Axcel Lignocaine-P Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Axcel Lignocaine-P Cream provides dermal anaesthesia through the release of lidocaine and prilocaine from the cream into the epidermal and dermal layers of the skin and the accumulation of lidocaine and prilocaine in the vicinity of dermal pain receptors and nerve endings. Lidocaine and prilocaine are amide-type local anaesthetic agents. They both stabilize neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby producing local anaesthesia. The quality of anaesthesia depends upon the application time and the dose.
Axcel Lignocaine-P Cream is applied to intact skin under an occlusive dressing. The time needed to achieve reliable anaesthesia of intact skin is 1-2 hours, depending on the type of procedure. In clinical studies of Axcel Lignocaine-P Cream on intact skin, no differences in safety or efficacy (including anaesthetic onset time) were observed between geriatric patients (aged 65-96 years) and younger patients. The duration of anaesthesia following the application of Axcel Lignocaine-P Cream for 1-2 hours is at least 2 hours after removal of the dressing. The depth of cutaneous anaesthesia increases with application time. In 90% of patients the anaesthesia is sufficient for the insertion of a biopsy punch (4mm diameter) to a depth of 2mm after 60min and 3mm after 120min Axcel Lignocaine-P Cream treatment. Axcel Lignocaine-P Cream is equally effective and has the same anaesthetic onset time across the range of light to dark pigmented skin (skin types I to VI).
The use of Axcel Lignocaine-P Cream prior to measles-mumps-rubella or intramuscular diphtheria pertussis-tetanus-inactivated poliovirus-Haemophilus influenzae b or Hepatitis B vaccines does not affect mean antibody titres, rate of seroconversion, or the proportion of patients achieving protective or positive antibody titres post immunization, as compared to placebo treated patients. Absorption from the genital mucosa is more rapid and onset time is shorter than after application to the skin. After a 5-10 min application of Axcel Lignocaine-P Cream to female genital mucosa the average duration of effective analgesia to an argon laser stimulus which produced a sharp, pricking pain was 15-20 min (individual variations in the range 5-45 min). Reliable anaesthesia for the cleansing of leg ulcers is achieved after an application time of 30 minutes in most patients. An application time of 60 minutes may improve the anaesthesia further. The cleansing procedure should start within 10 minutes of removal of the cream. Clinical data from a longer waiting period are not available. Axcel Lignocaine-P Cream reduces the postoperative pain for up to 4 hours after debridement. Axcel Lignocaine-P Cream reduces the number of cleansing sessions required to achieve a clean ulcer compared to debridement with placebo cream. No negative effects on ulcer healing or bacterial flora have been observed.
Axcel Lignocaine-P Cream produces a biphasic vascular response involving initial vasoconstriction followed by vasodilatation at the application site (see Side Effects). Irrespective of the vascular response, Axcel Lignocaine-P Cream facilitates the needle procedure compared to placebo cream. In patients with atopic dermatitis, a similar but shorter vascular reaction is seen, with erythema occurring after 30-60 minutes, indicating more rapid absorption through the skin (see Precautions).
Pharmacokinetics: The systemic absorption of lidocaine and prilocaine from Axcel Lignocaine-P Cream is dependent upon the dose, area of application and application time. Additional factors include thickness of the skin (which varies in different areas of the body), other conditions such as skin diseases, and shaving. Following application to leg ulcers, the characteristics of the ulcers may also affect the absorption.
Intact skin: Following application to the thigh in adults (60g cream/400cm² for 3 hours), the extent of absorption was approx 5% of lidocaine and prilocaine. Maximum plasma concentrations (mean 0.12 and 0.07μg/ml) were reached approx 2-6 hours after application. The extent of systemic absorption was approx 10% following application to the face (10g/100cm² for 2 hours). Maximum plasma levels (mean 0.16 and 0.06μg/ml) were reached after approx 1.5-3 hours. Plasma levels of lidocaine and prilocaine in both geriatric and non-geriatric patients following application of Axcel Lignocaine-P Cream to intact skin are very low and well below potentially toxic levels.
Children: Following the application of 1.0g Axcel Lignocaine-P Cream in neonates below 3 months of age, to approx 10cm² for one hour, the maximum plasma concentrations of lidocaine and prilocaine were 0.135μg/ml and 0.107μg/ml respectively. Following the application of 2.0g Axcel Lignocaine-P Cream in infants between 3 and 12 months of age, to approx 16cm² for four hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.155μg/ml and 0.131μg/ml respectively. Following the application of 10.0g of Axcel Lignocaine-P Cream in children between 2 and 3 years of age, to approx 100cm² for two hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.315μg/ml and 0.215μg/ml respectively. Following the application of 10.0-16.0g Axcel Lignocaine-P Cream in children between 6 and 8 years of age, to approx 100-160cm² for two hours, the maximum plasma concentrations of lidocaine and prilocaine were 0.299μ g/ml and 0.110μg/ml respectively.
Genital mucosa: After the application of 10g Axcel Lignocaine-P Cream for 10 minutes to vaginal mucosa, maximum plasma concentrations of lidocaine and prilocaine (mean 0.18μg/ml and 0.15μg/ml respectively) were reached after 20-45 minutes.
Leg ulcer: Following a single application of 5 to 10g of Axcel Lignocaine-P Cream to leg ulcers with an area of up to 64cm² for 30 minutes, the maximum plasma levels of lidocaine (range 0.05-0.25μg/ml, one individual value of 0.84μg/ml) and of prilocaine (0.02-0.08μg/ml) were reached within 1-2.5 hours. After an application time of 24 hours to leg ulcers with an area of up to 50-100cm², the maximum plasma levels of lidocaine (0.19-0.71μg/ml) and of prilocaine (0.06-0.28μg/ml) were usually reached within 2-4 hours. Following repeated application of 2-10g Axcel Lignocaine-P Cream to leg ulcers with an area of up to 62 cm² for 30-60 minutes 3-7 times a week for up to 15 doses during a period of one month, there was no apparent accumulation in plasma of lidocaine and its metabolites monoglycinexylidide and 2,6-xylidine or of prilocaine and its metabolite ortho-toluidine. The maximum observed plasma levels for lidocaine, monoglycinexylidide and 2,6-xylidine were 0.41, 0.03 and 0.01μg/ml respectively. The maximum observed plasma levels for prilocaine and ortho-toluidine were 0.08 μg/ml and 0.01μg/ml respectively.