Anesthetics ester-type

Indirectly acting sympathomimetic blocks amine reuptake into nerve endings. Local anesthetic (ester type). Marked CNS stimulation, euphoria high abuse and dependence liability. Tox psychosis, cardiac arrhythmias, seizures. 

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... 

The answer is a. (Hardman, p 338. Katzung, pp 438-439.) Ester-type local anesthetics are mainly hydrolyzed by pseudocholinesterases. Amide-type local anesthetics are hydrolyzed by microsomal enzymes in the liver. Of the listed agents, only lidocaine is an amide and can be influenced by liver dysfunction. 

The answer is d. (Hardman, p T36J The addition of a vasoconstrictor, such as epinephrine or phenylephrine, to certain short-acting, local anesthetics is a common practice in order to prevent the rapid systemic absorption of the local anesthetics, to prolong the local action, and to decrease the potential systemic reactions. Some local anesthetics cause vasodilation, which allows more compound to escape the tissue and enter the blood. Procaine is an ester-type local anesthetic with a short duration of action due to rather rapid biotransformation in the plasma by cholinesterases. The duration of action of the drug during infiltration anesthesia is greatly increased by the addition of epinephrine, which reduces the vasodilation caused by procaine. 

Clinically used local anesthetics are either esters or amides. This structural element is unimportant for efficacy even drugs containing a methylene bridge, such as chlorpromazine (p. 236) or imipramine (p. 230), would exert a local anesthetic effect with appropriate application. Ester-type local anesthetics are subject to inactivation by tissue es-Ltillmann, Color Atlas of Pharmacology... 

Hypersensitivity reactions In patients sensitive to procaine or other ester-type local anesthetics, cross-sensitivity to procainamide is unlikely however, consider the possibility. Do not use procainamide if it produces acute allergic dermatitis, asthma or anaphylactic symptoms. 

B. Allergic reactions occur only to the ester type of local anesthetics. This is because the metabolism of all ester-linked local anesthetics leads to the formation of PABA, which is known to be allergenic to some individuals. Both cocaine and procaine are esters. However, cocaine is not employed in dental procedures. Therefore, the best choice is procaine. 

Contraindications Hypersensitivity to benzocaine or ester-type local anesthetics, perforated tympanic membrane or ear discharge (otic preparations)... 

The amide local anesthetics are widely distributed after intravenous bolus administration. There is also evidence that sequestration can occur in lipophilic storage sites (eg, fat). After an initial rapid distribution phase, which consists of uptake into highly perfused organs such as the brain, liver, kidney, and heart, a slower distribution phase occurs with uptake into moderately well-perfused tissues, such as muscle and the gastrointestinal tract. As a result of the extremely short plasma half-lives of the ester type agents, their tissue distribution has not been extensively studied. 

The local anesthetics are converted in the liver (amide type) or in plasma (ester type) to more water-soluble metabolites, which are excreted in the urine. Since local anesthetics in the uncharged form diffuse readily through lipid membranes, little or no urinary excretion of the neutral form occurs. Acidification of urine promotes ionization of the tertiary amine base to the more water-soluble charged form, leading to more rapid elimination. 

Ester-type local anesthetics are hydrolyzed very rapidly in the blood by circulating butyrylcholinesterase (pseudocholinesterase) to inactive metabolites. Therefore, procaine and chloroprocaine have very short plasma half-lives (< 1 minute). 

The ester-type local anesthetics are metabolized to p-aminobenzoic acid derivatives. These metabolites are responsible for allergic reactions in a small percentage of the patient population. Amides are not metabolized to p-aminobenzoic acid, and allergic reactions to amide local anesthetics are extremely rare. 

The liver, for the amide-type anesthetics, or plasma esterases, for the ester-type, can eliminate large amoimts of local anesthetics. Within 30 to 60 minutes sufficient elimination of the overdose usually occurs to make the CNS stimulation or depression short-lived. Management objectives should therefore center on temporary respiratory and cardiovascular support. Administration of supplemental oxygen usually rapidly restores normal CNS function. In patients in whom cardiovascular collapse is evident, vasopressor therapy may take the form of metaraminol bitartrate 1% (Aramine) given intramuscularly or intravenously. The effect of this potent short-acting vasopressor lasts 20 to 60 minutes, depending on route of administration. 

This ester-type anesthetic is poorly absorbed. Because it contains benzocaine, which has a low water solubility, it is prepared in a base containing petrolatum and sodium carboxymethylcellulose. Eugenol is included for its antiseptic and anodyne properties. Hydroxy-quinoline sulfate is a preservative. This ointment can be directly applied to abraded or ulcerated lesions with minimal systemic effects. It is sometimes used to temporarily relieve denture sores and painful lesions. 

This ester-type anesthetic also contains benzocaine and is prepared in a polyethylene glycol base with flavoring agents added. It is available as a liquid, gel, or spray. The propellant for the spray is A 70. 

This ester-type anesthetic contains butacaine, with benzyl alcohol as a preservative. It is available as an ointment. The maximum dose is 5 ml of a 4% solution or 200 mg. 

This ester-type anesthetic is a combination of tetracaine HCl (2%), butyl aminobenzoate (2%), and benzocaine (14%). Benzalkonium chloride and cetyl dimethylammonium bromide are included as surface-active agents to facilitate the passage of benzocaine into the mucosal tissues. 

Figure 20-15 a Schematic representation of the binding of an ester-type local anesthetic agent to a receptor site. (From Buchi and Perlia, 1960). ... 

Procaine, on the other hand, is an ester-type local anesthetic when it is injected into the organism, it is transformed into N,N-diethylaminoethanol and para-amino-benzoic acid (PABA) when the ester link that binds these two components of procaine is broken. PABA is a well-known allergen. Methyl para-hydroxybenzoate, whose structure is similar to that of PABA, is also called PAB or methylparaben. It is a preservative that binds, like a hapten, to the immunoglobulin E (IgE) on the surface of mast cells and basophils and maybe the cause of the few cases of anaphylactic shock that have been described. Other patients may be allergic to metabisulfite conservative, found in preparations containing adrenaline (epinephrine). 

It may be noted that systemic reactions to ester-type local anesthetics have also been reported to occur among some individuals who are homozygous for atypical serum cholinesterase (Z3, Z4). 

A drawback with the ester-type local anesthetics is the occurrence of allergic reactions, which manifest as dermatitis and systemic effects. 

Some antihistaminics, such as promethazine and diphenhydramine, have local anesthetic properties. They may be used substitutively in patients who are allergic to both amide and ester types of local anesthetics. Some phenothiazine antihistaminics, such as promethazine, have alpha-adrenergic blocking effects. Therefore, like phenothiazine neuroleptics, promethazine may cause orthostatic hypotension. 

Lidocaine (Xylocaine, others), an aminoethylamide is the prototypical amide local anesthetic. Lidocaine produces faster, more intense longer lasting, and more extensive anesthesia than does an eqnal concentration of procaine. Lidocaine is an alternative choice for individuals sensitive to ester-type local anesthetics. 

Discuss the metabolism of ester-type local anesthetics. 

Of the effects listed, the most important in local anesthetic overdose (of both amide and ester types) concern the CNS. Such effects can include sedation or restlessness, nystagmus, convulsions, coma, and respiratory depression. Diazepam is used for seizures caused by local anesthetics, usually without significant effects on ventilation or circulation. The answer is (E). 

The ester group of ester-type local anesthetics is hydrolyzed by plasma (and tissue) pseudocholinesterases. These drugs are poor substrates for acetylcholinesterase the activity of this enzyme does not play a part in terminating the actions of local anesthetics. Individuals with genetically based defects in pseudocholinesterase activity are unusually sensitive to procaine and other esters. The answer is (B). 

Following the introduction of procaine, hundreds of structurally related analogues were prepared and their local anesthetic properties examined. Most of these compounds were prepared for the purposes of enhancing the intrinsic potency and the duration of action of procaine. Among these compounds, tetracaine remains the most potent, long-acting ester-type local anesthetic agents used in spinal anesthesia. 

As a rule, compounds containing an amide linkage have greater chemical stability than the ester types do. In this regard, an aqueous solution of an amino ester-type local anesthetic is more likely to decompose under normal conditions and cannot withstand heat sterilization because of... 

In contrast, allergic reactions to local anesthetics, although rare, are known to occur exclusively with p-aminobenzoic ester-type local anesthetics (18). Whether the formation of PABA on ester hydrolysis is solely responsible for this hypersensitivity remains to be investigated. However, the preservative compounds, such as methyparaben, used in the preparation of amide-type local anesthetics are metabolized to PABA-like substance, p-hydroxybenzoic acid. Thus, patients who are allergic to amino ester-type local anesthetics should be treated with a preservative-free amino amide-type local anesthetic. 

---