Tetracaine , interaction

Local anesthetics interact with peripheral nerve cell membranes and exert a pharmacological effect [34]. Potential oscillation was measured in the presence of 20 mM hydrochlorides of procaine, lidocaine, tetracaine, and dibucaine (structures shown in Fig. 16) [19]. Amplitude and the oscillatory and induction periods changed, the extent depending on the... 

Kelusky, E. C. Smith, I. C. R, Anethetic-membrane interaction A 2H nuclear magnetic resonance study of the binding of specifically deuterated tetracaine and procaine to phosphatidylcholine, Can. J. Biochem. Cell Biol. 62, 178-184 (1984). 

Shimooka, T., Shibata, A. and Terada, H. (1992). The local anesthetic tetracaine destabilizes membrane structure by interaction with polar headgroups of phospholipids, Biochim. Biophys. Acta, 1104, 261-268. 

Caution [B (D if near term), M] Contra Sulfonamide or salicylate sensitivity, porphyria, GI/GU obst avoid in hepatic impair Disp Tabs SE GI upset discolors urine dizziness, HA, photosens, oligospermia, anemias, Stevens-Johnson synd Interactions T Effects OF oral anticoagulants, oral hypoglycemics, MTX, pheny-toin, zidovudine X effects W/ antibiotics X effects OF digoxin, folic acid, Fe, procaine, proparacaine, sulfonylureas, tetracaine EMS T Effects of anticoagulants monitor EGG and BP for signs of hypovolemia and electrolyte disturbances d/t D skin urine may become yellow-orange may stain contact lenses T risk of photosensitivity Rxns OD May cause NA, drowsiness, HA, abd pain, skin Rxns, lactic acidosis, and jaundice symptomatic and supportive... 

The local anesthetics can be broadly categorized on the basis of the chemical nature of the linkage contained within the intermediate alkyl chain group. The amide local anesthetics include lidocaine (7.5), mepivacaine (7.6), bupivacaine (7.7), etidocaine (7.8), prilocaine (7.9), and ropivacaine (7.10) the ester local anesthetics include cocaine (7.11), procaine (7.12), benzocaine (7.13), and tetracaine (7.14). Since the pharmacodynamic interaction of both amide and ester local anesthetics with the same Na" channel receptor is essentially idenhcal, the amide and ester functional groups are bioisosterically equivalent. However, amide and ester local anesthetics are not equal from a pharmacokinetic perspective. Since ester links are more susceptible to hydrolysis than amide links. 

This effect of cholesterol on the location of guest molecules has been cited for chlorophyll a (36) and tetracaine (5) both molecules with specific biological function. In the present work we have been able to observe this effect over the physiological ranges of temperature and cholesterol concentration. Future experiments with other molecules would clarify if this property of cholesterol is generally applicable to other systems and, furthermore, if it extends to interactions between two molecules solubilized in a membrane. 

This question of direct interaction with nerve proteins or indirect interaction via membrane perturbation has also been tackled by ESR spectroscopy. Two types of labeling have been used fatty acids for lipid labeling and maleimide for frog nerve proteins. The anesthetics used were halothane as an example of a general anesthetic and procaine, lidocaine, and tetracaine as examples of local anesthetics. The latter interact primarily with head groups but can also merge into the hydrophobic hydrocarbon... 

Recently, specific binding to sodium channels was demonstrated for the state-dependent sodium channel blocker [3H]BPBTS [105]. BPBTS is a potent blocker of all sodium channel subtypes tested, including native TTX-resistant channels expressed in mouse sensory neurons. Binding of [3H]BPBTS is inhibited by the local anesthetics tetracaine and lidocaine at concentrations known to interact with channels in the open and/or inactivated state. 

To understand the role of the surface silanols and their contribution to retention, these compounds were separated on a column that was purposely coated to half of the Cjg level of the original Clg (Fig. 5-21b) (coated column had approximately 50% silanol content). If peak tailing is due solely to the silanol interaction, the peak symmetry should be worse than on the fully coated column. But there was no decrease in peak symmetry. In fact, retention of the tetracaine (peak 4) increased slightly while the peak symmetry improved. Thus, it appears that silanols do contribute to retention but the amount of silanols is not the main cause of peak asymmetry. The logical extension of this approach is to separate the compounds on unbonded silica gel, as shown in Figure 5-27c. In this situation, peak symmetry is quite good and retention is decreased. 

Local anesthetics. Anesthetics interact with membranes and increase the gel to liquid-crystalline transition of fully hydrated bilayers. They induce a volume expansion which has the opposite effect of HHP and so they antagonize the effect of HHP on membranes fluidity and volume, making membranes more fluid and expanded. The application of HHP to membrane-anesthetic systems may even result in the expulsion to the aqueous environment. The local anesthetic tetracaine (TTC) can be viewed as a model system for a large group of amphiphilic molecules. From volumetric measiuements on a sample containing e.g. 3 mol% TTC, it has been found that the main tansition at ambient pressure shifts to a lower temperature. The expansion coefficient a drastically increases relative to that of the pure lipid system in the gel phase, and the incorporation of the anesthetic into the DMPC bilayer causes an about 15 % decrease of relative to that of the pure lipid system. The addition of 3 mol% TTC shifts the pressure-induced liquid-crystalline to gel phase transition towards somewhat higher pressures. Larger values for the compressibilities are found for both lipid phases by addition of 3 mol% TTC, and there is no apparent difference in the coefficient of compressibility between the gel and liquid-crystalline phases. Comparison of the IR spectra of DMPC and DMPC/TTC mixtures at pH 5.5 as a function of pressure shows an abrupt... 

Patients anaesthetised with inhalational anaesthetics (particularly cyclopropane and halothane, and to a lesser extent desflurane, enflurane, ether, isoflurane, methoxyflurane, and sevoflurane) can develop cardiac arrhythmias if they are given adrenaline (epinephrine) or noradrenaline (norepinephrine), unless the dosages are very low. Children appear to be less susceptible to this interaction. file addition of adrenaline to intrathecal tetracaine enhances the sedative effects of propofol. 

Clinical examples of this interaction seem to be few and of poor quality (note that the patients were given repeated lumbar punctures, up to four times daily in some instances). E should also be noted that the supporting evidence (human, animal and in vitro studies) dates back to the mid-1940s with nothing more recent apparently on record. Local anaesthetics of the ester type that are hydrolysed to PABA (e.g. tetracaine, procaine, benzo-caine) present the greatest risk of a reaction, whereas those of the amide type (bupivacaine, cinchocaine, lidocaine, mepivacaine and prilocaine) would not be expected to interact adversely. The evidence seems to be too... 

The mechanism of interaction of local anaesthetics with membrane Upids and proteins has been investigated [47], because local anaesthetics such as tetracaine can affect both lipids and proteins of erythrocytes. DSC results confirmed that tetracaine affects not only lipids and proteins but also haemoglobin. The transition at 55-56 °C was attributed to the proteins and the transitions at 68-70 C were attributed to the melting of haemoglobin. Although shifts in transition confirm a moderate involvement with proteins, the packing of the lipids is affected to a much greater extent [47]. 

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