PubMed · 10784
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J Duheille. 1976. [Halogen hepatitis].. https://pubmed.ncbi.nlm.nih.gov/10784/
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The effects of several general anaesthetics on the responses evoked by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) were investigated in mouse cortical wedges placed in a two compartment bath and superfused with a nominally Mg(2+)-free Krebs solution. Chloroform (3-6 mM) and halothane (1-3 mM) preferentially antagonized AMPA responses; thiopental (0.1-0.4 mM), diethyl ether (10-30 mM) and isoflurane (1-3 mM) antagonized both AMPA or NMDA responses while ketamine antagonized NMDA responses in a highly selective way. The antagonism of the excitatory amino acid responses exerted by the anaesthetics was non competitive in nature. The inhibition of excitatory amino acid receptor function may be one of the mechanisms whereby general anaesthesia is produced.
The renin angiotensin system is activated during anaesthesia and operation, and the degree to which this activation takes place depends on the hydration and circulation of the patient. The anaesthetic agent used is also important for the activation. Treatment with ACE-inhibitors blunts or abolishes the sympathetic response to anaesthesia/operation. ACEI treatment reduces the need for other hypotensive agents in controlled hypotensive anaesthesia. Some studies suggest that ACEI-treatment should be continued peroperatively on account of its stabilising effect on the circulation to avoid sudden fluctuations in blood pressure and organ perfusion. On the other hand measurements of the cerebral blood flow under anaesthesia in patients treated with ACEI have shown low values in a few patients and this led the authors to recommend discontinuation before anaesthesia. We conclude that controlled clinical trials to evaluate the haemodynamic and neurohumoral consequences of the interaction between ACEI and anaesthetics are required.
Consideration of the interfacial protonation equilibria of membrane-associated amphiphiles indicates that the partition coefficients of the protonated and unprotonated species will differ considerably. The partition coefficients of the charged and uncharged forms of spin-labelled myristic acid in dimyristoylphosphatidylcholine bilayer dispersions have been measured by EPR spectroscopy and found to be approximately 140-fold higher for the protonated acid than for the dissociated salt form. This ratio of partition coefficients is found to be in good agreement with that predicted from the interfacial shift in pKa of the fatty acid on its partitioning into the membrane. The latter was determined from the changes in the EPR spectra of the membrane-associated fatty acid with pH and was found to be +2.1 pH units. The interfacial shifts in pKa for a series of spin-labelled analogues of tertiary amine local anaesthetics have been determined from the pH dependence of the partition coefficients in dimyristoylphosphatidylcholine bilayer dispersions and are found mostly to be in the range of approx. -1.0 to -1.5 pH units, corresponding to a 10- to 30-fold higher partition coefficient of the uncharged base compared with that of the charged ammonium form.