Local anesthetics in dentistry

PIPA-VALLEJO A, GARCÍA-POLA-VALLEJO Mª J. LOCAL ANESTHETICS IN DENTISTRY. MED ORAL PATOL ORAL CIR BUCAL 2004;9:438-43.

SUMMARY

The purpose of the present paper is to carry out a review of the literature on local anesthetics (LAs), which are the most commonly used drugs in dentistry. Thanks to their improvement over the last few years, they have constituted an enormous advance in both odontological treatment - improving the dental operation in a determinant manner, and the comfort of the patient during these procedures. Furthermore, the addition of a blood vessel constrictor to these local anesthetics has meant that a lower dose of anesthetic can be used, which at the same time acts for longer, providing better conditions for both the patient and dentist. In addition, a study is made of the possible drug interactions, contraindications etc. of the different components in the anesthetic solution, and likewise the possible allergic hypersensitive reactions which can take place and which must be taken closely into consideration when used in the oral cavity.

Key words: Oral local anesthetics, lidocaine, vasoconstrictor, topical buccal anesthesia.

INTRODUCTION

Local anesthetics are those drugs that, on coming into contact with the nerve fiber, interrupt the propagation of the nerve impulse in a lasting and reversible manner. Niemann isolated an alkaloid, cocaine, from coca leaves, which was introduced as a local anesthetic in 1884 by Köller, an ophthalmologist, who also noticed the local vasoconstrictive and ischemic action of this drug (1). In 1905, procaine was synthesized by Einhorm, being the first local anesthetic whose use was not dangerous. This was used until the discovery of lidocaine by Löfgren in 1943 (2).

CHEMICAL STRUCTURE. CLASSIFICATION

LAs are weak bases whose molecules consist of two poles: a lipophilic portion (an aromatic ring) and a hydrophilic element (a secondary or tertiary amine) linked by an intermediate ester or amide chain, or less commonly, by other types of bond (ether, acetone) (3). The existence of the amine group makes it possible for the molecule, when in ionized form, to be soluble in water and able to act on specific receptors, and when in non-ionized form it is soluble in fat and therefore able to cross the different membranes contained within the nerve. Furthermore, the aromatic ring conditions the liposolubility, diffusion and fixation with the LA proteins, which gives rise to a greater or lesser potency and duration (4). The ester or amide bond conditions the speed of metabolisation and the ability to produce high plasmatic concentrations of LA.

We can classify LAs in the following manner, taking into account (5):

- Chemical structure. According to the type of bond (ester or amide) between the aminohydrophilic and aromatic lipophilic group.

- Means of administration. Here we talk of topicalanesthetics(applied in gel or aerosol form) namely benzocaine; and of injected anesthetics in which the anesthesia can be achieved by infiltration (direct injection into the area to be anesthetized, field block or nerve block - lidocaine etc.).

- Clinical use. With therapeutic aims (to eliminate pain), and with diagnostic ends.

- Potency and duration. The greater the concentration of anesthetic, the greater will be its gradient; it will therefore penetrate more rapidly into the nerve to impede the transmission of the nerve impulse. Furthermore, the pH of the solution and the molecular weight of the anesthetic also influence its degree of penetration and effectiveness. Some studies (6), demonstrate that the longest duration of an anesthetic occurs at 3 o'clock in the afternoon, and the shortest in the early hours of the morning and late at night.

ACTION MECHANISM. VASOCONSTRICTORS: ABSOLUTE AND RELATIVE CONTRAINDICATIONS

LAs, when used in appropriate concentrations, inhibit the nerve impulse in a reversible manner when applied to specific areas of the body.

It is believed that LAs act on some specific receptors that are situated in the interior of the Na canals. When the LA comes into contact with its receptor, it obstructs the passage of the Na ions through the canal in the direction of the axoplasm, preventing depolarization and the change in potential. In search of greater effectiveness for LAs, vasoconstrictor agents are usually added to the anesthetic solutions. This combination has constituted a real advance in the field of stomatology, improving the dental operation. The overall aim is to administer the most profound anesthetic with good hematosis in the desired area, to prevent toxic reactions to the local anesthetic agents, on retarding the velocity of absorption into the blood stream and reducing its plasmatic concentration (7, 8), and likewise to prolong its action and produce ischemia in the area of operation. Of all vasoconstrictors, the most commonly used is adrenalin, a physiological catecholamine, and stimulant of the alpha and beta-adrenergic receptors (beta stimulation of the heart can be dangerous in patients with a heart condition, hyperthyroidism, or high blood pressure) (9). The metabolic effects (which are predominately beta) can also be dangerous in diabetic patients (10) (Table 1). Adrenalin also gives rise to undesirable reactions characterized by anxiety, pallor, respiratory difficulty, increased heart rate, palpitations and precordial pain (11).

The adrenalin dosage is limited to 3 micrograms per kilogram, trying not to exceed 0.2mg in healthy patients, although the British National Formulary applies a limit of 0.5 mg emphasizing the extra precaution of not injecting intravascularly. Noradrenalin, which is more stable in solution and requires fewer preservatives, has been tested. It associates with mepivacaine and the maximum total dose should not exceed 0.5 mg, with 0.2 mg proposed as a limit in patients with cardiovascular problems, as it can provoke considerations similar to those of adrenalin. The study of vasopressins is interesting (hormones secreted by the posterior lobe of the pituitary gland) within which stand out: vasopressin, felypressin, and ornipressin. Felypressin seems to be less vasoconstrictive than the sympathomimetic amines and its vasopressive action begins more slowly than with adrenalin (12,13).

Depending on the risk potential and the proportion of morbidity of the medical complications, the contraindications on the use of vasoconstrictors in dentistry can be classified (14) as either absolute or relative.

ABSOLUTE CONTRAINDICATIONS

Heart diseases: unstable angina, recent myocardial infarction, recent coronary artery bypass surgery, refractory arrhythmia, severe uncontrolled or untreated hypertension, untreated heart failure; uncontrolled hyperthyroidism; uncontrolled diabetes; sensitivity to sulfate; cortico-dependent asthma; pheochromocytoma.

RELATIVE CONTRAINDICATIONS

Patients under treatment with tricyclic antidepressants, phenothiazine compounds, MAOI, nonselective beta-blockers, or for cocaine addiction.

A serious complication in the use of vasoconstrictors arises in patients with thyrotoxicosis; it may present in patients with primary or secondary hyperthyroidism, or may be induced by the excessive use of thyroid supplements. LAs containing vasoconstrictors provide a supply of sulfate, and consequently, in some cases of demonstrated allergy, its administration should be contraindicated (15-17). According to studies of 203 patients with asthma by Bush et al. (18), a relationship also exists between patients with sulfate allergy and cortico-dependent asthma. Pheochromocytoma, characterized by the presence of catecholamine secreting tumors should be taken into account (19), and the use of vasoconstrictors must be strictly avoided. Some LAs, such as mepivacaine, that produce acceptable results without a vasoconstrictor may be used, but in any case, the majority of these patients should not receive outpatient dental treatment.

PHARMACODYNAMICS. PHARMACOKINETICS

The ester type anesthetics are metabolized by the hepatic pseudocholinesterases and plasmatic esterases, producing PABA. The amide type LAs metabolize in the liver (prilocaine also in the lungs). LAs are excreted in urine, the ester type 100% metabolized, and the amide type at 90%, the remainder being unmetabolised anesthetic.

PREVENTION OF ADVERSE REACTIONS. DRUG INTERACTIONS

Aside from the vasoconstrictor effects referred to above, we should take into account that when LAs act upon tissues and organs they give rise to an increase in the basal tone of the uterus, have a spasmolytic action on smooth muscle fiber, an effect on body temperature, on the motor plate, on the eye, on the CNS (anxiety, restlessness, or tremor, and death may occur due to respiratory failure) (20), on the cardiovascular system (producing, fundamentally, arteriole vasodilation and hypotension) (21).

Therefore, in order to avoid undesirable reactions to the anesthetic solution, it is very important to undertake a correct clinical history, being informed on drug allergies, the existence of heart disease that may perhaps require antibiotic prophylaxis, asthmatic illness, arterial tension, diabetes, convulsions, surgical interventions, thyroid diseases, pregnancy, drug addiction, hepatitis, AIDS, and antidepressant, anticoagulant and MAOI medication.

The most frequent reactions are caused by either overdose of anesthetic (exceptional and probably caused by intravascular injection on using an inappropriate technique), the accompanying vasoconstrictor, or by drugs used to reinforce the anesthetic, although manifestations caused by hypersensitivity or idiosyncrasy should also be considered.

A good hematological control should be exercised; in cases of alteration in liver function, there is a delay in the metabolisation of the drugs as well as a tendency to hemorrhage. One must also bear in mind that in patients with renal disease the elimination of the anesthetic can be delayed. Uncontrolled diabetes is a candidate for the contraindication for the use of LAs, fundamentally due to their associated vasoconstrictors.

Tricyclic and tetracyclic antidepressants, although useful in the treatment of depression and chronic pain (22, 23), interact with adrenalin and noradrenalin; it is therefore advised not to use them. Furthermore, it is convenient to use anesthetics without vasoconstrictors in patients who are under treatment with MAO inhibitors, since the action of the sympathomimetic amines will be increased, although there are authors (24) who have not detected problems on using anesthetics with vasoconstrictors in dogs treated with MAOI and chlorpromazine. Extreme caution must be taken with cocaine users as this increases the action of the adrenalin (25). The diplopia observed following the use of local anesthetics is related to the sympathetic and parasympathetic effects (26, 27).

Pharmacological interactions are one of the causes of adverse effects that have been attributed to LAs. On the subject of interaction, certain authors (28) draw more attention to the vasoconstrictor than to the actual anesthetic itself. Catecholamine type vasoconstrictors can cause undesirable effects on cardiac function due to the interaction with drugs that will interfere with their point of action, or else with the pharmacokinetics of the catecholamines. Tricyclic antidepressants, MAOI, beta-adrenergic receptor blocking agents etc. act in this way. Beta-blockers are used in cardiovascular pathology to prevent chest angina, high blood pressure and for secondary prevention of myocardial infarction. They can also be used in the treatment of hyperthyroidism, migraines etc. (29). In addition to LAs and vasoconstrictors, there are other components whose function is to preserve the primary elements. Aside from distilled water, sodium chloride (to achieve an isotonic solution), sodium hydroxide (to maintain the pH in the absence of a vasoconstrictor), parahydroxybenzoic phenol esters are used to maintain the sterility of the solution against bacterial and fungal growth.

Likewise, sulfurous anhydride salts (sodium sulfates and bisulfates) are used for their preservative properties in the solution, and at the same time to protect against oxidation of the vasoconstrictor. They are related to hypersensitive reactions and the production of asthma attacks. A critical amount of sodium metabisulfite, between 0.6 and 0.9 mg, is fixed, which when injected extravascularly sets off a crisis in susceptible patients. Likewise, ethylenediaminetetraacetic acid (EDTA) is also used as an antioxidant to increase the sulfate action.

TOPICAL LOCAL ANESTHETICS

Some local anesthetics can be used topically in the oral cavity to produce a surface anesthesia. Its true effect, however, is highly questionable. What is sought with these types of anesthetics is to prepare the oral mucosa in order to alleviate the subsequent effects of the puncture, they are also used to control the nauseous reflex when taking impressions, in the taking of x-rays in the posterior area in patients with excessive nauseous reflexes; temporary alleviation of pain from sores, ulcerations, decubitus ulcers caused by prostheses, gingivitis; as an intrapulpal anesthetic; temporary alleviation of dental pain; in the extraction of radicular remains, highly reabsorbed temporary teeth, in cases of dentinal hyperesthesia, etc. The usual methods of application are - topical application with creams, nebulizers or sprays, ejecting and refrigeration pistols. An oil emulsion in water can be used, based on the eutectic mixture of lidocaine and prilocaine (EMLA) (30). Some sprays contain a 10% concentration of lidocaine, care is therefore necessary with these sprays, above all in children, cachetics, or when applied frequently. Furthermore, some of these topically applied local anesthetics are of the ester type and can provoke hypersensitivity with repetitive use (e.g. amethocaine).

CONCLUSIONS: PROPERTIES OF AN IDEAL ANESTHETIC SOLUTION

The following are the ideal characteristics for a local anesthetic. They should be selective on the nerve tissue; be sufficiently powerful to produce complete anesthesia which does not irritate or harm the tissue where it is applied; have a reversible action within a predictable time; have minimal side effects, and likewise minimal systemic toxicity which will not easily lead to hypersensitive reactions; have a short latency period with the duration of the effect being adaptable to that desired; not produce pain on injection; be compatible with other components in the solution and not easily modified by sterilization processes; not produce habituation; be economic to use; not sensitive to variations in pH; be stable in solution and have enough penetrative properties to be used efficiently as a topical anesthetic.

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