Caine anesthetics

The compound 4-amino-5-nitrosalicylic acid is one of the building blocks needed for the synthesis of propoxycaine, one of the family of "caine" anesthetics. Some other members of this family of local anesthetics are procaine (Novocaine ), lidocaine (Xylocaine ), and mepiv-icaine (Carbocaine ). 4-Amino-5-nitrosalicylic acid is synthesized from salicylic acid in three steps (See Example 10.9)... 

A recent report from the U.S. National Academy of Sciences estimates than less than 1% of all living species have been characterized. Thus, alkaloid chemistry remains today an active area of research, and innumerable substances with potentially useful properties remain to be discovered. Undoubtedly even the caine anesthetics will become obsolete at some point, perhaps supplanted by newly discovered alkaloids. 

Goserelin (Zoladex), a hormonal antineoplastic drug used to treat breast cancer, is administered subcutaneously in an unusual way. The drag is contained in a dry pellet that is implanted in the soft tissue of the abdomen, where it is gradually absorbed during a period of 1 to 3 months. After a local anesthetic, such as lido-caine, is administered, a large needle (usually 16 gauge) is used to insert the pellet. 

Local anesthetics are positively charged amphiphiles in solution. We have selected hydrochlorides of dibucaine (DBC H ), procaine (PRC H ), tetracaine (TTC H ), and lido-caine (LDC H ). All of these drugs are structurally similar they consist of the substituted benzene ring and tertiary amine moieties, as shown by (VI)-(IX) in Fig. 1. The presence of the positive charge increases the solubility in water and in consequence, the anesthetic efficiency. 

The answer is c. (Hardman, p 340. Katzung, p 437.) Of the listed agents, only bupivacaine is an amide. Allergy to amide-type local anesthetics is much less frequent than with ester-type local anesthetics, such as benzo-caine patients who demonstrate an allergy to one such drug will be allergic to all of them... 

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. 

Excellent and rapid anesthetization of an extremity can be obtained easily. Following insertion of an intravenous catheter in the limb of interest, a rubber bandage is used to force blood out of the limb, and a tourniquet is applied to prevent the blood from reentering a dilute solution of local anesthetic, most commonly lido-caine, is then injected intravenously. This technique fills the limb s vasculature and carries the anesthetic solution to the nerve by means of the blood supply. Because of the pain produced by a tourniquet after some time, this procedure usually is limited to less than 1 hour. The systemic blood levels of drug achieved after tourniquet release generally remain below toxic levels. 

Mechanism of Action A surface or local anesthetic which is not chemically related to the "caine" types of local anesthetics. Decreases the neuronal membrane permeability to sodium ions, blocking both initiation and conduction of nerve impulses, therefore inhibiting depolarization of the neuron. Therapeutic Effect Temporarily relieves pain and itching associated with anogenital pruritus or irritation. 

Classes I, III, and IV all involve transmembrane ion channels Classes I and III involve Na+ channels. Class I compounds are designed to block cardiac Na channels in a voltage-dependent manner, similar to local anesthetics. Not surprisingly, many of these Class I agents are either local anesthetics or are structurally based on local anesthetics. Class I compounds include procainamide (7.15), disopyramide (7.16), amiodarone (7.17), lido-caine (7.5), tocainide (7.18), mexiletine (7.19), and flecainide (7.20). The majority of these compounds possess two or three of the fundamental structural building blocks found within local anesthetics. Propranolol (7.21) is the prototypic Class II agent. Class III compounds include molecules that block outward K channels, such as sotalol (7.22) and dofetilide (7.23), and molecules that enhance an inward Na current, such as... 

FIGURE 13—3. Icon of cocaine. The main mechanism of action is to block reuptake and cause the release of monoamines, principally dopamine (DA), but also norepinephrine (NE) and serotonin (5HT). There is also a local anesthetic action (caine). 

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

Physical therapists may encounter the use of local anesthetics in several patient situations because of their various clinical applications. For example, therapists may be directly involved in the topical or transdermal administration of local anesthetics. As discussed earlier, repeated topical application of local anesthetics may help produce long-term improvements in motor function in patients with skeletal muscle hypertonicity, so therapists may want to consider incorporating topical anesthetics into the treatment of certain patients with CNS dysfunction. Therapists may also administer local anesthetics transdermally, using the techniques of iontophoresis and phonophoresis. Agents such as lido-caine can be administered through this method for the treatment of acute inflammation in bursitis, tendinitis, and so on. 

Local anesthetics -caine Lidocaine, bupivicaine Local anesthetic (12), antiarrhythmics (23)... 

The most popular and widely used local anesthetics are those of the caine family, so called because their names all end with the suffix -caine. They are all chemically related to one another (see Figure 5.1 for examples). Some of the more common members of this family (with brand names in parentheses) include ... 

The tests allow judgement of the propensity of local anesthetics to induce symptoms of hepatic porphyria. The local anesthetics lidocaine, bupivacaine, etido-caine, mepivacaine, prilocaine and pyrocaine belong to this group, but procaine, butacaine, oxybuprocaine, proxymethacaine and tetracaine had no (or very slight) porphyrinogenic effect. 

Usubiaga JE, Wikinski JA, Morales RL, Usubiaga LE. Interaction of intravenously administered procaine, lido-caine and succinylcholine in anesthetized subjects. Anesth Analg 1967 46(l) 39-45. 

Prior application of a topical anesthetic appears to prolong the mydriatic and cycloplegic actions of tropicamide. It was reported that prior instillation of propara-caine 0.5% in blue-green eyes prolonged both the time required for 50% recovery to normal pupil size and the time during which mydriasis was maintained within... 

Most local anesthetic preparations contain benzo-caine. Because benzocaine is poorly absorbed through the skin, it remains localized for a long time however, its effectiveness is unpredictable. Benzocaine has also been known to produce local hypersensitivity reactions.f ... 

A healthy 17-year-old man received an interscalene brachial plexus block using mepivacaine 600 mg and bupiva-caine 150 mg. He became disorientated and showed signs of local anesthetic toxicity, for which he was given midazolam 5 mg. Flumazenil 0.5 mg was given 23 minutes after the end of the procedure, causing opisthotonos. 

Levobupivacaine is the levorotatory isomer, 5(—)-bupiva-caine, of bupivacaine, an amide local anesthetic. 

In a careful meta-analysis, 29 randomized, controlled studies of the incidence of transient radicular irritation were identified (243). Lidocaine and mepivacaine were identified as the two local anesthetics that most commonly cause transient radicular irritation, while prilo-caine, bupivacaine, and ropivacaine had the lowest incidences. Owing to insufficient data, definitive statements could not be made about the effects of the baricity of the local anesthetic, the concentration, and the effect of vasoconstrictors, although all these factors seemed not to be relevant. With regard to intrathecal ropivacaine, the incidence in the formal studies was zero. However, there has been one previous report after intrathecal administration, and one report of transient radicular irritation following epidural anesthesia with ropivacaine the symptoms resolved within 24 hours (244). 

Only one of these therapeutic uses has turned out to be valid, and that is the use of cocaine as a local anesthetic. When cocaine makes direct contact with peripheral neurons, it prevents neural firing, which has the effect of numbing the area. This action is unlike cocaine s effects on the central nervous system. Cocaine was the first local anesthetic and revolutionized surgery. Now, of course, related -caine drugs such as procaine and xylocaine are used more frequently, but because cocaine also constricts blood vessels, it is still used for surgery on areas such as the face, due to the fact that it reduces bleeding as well as pain. 

The toxicity of local anesthetics is related to their potency which is directly related to their hydrop-hobicity. The more hydrophobic drugs such as bupivacaine produce toxicities at concentrations lower than the less potent anesthetics such as lido-caine and mepivacaine. 

Muscle Relaxants, General Anesthetics Cornelius K. Cain, McNeil Laboratories, Inc., Fort Washington, Pa. 

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