Lidocaine Cocaine

Drugs such as benzocaine, cyclomethycaine, hexylcaine, cocaine, lidocaine, and tetracaine are primarily used for this purpose. 

Absorption from mucous membranes on topical application varies according to the compound. Those that are well absorbed are used as surface anaesthetics (cocaine, lidocaine, prilocaine). Absorption of topically applied local anaesthetic can be extremely rapid and give plasma concentrations comparable to those obtained by injection. This has led to deaths from overdosage, especially via the urethra. 

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... 

Na+ Anticonvulsant drugs Class I antiarrhythmics Diuretic drugs Local anesthetic drugs Carbamazepine, phenytoin, valproic acid lA Disopyramide, procainamide, quinidine IB Lidocaine, mexiletine, phenytoin, tocainide IC Encainide, flecainide, propafenone Amiloride Bupivacaine, cocaine, lidocaine, mepivacaine, tetracaine... 

Bupivacaine Cocaine Lidocaine Procaine Ropivacaine Tetracaine... 

FIGURE 16.4 Chromatoplate picture after elution with two-dimensional system and revelation with modified Dragendorff (bismuth carbonate solntion + potassium iodide -h concentrated HCl) for cocaine, lidocaine caffeine followed by revelation with diazotization reaction by using P-naphthol for benzocaine. 

Denatonium benzoate is the bitterest-tasting substance known. It gets its name from denatured alcohol—alcohol that has been rendered unfit for drinking—and is often used in the denaturing process. Specially denatured alcohol 40, or SD-40, is ethanol that has been denatured by a tiny amount of denatonium benzoate. Denatonium benzoate is an ester of PABA, and is related to lidocaine, benzocaine, novocaine, and cocaine. 

Cocaine and lidocaine instantly produce purple-blue chromatogram zones on a colorless background. 

The color differences between lidocaine and cocaine zones become clearly apparent after 4 h and are stable for about 24 h. They make it possible to identify cocaine and lidocaine in mixtures, even when the two substances are scarcely separated from each other. 

Several topically applied local anesthetics are routinely used by the eye care specialist in certain routine diagnostic procedures and for various relatively simple surgical procedures such as insertion of punctal plugs and surgical vision correction. The first of these to be used was cocaine, in concentrations ranging from 1 to 4% [30]. More modern local anesthetics, however, such as tetracaine hydrochloride and proparacaine hydrochloride, have replaced cocaine as drugs of choice in these procedures. For surgical procedures of a more complex nature, lidocaine hydrochloride and similar local anesthetics as retrobulbar injections have been used [31]. 

A post-mortem examination and a rectal temperature of 41°C (106°F) were recorded. He had needle marks typical of intravenous drug abuse and pulmonary and cerebral edema. Abrasions and contusions of the ankles and wrists were evident from his struggling. Lidocaine was not administered to the victim during the resuscitative attempts. The clinical presentation of cocaine delirium... 

Cocaine is still a drug of choice among many physicians as a topical local anesthetic because the drug has vasoconstrictive qualities (shrinks and stops the flow of blood). Synthetic local anesthetics such as novacaine and xylocaine (lidocaine) have also been discovered and used extensively as a local anesthetic. 

The enzyme is the principal participant in N-demethylation reactions where the substrate is a tertiary amine. The list of substrates includes erythromycin, ethylmor-phine, lidocaine, diltiazem, tamoxifen, toremifene, verapamil, cocaine, amiodarone, alfentanil and terfenadine. Carbon atoms in the allylic and benzylic positions, such as those present in quinidine, steroids and cyclosporin A, are also particularly prone to oxidation by CYP3A4, a range of substrates is illustrated in Figure 7.10. 

Other agents employed for surface anesthesia include the uncharged poli-docanol and the catamphiphilic cocaine, tetracaine, and lidocaine. 

Previously used as component of "Magic Numbing Solution" or TAC Sol (epinephrine 1 2,000, tetracaine 0.5%, cocaine 11.8%) and LET Sol (lidocaine 4%, epinephrine 0.1%, tetracaine 0.5%), which are used as topical anesthesia for repair of minor lacerations. Topical tetracain solutions no longer available... 

Historically, local anesthetics have been known for many years. Cocaine, the first such agent, was isolated in 1860 and introduced for clinical application in 1884. Procaine was developed as a synthetic analog of cocaine in 1905 and lidocaine was synthesized in 1943. The development of new chemical entities as putative local anesthetics remains an ongoing activity in medicinal chemistry. 

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. 

Topical local anesthesia is often used for eye, ear, nose, and throat procedures. Satisfactory topical local anesthesia requires an agent capable of rapid penetration across the skin or mucosa, and with limited tendency to diffuse away from the site of application. Cocaine, because of its excellent penetration and local vasoconstrictor effects, has been used extensively for ear, nose and throat (ENT) procedures. Cocaine is somewhat irritating and is therefore less popular for ophthalmic procedures. Recent concern about its potential cardiotoxicity when combined with epinephrine has led most otolaryngology surgeons to switch to a combination containing lidocaine and epinephrine. Other drugs used for topical anesthesia include lidocaine-bupivacaine combinations, tetracaine, pramoxine, dibucaine, benzocaine, and dyclonine. 

Cocaine did have genuine medical value as a topical (local) anesthetic, but it would be replaced later with similar chemicals (such as novocaine and lidocaine) that did not affect the brain. 

Clinical use Tetracaine is employed by ophthalmologists for surface anesthesia as a 0.5 % solution and by endoscopists for anesthesia of mucous membranes including airways as a 2.0 % solution. For topical anesthesia, a 4.0 % cream of tetracaine can also be used, which is, however, less effective than a lidocaine/prilocaine cream in preventing venipuncture-induced pain in children (van Kan et al., 1997). A combination of tetracaine with adrenaline and cocaine (TAC) is widely used for repair of... 

Lidocaine is chemically similar to cocaine it is also a sodium channel-blocking drug, which is why it is an effective topical pain reliever that is commonly sold over the counter in drug stores. However, in contrast to cocaine, it has no reinforcing, euphoric effect at all, and animals, including humans, will not self-administer it. This confirms the validity of the finding that... 

The caine suffix (lidocaine, procaine, and so on) usually identifies local anesthetics.. The first clinically useful local anesthetic identified was cocaine in... 

A frequently cited example of an important natural-product-derived drag is the neuromuscular blocker d-tubocurarine, derived from the South American plant curare, which was used by South American Indians as an arrow poison (see Chapter 26). Tubocurarine led to the development of decamethonium, which, although structurally dissimilar to tubocurarine, was nevertheless synthesized based on the then prevalent presumption that tubocurarine contained two quaternary nitrogens. Similarly, synthetic local anesthetics, such as lidocaine, benzocaine, and dibucaine, were synthesized to mimic the nerve-blocking effect of cocaine, a natural alkaloid obtained from the leaves of Coca eroxylum, but without the adverse side effects that have led to its abuse. 

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