of a vasoconstrictor. Except for intravascular administration, the highest blood concentrations are obtained via intercostal nerve blockade and the lowest levels after subcutaneous administration.

Distribution
The binding of lidocaine to plasma proteins is dependent on the concentration of the drug and the bound fraction decreases with increasing concentration. At concentrations of between 1 and 4 μg free fraction per ml, between 60% and 80% of lidocaine is bound to proteins. Binding is also dependent on the plasma concentration of alpha-1-acid glycoprotein.
LIDOCADREN TEVA RH SY 03.2016
Lidocaine crosses the blood-brain barrier and placenta, supposedly by passive diffusion.

Biotransformation
Lidocaine is rapidly metabolised by the liver, with metabolites and non-metabolised drug being excreted via the kidneys. Biotransformation includes oxidative N-dealkylation, aromatic hydroxylation, cleavage of the amide bond and conjugation. N-dealkylation results in the monoethylglycinexylidide and glycinexylidide metabolites. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine. Approximately 90% of the 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.

Elimination
Studies of lidocaine metabolism after injection of an intravenous bolus have shown that the elimination half-life of this agent is between 1.5 and 2 hours. Due to the high metabolisation rate of lidocaine, any condition that affects hepatic function may alter lidocaine kinetics. The half-life may be prolonged twofold or more in patients with hepatic impairment. Renal impairment does not affect lidocaine kinetics but may increase the accumulation of metabolites.