Local anaesthetics interaction

Preliminary studies [241, 249, 250] of the cardiovascular and sympatholytic properties of prenylamine demonstrated that coronary blood flow and oxygenation could be increased under experimental conditions (in dogs) and that the drug interacted in complex fashion with sympathetically innervated organs, but the picture presented was someudiat confused because of the many uncontrolled variables and limitations of the actual techniques used. Anti-arrhythmic activity of potency comparable with that of quinidine, plus local anaesthetic properties, were also demonstrated [251] but the same worker was notable to reproduce these effects in intact live animals with any consistency. Large doses of the drug actually provoked cardiac fibrillation in some cases. 

Separation of the enantiomers of a series of local anaesthetics through their interaction with dimethyl p-cyclodextrin included In the running buffer. Redrawn from Reference 6. 

Figure 14.11 shows the separation of R and S isomers of a series of structurally related local anaesthetics. Wide separations were achieved for the compounds in this series where it was proposed that the fit of the hydrophobic portion of the analyte into the cyclodextrin was optimal when one of the substituents at the chiral centre was able to interact with the chiral hydroxyl groups on the rim of the cyclodextrin cavity. Table 14.3 shows the association constants calculated for the interaction of the enantiomeric pairs with the dimethylcyclodextrin. The larger the value of K, the... 

ANAESTHETIC DRUGS ANAESTHETICS - LOCAL Other interactions... 

LIDOCAINE PROCAINAMIDE Case report of neurotoxicity when intravenous lidocaine administered with procainamide. No significant interaction expected when lidocaine is used for local anaesthetic infiltration Likely to be an additive effect both may cause neurotoxicity in overdose Care should be taken when administering lidocaine as an infusion for patients taking procainamide... 

Wulf H, Godicke J, Herzig S. Functional interaction between local anaesthetics and calcium antagonists in gui-neapig myocardium 2. Electrophysiological studies tvith bupivacaine and nifedipine. Br J Anaesth 1994 73(3) 364-70. 

A shift in A,max to shorter wavelength is called a hypsochromic effect, or blue shift, and usually occurs when compounds with a basic auxochrome ionise and the lone pair is no longer able to interact with the electrons of the chromophore. Hypsochromic effects can also be seen when spectra are run in different solvents or at elevated temperatures. Spectral shifts of this type can be used to identify drugs that contain an aromatic amine functional group, e.g. the local anaesthetic benzocaine (see Figure 7.9). 

Local anaesthetics and barbiturates appear to prevent the changes in ion permeability which would normally result from the interaction of acetylcholine with its receptor. They do not, however, bind to the acetylcholine binding site. It is believed that they bind instead to the part of the receptor which is on the inside of the cell membrane, perhaps binding to the ion channel itself and blocking it. 

Interactions of local anaesthetics with other drugs are relatively rare and are most likely to occur if both drugs are given intravenously. With the doses and routes of administration used in podiatry, physiotherapy and radiography dmg-drug interactions can be expected to be a rare event. Nevertheless, interactions are possible. Table 12.3 shows some possible drug-drug interactions with lidocaine. 

With which groups of drugs do local anaesthetics produce interactions ... 

The local anaesthetics mentioned in this section are listed in Table 5.1 , (p.91). The interactions discussed in this section mainly involve the interaction of drugs with local anaesthetics used for epidural or spinal anaesthesia. The interactions of lidocaine used asanantiarrhythmicisdealtwith in Antiarrhythmics , (p.243). 

Note that drugs such as adrenaline (epinephrine), which are used with local anaesthetics, may interact with inhalational anaesthetics such as ha-... 

Sprotte G, Weis KH. Drug interaction with local anaesthetics. BrJAnaesth (1982) 54, 242P-243P. 

Mixtures of local anaesthetics are sometimes used to exploit the most useful characteristics of each drug. This normally seems to be safe although it is sometimes claimed that it increases the risk of toxicity. There is a case report of a man who developed toxicity when bupivacaine and mepivacaine were mixed together. Spinal bupivacaine followed by epidural ropivacaine may also interact to produce profound motor blockade. However, the effectiveness of bupivacaine in epidural anaesthesia may be reduced if it is preceded by chloroprocaine. 

Herzig S, Ruhnke L, Wulf H. Functional interaction between local anaesthetics and calcium antagonists in guineapig myocardium 1. Cardiodepressant effects in isolated organs. BrJ Anaesth (1994) 73, 357-63. 

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