Skip to main content

2011 | Lokalanästhetika | OriginalPaper | Buchkapitel

9. Lokalanästhetika

verfasst von : Prof. Dr. Wolfgang Zink, Prof. Dr. Bernhard M. Graf

Erschienen in: Pharmakotherapie in der Anästhesie und Intensivmedizin

Verlag: Springer Berlin Heidelberg

Zusammenfassung

Der molekulare Wirkmechanismus der Lokalanästhetika beruht in erster Linie auf einer reversiblen Blockade spannungsgesteuerter Na+-Kanäle in neuronalen Membranen, wodurch die Entstehung und Fortleitung von Aktionspotenzialen verhindert wird. Obwohl sich eine Vielzahl chemischer Verbindungen mit lokalanästhefrsehen Eigenschaften finden lässt, werden klinisch neben sog. Aminoesterlokalanästhetika hauptsächlich Vertreter der Aminoamide eingesetzt wobei sich beide Gruppen sowohl in der Wirkdauer als auch in Art und Weise ihrer Metabolisierung unterscheiden. Direkt nach Injektion diffundieren die Substanzen zu ihrem Wirkort am Neuron und werden parallel dazu in den Blutkreislauf absorbiert, was einerseits zu einer lokalen Konzentrationsabnah, andererseits aber zu steigenden Plasmaspiegeln führt. Da Na+-Kanäle jedoch nicht nur am peripheren Nerven, sondern im gesamten Organismus an der intra- bzw. interzellulären Informationsübertragung beteiligt sind, muss bei exzessiver systemischer Anreicherung mit einer ubiquitären Beeinträchtigung kommunizierender Zellverbände (v. a. des zentralnervösen bzw. des kardiovaskulären Systems) gerechnet werden. Von der systemischen Toxizität müssen lokale zytotoxische Effekte abgegrenzt werden, die sich substanzspezifisch im Bereich der Injektionsstelle als neuronale und/oder skelettmuskuläre Schäden äußern können.
Literatur
[1]
Zurück zum Zitat Albright GA (1979) Cardiac arrest following regional anesthesia with etidocaine and bupivacaine. Anesthesiology 51:285PubMedCrossRef Albright GA (1979) Cardiac arrest following regional anesthesia with etidocaine and bupivacaine. Anesthesiology 51:285PubMedCrossRef
[2]
Zurück zum Zitat Braid DP, Scott DB (1965) The systemic absorption of local analgesic drugs. Br J Anaesth 37:394–404PubMedCrossRef Braid DP, Scott DB (1965) The systemic absorption of local analgesic drugs. Br J Anaesth 37:394–404PubMedCrossRef
[3]
Zurück zum Zitat Butterworth J, James RL, Grimes J (1997). Structure-affinity relationship and stereospecificity of several homologous series of local anesthetics for the beta2-adrenergic receptor. Anesth Analg 85:336–342PubMed Butterworth J, James RL, Grimes J (1997). Structure-affinity relationship and stereospecificity of several homologous series of local anesthetics for the beta2-adrenergic receptor. Anesth Analg 85:336–342PubMed
[4]
Zurück zum Zitat Catteral WA (2000) From ionic current to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25CrossRef Catteral WA (2000) From ionic current to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25CrossRef
[5]
Zurück zum Zitat Clarkson CW, Hondeghem LM (1985) Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 62:396–405PubMedCrossRef Clarkson CW, Hondeghem LM (1985) Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 62:396–405PubMedCrossRef
[6]
Zurück zum Zitat Englesson S, Grevsten S (1974) The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. Acta Anaesthesiol Scand 18: 88–103PubMedCrossRef Englesson S, Grevsten S (1974) The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. Acta Anaesthesiol Scand 18: 88–103PubMedCrossRef
[7]
Zurück zum Zitat Fozzard HA, Lee PJ et al. (2005) Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des 11:2671–2686PubMedCrossRef Fozzard HA, Lee PJ et al. (2005) Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des 11:2671–2686PubMedCrossRef
[8]
Zurück zum Zitat Graf BM, Abraham I et al. (2002) Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology 96:1427–1434PubMedCrossRef Graf BM, Abraham I et al. (2002) Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology 96:1427–1434PubMedCrossRef
[9]
Zurück zum Zitat Groban L (2003) Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med 28:3–11PubMed Groban L (2003) Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med 28:3–11PubMed
[10]
Zurück zum Zitat Hodgkin AL, Huxley AF (1952) A quantitative descripton of membrane current and its application to induction and excitation in nerve. J Physiol 117:500–544PubMed Hodgkin AL, Huxley AF (1952) A quantitative descripton of membrane current and its application to induction and excitation in nerve. J Physiol 117:500–544PubMed
[11]
Zurück zum Zitat Irita K, Kawashima Y et al. (2005) Critical Incidents during regional anesthesia in Japanese Society of Anesthesiologists-certified training hospitals: an analysis of responses to the annual survey conducted between 1999 and 2002 by the Japanese Society of Anesthesiologists. Masui 54:440–449PubMed Irita K, Kawashima Y et al. (2005) Critical Incidents during regional anesthesia in Japanese Society of Anesthesiologists-certified training hospitals: an analysis of responses to the annual survey conducted between 1999 and 2002 by the Japanese Society of Anesthesiologists. Masui 54:440–449PubMed
[12]
Zurück zum Zitat Mather LE, Copeland SE et al. (2005) Acute toxicity of local anesthetics: underlying pharmacokinetic and pharmacodynamic concepts. Reg Anaesth Pain Med 30:553–566 Mather LE, Copeland SE et al. (2005) Acute toxicity of local anesthetics: underlying pharmacokinetic and pharmacodynamic concepts. Reg Anaesth Pain Med 30:553–566
[13]
Zurück zum Zitat Mulroy MF (2005) Local anesthetics: helpful science, but don't forget the basic clinical safety steps. Reg Anesth Pain Med 30: 513–515PubMed Mulroy MF (2005) Local anesthetics: helpful science, but don't forget the basic clinical safety steps. Reg Anesth Pain Med 30: 513–515PubMed
[14]
Zurück zum Zitat Pollock JE (2003) Neurotoxicity of intrathecal local anaesthetics and transient neurological symptoms. Best Pract Res Clin Anaesthesiol 17:471–484PubMedCrossRef Pollock JE (2003) Neurotoxicity of intrathecal local anaesthetics and transient neurological symptoms. Best Pract Res Clin Anaesthesiol 17:471–484PubMedCrossRef
[15]
Zurück zum Zitat Rosenberg PH, Veering BT et al. (2004) Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 29:564–575PubMed Rosenberg PH, Veering BT et al. (2004) Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 29:564–575PubMed
[16]
Zurück zum Zitat Sztark F, Nouette-Gaulain K et al. (2000) Absence of stereospecific effects of bupivacaine isomers on heart mitochondrial bioenergetics. Anesthesiology 93:456–462PubMedCrossRef Sztark F, Nouette-Gaulain K et al. (2000) Absence of stereospecific effects of bupivacaine isomers on heart mitochondrial bioenergetics. Anesthesiology 93:456–462PubMedCrossRef
[17]
Zurück zum Zitat Valenzuela C, Snyders DJ et al. (1995) Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation 92:3014–3024PubMedCrossRef Valenzuela C, Snyders DJ et al. (1995) Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation 92:3014–3024PubMedCrossRef
[18]
Zurück zum Zitat Weinberg G (2006) Lipid infusion resuscitation for local anesthetic toxicity: proof of clinical efficacy. Anesthesiology 105:7–8PubMedCrossRef Weinberg G (2006) Lipid infusion resuscitation for local anesthetic toxicity: proof of clinical efficacy. Anesthesiology 105:7–8PubMedCrossRef
[19]
[20]
Zurück zum Zitat Zink W, Missler G et al. (2005) Differential effects of bupivacaine and ropivacaine enantiomers on intracellular Ca2+regulation in murine skeletal muscle fibers. Anesthesiology 102:793–798PubMedCrossRef Zink W, Missler G et al. (2005) Differential effects of bupivacaine and ropivacaine enantiomers on intracellular Ca2+regulation in murine skeletal muscle fibers. Anesthesiology 102:793–798PubMedCrossRef
[21]
Zurück zum Zitat ZinkW, Seif C et al. (2003) The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades. Anesth Analg 97:1173–1179PubMedCrossRef ZinkW, Seif C et al. (2003) The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades. Anesth Analg 97:1173–1179PubMedCrossRef
Metadaten
Titel
Lokalanästhetika
verfasst von
Prof. Dr. Wolfgang Zink
Prof. Dr. Bernhard M. Graf
Copyright-Jahr
2011
Verlag
Springer Berlin Heidelberg
DOI
https://doi.org/10.1007/978-3-540-79156-0_9

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.