Anesthetics benzocaine, procaine

Hundreds of esters were then synthesized, resulting in esters with substituents on the aromatic ring, esters with the alkyl groups bonded to the nitrogen, and esters with the length of the connecting alkyl chain modified. Successful anesthetics obtained through molecular modification were benzocaine, a topical anesthetic, and procaine, commonly known by the trade name Novocain . 

Poly [ (amino) phosphazenes] have been synthetised by the replacement of chlorine atoms in poly[(dichloro)phosphazene] by amines (Allcock et al, 1966). Drug molecules bearing an amino-group are substituted in the same way, such as the anesthetic molecules procaine, benzocaine, chloroprocaine, butyl-p-aminobenzoyl and 2-amino-4-picoline (Allcock et al, 1982). The poly [(diamino) phosphazene] is not water soluble but this can be achieved by cosubstitution with methylamine, procaine or 2-amino-4-picolino. 

A number of anesthetic molecules, including procaine, benzocaine, chloroprocaine, butyl -aininobenzoate, and 2-aminopicoUne, possess primary amino groups. These groups provide a means for the attachment of the bioactive molecules to a pol3 hosphazene skeleton through the chemistry shown in Scheme I (33). 

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. 

A related approach is to synthesize a polyphosphazene with an amino-drug linked directly to phosphorus through a side-group phosphorus-nitrogen bond. The procaine derivative shown in 3.91 is a typical example designed to release the local anesthetic as an adjunct to dental or minor surgical procedures. Derivatives that contain benzocaine,... 

Methemoglobinemia has been reported with benzocaine, Cetacaine (a mixture of benzocaine, butyl aminobenzo-ate, and tetracaine), cocaine, lidocaine, novocaine, and prUocaine. Acquired methemoglobinemia can result from exposure to chemicals that contain an aniline group, such as benzocaine and procaine, or to those that are transformed to metabolites that contain an aniline group, such as lidocaine and prilocaine. Toxic blood concentrations of local anesthetics, aberrant hemoglobin, and NADH-methemoglobin reductase deficiency are critical... 

An understanding of the metabolism of local anesthetics is important in clinical practice, because the overall toxicity of a drug depends not only on its uptake and tissue distribution but also on how it is deactivated in vivo. The amino ester-type local anesthetics are rapidly hydrolyzed by plasma cholinesterase (also known as pseudocholinesterase), which is widely distributed in body tissues. These compounds can therefore be metabolized in the blood, kidneys, and liver and, to a lesser extent, at the site of administration. For example, both procaine and benzocaine are easily hydrolyzed by cholinesterase into PABA and the corresponding N,N -diethylaminoethyl alcohol. 

Chloroprocaine (N,N -diethylaminoethyl 4-amino-2-chlorobenzoate) is a very short-acting, amino ester-type local anesthetic used to provide regional anesthesia by infiltration as well as by peripheral and central nerve block, including lumbar and caudal epidural blocks. The presence of a chlorine atom ortho to the carbonyl of the ester function increases its rate of hydrolysis by plasma cholinesterase at least threefold compared to procaine and benzocaine. Thus, chloroprocaine may be used in maternal and neonatal patients with minimal placental passage of chloroprocaine. The lower plasma cholinesterase activity in the maternal epidural space must still have sufficient activity for degrading chloroprocaine and, thus, not allowing it to cross the placenta barrier. 

The occurrence of photoallergy to esters of / -aminobenzoic acid was described in the discussion of photoallergic topical drugs (Sect. P.IX). Ordinary contact sensitization is more frequent, described as early as 1949 by Meltzer and Baer (1949). Cross-reactions to other para compounds such as paraphenylenediamine-de-rived hair dyes, azo and aniline dyes, local anesthetics (procaine, benzocaine), sulfonamides, and / -aminosalicylic acid occur. The spectrum of cross-reactions varies from patient to patient (Fisher et al. 1958). Fisher (1977) has emphasized the importance of recognizing impurities in a compound as responsible for certain crossreactions, i.e., benzocaine in glyceryl-/7-aminobenzoic acid (Escalol 106),... 

Occupational problems with topically applied local anesthetics, particularly ester derivatives, have been known for many years (Altomare et al. 1992). Contact allergy to procaine used to be a typical professional disease of dentists due to direct handling (Kanerva et al. 1994). Other affected professions include ophthalmologists and veterinary surgeons. There is an extensive cross-reactivity between all p-amino benzoic acid derivatives, such as procaine, benzocaine and tetracaine, but not to amide derivatives, such as lidocaine. Since the less allergenic amide local anesthetics are used today, the number of occupational cases has declined. The intravenous anesthetic propanidid, a derivative of eugenol (Castelain and Piriou 1980), has caused sensitization in anesthesists by direct and probably also airborne contact (Altomare et al. 1992). 

Benzocaine (ethyl / -aminobenzoate), which has a very simple structure, is used as a mild topical anesthetic in ointments for burns, insect bites, and open wounds. Note that procaine and benzocaine are different esters of the same acid, p-aminobenzoic acid. 

The linkage of local anesthetic drugs, as procaine, benzocaine, chloroprocaine, butyl-p-aminobenzoate and 2-amino-4-picoline, via their amino group to the phosphazene chain was also studied in more detail (Allcock et al, 1982-1986) (Figure 24). Homopolymers and polymers with methylamino groups as co-substituents have been described. 

See more on Lidocaine See more on Anesthetics See more on Procaine See more on Benzocaine See more on Procainamide... 

---