Effect of local anesthetics on animal models

Transcription

1 Original article Effect of local anesthetics on animal models Dr. K.Sivaji 1, Dr. G.V.Benerji 1, M. Farid babu 1, D. Rekha kumari 1 1. Associate Professor of Pharmacology, GSL Medical College, Rajahmundry,A.P 1. Professor of Biochemistry KIMS&RF, Amalapuram,A.P 1. Assistant Professor of Biochemistry, KIMS&RF, Amalapuram,A.P 1. Assistant Professor of Biochemistry, KIMS&RF, Amalapuram,A.P Corresponding Author: Dr. K.Sivaji, Associate Professor of Pharmacology, GSL Medical College, Rajahmundry,A.P Abstract Local anesthetics are warranted whenever a clinical procedure causes pain that could be eliminated by their use.their effectiveness is influenced by many factors, particularly the choice of agent and the technique of administration.local anesthesia is useful in a wide variety of clinical situations. It increases patient conform and facilitates patient cooperation during procedures.as a diagnostic aid, it helps localize or identify the source of pain. Use of local anesthesia in the primar care setting can be maximized by an understanding of how anesthetic agents work, the indications for their use, appropriate methods of administration, and techniques to minimize the pain of aministration.several local anaesthetic drugs are available. It is important to become thoroughly familiar with the commonly used ones. Lignocaine (Xylocaine,Lidocaine) is now one of the most popular local anesthetic agents. A comparative study of local anesthetic activity of two clinically used local anesthetic agent Bupivacaine and Lignocaine was done in three species of animal i.e., Frogs, Rabbits, and Guinea pigs by utilizing the experimental models of local anesthesia, testing i.e., plexus anesthesia in forgs, surface anesthesia in Rabbit eye and infiltration anesthesia in Guinea pigs. Both Bupivacaine and Lignocaine produced concentration dependent rapid local anesthesia wheh they are exposed to from lumbar plexus. But in the concentration of 0.1% and 0.2% Lignocaine proucced statistically significant rapid on set of plexus anesthesia compared to similar concentration of Bupivacaine.Two common clinically used local anesthetics Bupivacaine and Lignocaine were tested for local anesthetic activity in the three experimental animal modelsi.e. plexus anesthesia in Frog, surface anesthesia in Rabbits. Infiltration anesthesia in Guinea pigs. Both Bupivacaine and Lignocaine produced local anesthetic effect in all the above mention three experimental models for testing local anesthesia but the following difference were observed as below. Introduction: anesthesia in the primar care setting can be Local anesthetics are warranted whenever a clinical maximized by an understanding of how anesthetic procedure causes pain that could be eliminated by agents work, the indications for their use, appropriate their use. Their effectiveness is influenced by many methods of administration, and techniques to factors, particularly the choice of agent and the minimize the pain of aministration. Several local technique of administration.local anesthesia is useful anaesthetic drugs are available. It is important to in a wide variety of clinical situations. It increases become thoroughly familiar with the commonly used patient conform and facilitates patient cooperation ones. Lignocaine (Xylocaine,Lidocaine) is now one during procedures. As a diagnostic aid, it helps of the most popular local anesthetic agents. localize or identify the source of pain. Use of local 60

2 Bupivacaine (Marcaine) is used when more prolonged anaesthesia isrequired. Levobupivacaine (Chirocaine) and Ropivacaine (Naropin) arerecently introduced drugs with similar properties to bupivacaine bu lesstoxic. Amethocaine is also useful and available in many countries. Local anaesthetic are used mostly in the form of hydrochlorides. The alkaline tissues to release the bases which then combine with the nerve tissues. In infected tissues the acid of the pus makes these drugs less active. Comparative information regarding different clinically used local anesthetics is not available readily especially their relative potency, efficacy and duration. This work is an attempt to throw light in this regard on different laboratory animals, which may be interpolated, to human beings. Materials and methods: The animal models used in this study were:- a) Plexus anesthesia in Frogs b) Surface anesthesia in Rabbits c) Infiltration anesthesia in Guinea pigs Three different procedures have been extensively used in this work. However no other test known provides all the information required, so that one must be prepared to apply several different tests, each useful because of the information it provides. Plexus anesthesia is used to indicate relative speed of onset of anesthesia, rather than duration, since such a preparation presumably undergoes constant deterioration. Corneal anesthesia is an indication not only of anesthetic potentiality, but also of the ability of the agent to penetrate the outermost layers of cells. (Penetration on topical application depends on the presence of significant proportion of un dissociated molecules) In some respects the intra dermal wheal test offers distinct advantages over either of those mentioned above local anesthetic potency on topical application. Observation & results: Lumbar plexus anesthesia: Bupivacaine &Lignocaine produced concentration dependent local anesthesia in Conduction block method in lumber plexus of frog. But the onset of local anesthesia is rapid with Lignocaine compared to the Bupivacaine at the concentration of 0.1% and 0.2 %. Which the p value is statistically significant by Student t Test. However at the lowes concentration of 0.05 there is no statical significance difference between the bupivacaine and lignocane in the onset of anaesthesia (table 1, 2 & 3) Table:1-Effect of 0.5%, 0.1%, 0.2% concentration of Bupivacaine on lumber plexus anesthesia in Frogs: Concentration of Bupivacaine Subject (Frogs) 0.05% 0.1% 0.2% Onset (min) Onset (min) Onset (min)

3 N Total Mean SD SEM Table:2-Effect of 0.5%,0.5%,0.2% concentration of Lignocaine on lumber plexus anesthesia in frogs: Concentration of Lignocaine Subject (frogs) Onset (min) Onset (min) Onset (min) n Total Mean SD SEM n = number of animals, SD= Standard deviation, SEM=Standard error mean 6261

4 Table: 1c Table: 3- Comparison of 0.05%, 0.1%,0.2% concentrations of Bupivacaine and Lignocaine on lumber plexus anesthesia in Frogs: Onset of plexus anesthesia in frogs mean+/- S.E(min) Concentration (o%) Bupivacaine / / /-0.45 Lignocaine / / /-0 t Value p Value Ns <0.05 <0.01 Discussion: A comparative study of local anesthetic activity of two clinically used local anesthetic agent Bupivacaine and Lignocaine was done in three species of animal i.e., Frogs, Rabbits, and Guinea pigs by utilizing the experimental models of local anesthesia, testing i.e., plexus anesthesia in forgs, surface anesthesia in Rabbit eye and infiltration anesthesia in Guinea pigs. Both Bupivacaine and Lignocaine produced concentration dependent rapid local anesthesia wheh they are exposed to from lumbar plexus. But in the concentration of 0.1% and 0.2% Lignocaine proucced statistically significant rapid on set of plexus anesthesia compared to similar concentration of Bupivacaine. Rosrs et al (1993) mentioned that onset of local anesthesia with Lignocaine is fast while with Bupivacaine the onset is moderate. So my results in the plexus anesthesia experiment is like the observation mentioned by Rosers et al(1993) Both Bupivacaine and Lignocaine produced surface anesthesia in the rabbit eye but Bupivacaine produced surface anesthesia at 0.05% concentration. There as Lingocaine produced surface anesthesia in rabbit eye at o.2% concentration suggesting Bupivacaine is more potent than Lignocaine in the literature mentioned that Bupivacaine is local anesthetic agent. So my results in the surface anesthesia experiment are also correlating with the faces mentioned in he literature. Both Bupivacaine and Lignocaine produced infiltration anesthesia wheh injected intradrmally in the guinea pigs. However the duration of infiltration anesthesia with Bupivacaine is more prolong, which is statistically significant in comparison to the duration of infiltration anesthesia after intradermal injection of Lignocaine. Braroy dubenisky et al. (1990) mention that the duration of infiltration anesthesia with Bupivacaine in guinea pigs is prolong in comparison to the duration of infiltration anesthesia with Lignocaine in Guinea pigs. So my results of significant prolonged duration of infiltration anesthesia with Bupivacaine incomparision to Lignocaine are correlating with the results of Braroy might be due to its high lipid solubility in comparison to Lignocaine. Conclusion Lignocaine produced rapid onset of plexus anesthesia in frogs in comparison to the Bupivacaine at concentration of 6362

5 0.1% & 0.2% which is statistically significant. Bupivacaine is more potent than the Lignocaine as a surface anesthetic agent in the rabbit eye because Bupivacaine could produced surface anesthesia in the Rabbit eye at 0.05% concentration onwards. Where as Lignocaine could produce surface anesthesia at concentration of 0.2% Both bupivacaine and Lignocaine produced infiltration anesthesia on intradermal injection in guinea pigs but the duration of infiltration anesthesia in guinea pigs produced by bupicavaine is more prolonged which is statically significant in comparison to the Lignocaine at all the three concentration tested.e.0.05%, 0.1% & 0.2%. Bibliography: 1. A concise review of the basic biology and pharmacology of local analgesia, S 2. Subramanian, M Tennant; Aust Dent J 2005; 50 suppl 2:S23-S30 3. Ritchie JM, Ritchie B, Greengard P: The active structure of local anesthetics. 4. Sharma HL, Sharma KK.. principles of pharmacology., Local anesthetics., Chapter; 16 th, page no: Cousins, M.J., Mather, L.E. Intrathecal and epidural administration of opioids, Anesthesiology, 1984, 61: Foster, R.H., Markham, A. Levobupivacaine: a review of its pharmacology and use as a local anesthetic. Drugs, 2000, 59: Hodgson, P.S., Neal, J.M., Pollock, J.E., and Liu, S.S. The neurotoxicity of drugs given intrathecally, Anesth. Amalg., 1999, 88: Ragsdale, D.R., McPhee, J.C., Scheuer, T., and Catterall, W.A. Molecular determinants of state-dependent block of Na + channels by local anesthetics, Science, 1994, 265: Stevens, R.A., Urmey, W.F., Urquhart, B.L., and Kao, T.C. Back pain after epidural anesthesia with chloroprocaine. Anesthesiology, 1993, 78: Covino, B.G., and Vassallo, H.G. Local Anesthetics: Mechanisms of Action and Clinical Use. Grune&Stratton, New York, Strichartz, G.R., J.M. The action of local anesthetics on ion channels of excitable tissues. In, Local Anesthetics. (Strichartz, G.R., ed.) Handbook of Experimental Pharmacology, Vol. 81. Springer-Verlag, Berlin, 1987, pp Zipf, H.F., and Dittmann, E.C. General pharmacological effects of local anesthetics. In, Local Anesthetics, Vol. 1. International Encyclopedia of pharmacology and Therapeutics, Sect. 8. (Lechat, p., ed.) pergamon press, Oxford, 1971, pp Pickard J Guidelines and the adoption of lipid rescue therapy for local anaesthetic toxicity. Anaesthesia 2009;64:

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