Prilocaine metabolism

Another topical anesthetic, similar to benzocaine, is lidocaine, which is used to relieve the pain of shingles (herpes zoster) infections. Lidocaine is called an amide anesthetic, because it is not an ester (the alcohol is replaced by an amide, the nitrogen group). Amide anesthetics are metabolized by the liver, and are less prone to cause allergic reactions. If an anesthetic has the letter i in the prefix (lidocaine, prilocaine, bupivacaine), it is an amide anesthetic. 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

Y. Azuma, K. Ohura (2004). Immunological modulation by lidocaine-epinephrine and prilocaine-felypressin on the functions related to natural immunity in neutrophils and macrophages. Curr. Drug Targ. Immune, Endocr. Metabol. Disord. 4 29-36. 

The amide linkage of amide local anesthetics is hydrolyzed by liver microsomal cytochrome P450 isozymes. There is considerable variation in the rate of liver metabolism of individual amide compounds, with prilocaine (fastest)... 

Prilocaine is an amide-type LA with a rapid onset and an intermediate duration of action associated with a low toxicity. However, metabolism to ortho-toluidine can cause oxidation of the ferric form of hemoglobin to the ferrous form, creating methemoglobin. In most cases the methemoglobuniemia is benign, but sometimes tissue hypoxia is observed (Eriksson, 1966). 

Prilocaine, which is equal in potency to lidocaine, has a longer duration of action. It is metabolized to o-toluidine, which in toxic doses may cause methemoglobinemia. 

PROCAINE ECOTHIOPATE t plasma concentrations and risk of unconsciousness, and cardiovascular collapse with injections of prilocaine Ecothiopate inhibits pseudocholinesterase, which metabolizes prilocaine Do not co-administer. Use an alternative local anaesthetic not subject to metabolism by pseudocholinesterases... 

The authors concluded that she may have been at increased risk of methemoglobinemia as a result of the metabolic acidosis associated with renal insufficiency, since impaired protein binding of prilocaine could have increased the concentrations of ionized prilocaine. Furthermore, the patient was also taking isosorbide dinitrate, which may have predisposed her to methemoglobinemia. 

Prilocaine is an amide-type LA, with a very low allergenic potential and low toxicity" and is non-vasodilating. Unfortunately, prilocaine is metabolized into ortho-toluidine, a chemical that can induce methemoglobinemia. In doses higher than 500 mg, it can cause cyanosis and reduce the oxygen-carrying capacity of the blood. 

On the other hand the ( )-isomer of deprenyl is a much more potent MAO-B inhibitor than the (+)-isomer. For these reasons racemic deprenyl has been replaced by ( )-deprenyl in clinical practice. In the racemic local anesthetic prilocaine (Figure 26.6) only the R-( )-isomer is metabolized to an aniline derivative (ortho-tolnidine) and to the corresponding para- and ortho-aminophenols that are highly toxic and responsible for met hemoglobinemia. ... 

Akerman, B., Astrom, A., Ross, S., Tele, A. Studies on the absoption, distribution and metabolism of labeled prilocaine and lidocaine in some animal species. Acta Pharmacol. Toxicol. 1966, 24, 389-403. 

Prilocaine (No. 10) represents an interesting situation in that the presence of only one o-methyl group has two consequences. A predictably shorter duration of action because of more facile amide hydrolysis, as compared with lidocaine, and a significant likelihood of methemoglobinemia at higher doses being produced by o-toluidine that results from this amide hydrolysis. The much lower levels of 2,6-xylidine produced from lidocaine (Fig. 13-8) do not produce this hematological toxicity. However, because of more rapid metabolism and the resultant shorter duration of action, overall toxicity of prilocaine is about 40% less than lidocaine. 

No. Prilocaine is metabolized very quickly, whereas bupivacaine is metabolized slowly. Etidocaine, lidocaine and mepivacaine are intermediate. 

Are there any stereochemical requirements of local anesthetic compounds when they bind to the sodium channel receptors A number of clinically used local anesthetics do contain a chiral center (i.e., bupivacaine, etidocaine, mepivacaine, and prilocaine) (Table 16.2), but in contrast to cholinergic drugs, the effect of optical isomerism on isolated nerve preparations revealed a lack of stereospecificity. In a few cases (e.g., prilocaine, bupivacaine, and etidocaine), however, small differences in the total pharmacological profile of optical isomers have been noted when administered in vivo (41,42,43). Whether these differences result from differences in uptake, distribution, and metabolism or from direct binding to the receptor has not been determined. 

Prilocaine was synthesised in 1960 and was found to be very similar to lidocaine. It has a wider safety margin which is probably because it has a lower partition coefficient (Table 15.1) than lidocaine and also the amide bond is more readily enzymatically hydrolysed than that in lidocaine. It does have an additional problem in that the 2-methyl aniline hydrolysis product of metabolism (Fig. 15.10) can cause methaemoglobinaemia, a condition where the oxygen-carrying capacity of blood cells is reduced due to oxidation of iron (II) in haemoglobin to iron (III). Prilocaine has a chiral centre but it is administered as racemate. However, it is only one of the enantiomers which are rapidly hydrolysed in the liver causing toxicity this provides an example of how chirality can influence therapeutic activity. 

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