Essentials of Local Anesthesia with MCQs KG Ghorpade
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Pharmacology of Local Anesthetics1

 
HISTORY OF DEVELOPMENT OF LOCAL ANESTHESIA
Pain has been in existence ever since human being came into this world. Dental pain is considered to be the worst amongst pain due to ailments. It is but natural to acclaim the discovery of drugs, which controlled pain during dental procedures. The only method available a century ago in control of pain was the use of opium and alcohol. It is worthwhile to read a few lines about those great people who heralded the development of the local anesthesia.
It was in 1842 that, a physician named Crawford Long used ether to cause euphoria, under the influence of which a minor surgery was performed. Although Horace Wells was the one who in 1844 demonstrated the properties of nitrous oxide. It was Joseph Priestly who first brought to notice, the effect of N2O. Horace Wells got one of his own tooth removed under the influence of N2O and it was without any pain!.
In Pre-Columbian times, natives in South America used leaves of coca a local shrub (erythroxylon coca) for mystical, religious, social, nutritional and medical purposes. By chewing the leaves of coca, the natives found it gave them relief from hunger and fatigue. In 1551, use of coca leaves was banned but the invaders later found that without chewing of the leaves, the workers could hardly work in the fields or mine gold. Since it enhanced endurance and promoted a sense of well-being it was distributed three or four times a day to the workers during brief period of rest. These leaves were brought to Europe to extract the active principle. After much experimenting, Gaedicke in 1855 isolated the alkaloid erythroxylin from the coca leaves. Albert Niemann a chemist in 1860 was successful in isolating cocaine from erythroxylin. In the year 1879 von Anrep found that diluted solution of cocaine when injected caused the skin to become numb and the pupils dilated when the solution was dropped on the eye. Sigmund Freud studied the properties of cocaine and wrote a paper highlighting the properties of cocaine. Carl Koller hearing the comments of Dr. Engel about the numbing effect of the crystals of cocaine on tongue hastened to experiment with diluted solution of cocaine on the cornea of his own eye. He was excited about its anesthetic effect and in the same year (1884) demonstrated the effectiveness of cocaine on mucous membrane at a conference in Vienna. Thus Koller heralded the use of cocaine as an anesthetic agent. Finally it was William Halstead who in 1885 administered the first inferior alveolar nerve block using 4% cocaine in solution. Although the cocaine's benefits became popular the toxic and habit-forming properties surfaced. Many fatalities were reported a few years after its introduction. In spite of these disadvantages, cocaine was widely used for nearly 10 years.
Willstatter and associates in 1895 explained the chemical structure, the benzoic acid methyl ester, which initiated further research in benzoic acid esters. Although many synthetic compounds with anesthetic properties were introduced, they were unable to replace cocaine. 2Meanwhile Einhorn after number of years of experimenting with many compounds succeeded in synthe-sizing procaine in 1904. This local anesthetic was less toxic and importantly was not addictive. Procaine became the choice of local anesthetic for the next 40 years.
Erdman, right from 1940 was experimenting with alkaloid gramine and was surprised to find the numbing effect of the drug on the tongue. Probably tasting the chemicals was a way of determining some properties of any chemical. It was Lófgren in 1943 who continued the research work and successfully synthesized lidocaine, an aniline derivative. This heralded a new era of non-toxic anesthetic agent. Lidocaine is being used even today and has found general acceptance as a safe and effective local anesthetic drug. Since then many more anesthetic agents have been developed, some having rapid onset and some showing long duration of action. The research still continues for an ideal anesthetic agent.
 
DESIRED PROPERTIES OF AN IDEAL ANESTHETIC AGENT
  1. The action of an anesthetic agent should be reversible.
    During any dental procedure the purpose of an anesthetic agent is to ensure that the patient does not feel any sensation of pain. The anesthetic effect should be in the teeth and the surrounding supporting structures. After a short duration of time, normal sensation should return in the area of anesthesia.
  2. The anesthetic solution should be compatible with the tissue fluids.
    The anesthetic solution is usually injected into the tissues in the area of nerve distribution. The solution so injected should not act as an irritant to the tissues. The patient should feel comfortable during the deposition, and its absorption.
  3. Onset of action of the anesthetic agent should be rapid.
    Rapid effect of the anesthetic solution in the area is important since neither the patient nor the dental surgeon need to wait for the continuation of treatment. If the waiting period is prolonged before onset of anesthesia the patient may become more apprehensive.
  4. The duration of action should be sufficient for varying procedures.
    The majority of dental procedures undertaken in general dentistry usually lasts from 10 minutes to 30 minutes. If the anesthesia lasts more than 30 minutes the patient is left to wait with the uncomfortable feeling of numbness. Apart from the uncomfortable feeling, the patient may injure his or her lips or check by accidental biting.
  5. The anesthetic solution should possess rapid diffusion property.
    The anesthetic solution when injected in the vicinity of the nerve branches, should diffuse up to the nerve in the shortest possible time. It should be able to diffuse through the periosteum, bone and interstitial tissue. This property of diffusion will minimize the number of needle penetration made during infiltration anesthesia.
  6. It should possess low systemic toxicity.
    All anesthetic agents cause certain amount of excitation and stimulation of central nervous system (CNS) and cardiovascular system. In cases of excess dosage it may result in undesirable effects. Toxicity depends upon the absorption, percentage of anesthetic in circulation and the rate of excretion from the body. An ideal anesthetic should be clinically active in low concentration and possess low toxicity.
  7. There should be rapid excretion from the body.
    This depends upon the hydrolysis of the drug in the blood, liver and excretion in the kidneys. When there is rapid excretion, the anesthetic agent is removed from the circulation and symptoms of toxicity may not be seen.
  8. Should be able to achieve maximum anesthetic effect with minimum amount of dosage.
    The anesthetic agent should be potent even in low dosage. This depends upon the protein binding 3property of the particular anesthetic agent, presence of a vasoconstrictor, technique of administration and the vascularity of the area.
  9. It should be free of allergic reactions.
    Certain anesthetic agents cause allergy, which sometimes could be severe. Apart from anesthetic agents, constituents like vasoconstrictor and preservatives may cause allergic reactions. The amide group of anesthetic drugs do not cause any allergic reactions but preservatives used in anesthetic solution may cause allergic reactions.
  10. It should be stable in solution form with a long shelf life.
    The anesthetic base which are unstable are combined with strong acid to make them stable. When vasoconstrictors are used, preservatives and antioxidizing agents are added to increase the shelf life.
  11. It should not be a habit-forming drug.
    Cocaine, which was being used as an anesthetic agent resulted in habit formation. The preparations available at present are free from addiction.
  12. It should be compatible with other constituents in the anesthetic solution. Many constituents like preservatives, antifungal agents, antiseptics and vasoconstrictors are added to the anesthetic solution to achieve certain desirable properties as the anesthetic agent by itself may not be ideal. These constituents when added together should be compatible with each other and should not intereact and cause undesirable effects.
 
LOCAL ANESTHESIA—TERMINOLOGY
General anesthesia refers to loss of consciousness and the action is on central nervous system. In local anesthesia the action is on peripheral nerves and the patient will be awake. The term analgesia is applied when there is loss of pain sensation alone. Local anesthesia causes loss of pain, pressure, touch and temperature in a localized area. In many of the dental procedures local dental analgesia could be ideal and comfortable, however it will not be possible to achieve selective analgesia by the use of anesthetic drugs. Local anesthesia can be achieved by the following methods:
  1. By reducing the temperature of the area (e.g. spraying of ethyl chloride).
  2. Selective sectioning of nerve fibers.
  3. Permanent or long term loss of sensation by application of chemicals.
  4. Use of drugs to temporarily stop transmission of nerve impulses.
In this book the discussion is restricted to use of local anesthetic drugs in control of pain.
 
CHEMISTRY
Chemically, all anesthetic agents consist of an anesthetic portion, a linkage chain and a secondary or tertiary amino group. Local anesthetic drugs are synthesized by linking various chemical groups to the aromatic portion and the amino groups. The chemical could be an ester or of amide linkage (Fig. 1-1). The drugs thus synthesized are in general viscid liquids or amorphous solids. These components are usually in basic form and are not soluble in water. Hence they are combined with a strong acid to form hydrochloride which is soluble in water (Fig. 1-2).
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Fig. 1-1: General molecular configuration
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Fig. 1-2: Formation of an hydrochloride salt
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All the anesthetics preparations are in acidic form and are stable. In the acidic state, the anesthetics are almost completely in ionized state. It is essential that nonionized free base is required for penetration of lipid membranous nerve tissue. When the anesthetic solution is deposited in the tissues, the abundant tissue fluid which is in basic state dilutes the acidic anesthetic solution to basic state. By this action certain percentage of free base is liberated which is in non-ionized form and will be available for penetration of the nerve membrane. It is important to note that ionized form of the anesthetic drug is also required for blocking the conduction of nerve impulses. The percentage of ionized and non-ionized parts depends upon the surrounding liquid pH and dissociation constant (pKa is approximate by equal proportion of ionic and non-ionic form present in the anesthetic solution which is constant for each anesthetic drug) of the anesthetic drug used (Fig. 1-3). On entering the nerve cell through the cell membrane the non-ionized form dissociates to ionic form and binds with protein in sodium channel. This blocks the sodium infusion and thus the transmission of nerve impulse is blocked (Fig. 1-4).
The percentage of unionized form is higher in amide group of drugs when compared with ester group of drugs. This results in quicker penetration of the nerve membrane and early onset of action. The binding of the ionized form with plasma proteins is a reversible process. When the binding is prolonged the action of the anesthetics lasts longer.
 
Absorption, Metabolism and Excretion
When the anesthetic solution is injected into tissues it spreads in all directions. Part of the solution infiltrates the nerve tissue and part of it gets absorbed into circulation. Once the action of the anesthetic solution on the nerve tissue wears away it is slowly absorbed into circulation. The amount of solution which enters the circulation depends on:
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Fig. 1-3: Cation-Base ratio
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Fig. 1-4: Steps in action of local anesthetic drug
  1. The vascularity of the area into which the anesthetic solution has been deposited—Higher the vascularity higher is concentration of anesthetic solution entering the circulation.
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  2. Presence of a vasoconstrictor in the anesthetic solution—If there is no vasoconstrictor in the anesthetic solution then the solution is quickly absorbed into circulation. If there is a vasoconstrictor then there is slow absorption of the anesthetic solution and its presence in the tissues is prolonged.
  3. The protein binding properties of the anesthetic solution'If the protein binding is prolonged, there is longer lasting anesthesia; at the same time there is slow absorption of part of the anesthetic solution.
As the absorbed anesthetic solution enters the blood, circulation it is distributed to all the parts of the body. The anatomical parts which are highly vascular attract more of anesthetic drug. Central nervous system, lungs, liver, kidney and spleen absorb major portion of the anesthetic solution. The circulating drug gets hydrolyzed in plasma, liver and is excreted through kidneys. Certain percentage of anesthetic drug is excreted through kidney in free form.
Most of the anesthetic agents used belong either to ester groups or to amide group of drugs. In case of ester groups, major portion of the drug is hydrolyzed in the blood plasma within a short period. Pseudocholinesterase present in the plasma converts the drug into para-amino benzoic acid (PABA). The metabolite PABA causes the allergic reaction related to procaine. The metabolites and the unchanged drug are excreted through kidneys.
The amide group of anesthetics is metabolized primarily in the liver, however prilocaine, undergoes certain amount of biotransformation in the lungs. The biotransformation of the amide group take much more time than the ester group. Administration of amide group of anesthetics in the patients suffering from liver diseases should be dealt with caution. In elderly patients due to reduced function of the liver, dosage of the anesthetic solution should be reduced to prevent toxic effects. As in case of ester group of drugs the end products are excreted through kidneys.
 
ANESTHETIC DRUGS
 
Cocaine
Cocaine is derived from leaves of coca plant. It was used as a local anesthetic for a long period of time. Although it has been used for block anesthesia in the form of anesthetic solution, it is more effective as a surface anesthetic. The drug is highly toxic and habit-forming. Overdosage of the drug results in tremors, convulsions, myocardial depression and death may result due to respiratory failure. At present, cocaine is not used in dental practice since better and safer local anesthetics are available.
 
Derivatives of Ester Group of Anesthetics
 
Procaine Hydrochloride (Novocaine, Bayer)
Procaine hydrochloride was synthesized from para-amino benzoic acid in 1904 by Einhorn. The anesthetic proved to be very useful in dental local anesthesia. Procaine is diethyl amino-ethyl ester. The hydrochloride form is water soluble and successfully used for infiltration and block anesthesia. It is not very useful as a surface anesthetic, since its absorption from the surface is poor. Procaine has a vasodilatory action and hence is absorbed quickly from the site of deposition. Adrenaline, in the ratio of 1:50,000 or 1:100,000 is added to the anesthetic solution, which causes vasoconstriction of the blood vessels in the local area and thereby delays the absorption of the anesthetic solution. The anesthetic effect approximately lasts for 2 hours. Procaine is hydrolyzed in the blood by pseudocholinesterase and is in turn excreted through the kidneys. Procaine can sensitize patients and cause allergic reactions.
 
Other Ester Group of Anesthetic Agents
Amethocaine(Tetracaine)
  • Used in 0.5 to 2% concentration
  • More useful as surface anesthetic
  • Not suitable for injections
  • More toxic than procaine.
6Tetracaine (Pontocaine)
  • Used in 2% solution
  • More useful as surface anesthetic
  • Slow onset and longer duration of action
  • Less toxic than procaine.
Propoxycaine (Rovacaine)
  • Less potent and less toxic than procaine.
  • Used in combination with procaine 4% Propoxycaine with 2% Procaine and leverternol in 1: 30,000
  • Rapid onset of action.
2 Chlorprocaine (Nesacaine)
  • Used in 2% solution
  • Potent analgesic
  • Increased toxicity
  • Short duration of action
  • Not a reliable local anesthetic.
 
Meta Amino Benzoic Acid Esters Derivatives
Metabutethamine (Unacaine)
  • Less toxic than procaine
  • Short acting
  • Rapid onset of action.
Metabutoxycaine (Primacaine)
  • Less toxic than procaine
  • Longer duration of action.
 
Benzoic Acid Ester Derivatives
  • Piperocaine (Metycaine)—Similar action as procaine.
  • Meprylcaine (Oracaine)—Faster onset of action.
  • Isobucaine (Kincaine)—Longer duration of action.
 
Anilide Non-ester Group
 
Lignocaine
Anilide non-ester group of drugs are extensively used in Dentistry. The most important advantage of this group of drugs is that they contain amide linkage which does not sensitize the patients unlike ester group of drugs. The amide group of drugs are more potent and equally toxic. The first form of anesthetic from this group was lignocaine and was synthesized by Nil Lofgren in 1943. Since that time it has become most popular and widely used anesthetic drug in Dentistry. It is used as a hydrochloride salt and is equally effective both for injections and surface anesthesia. The drug is used in 2% solution and since it has a vasodilatory effect it is rapidly absorbed into the blood stream. To retain the solution in the local area, vasoconstrictors are added which reduces rapid absorption and prevents chances of toxicity. Although the maximum total dosage is 25 ml of 2% solution (500 mg) with adrenaline, 15 ml of solution can be safely used in healthy patients. In most instances, for any procedure performed in dental office, a dentist rarely uses more than 6 to 8 ml of anesthetic agent. This gives a high safety margin. The lignocaine is hydrolyzed in liver, which is then excreted along with part of unchanged drug through kidneys. Lignocaine in medical practice is used in the dosage of 60 to 100 mg i.v. to correct ventricular arrhythmias.
In large doses the drug has a depressive action on the myocardium. Majority of the anesthetic drugs cause initial excitation of CNS but in case of Lidocaine the first reaction to overdosage is that of depression which is clinically noticed as feeling sleepy by the patients.
 
Mepivacaine (Carbocaine, Isocaine, Arestocaine)
Mepivacaine, a derivative of xylidine was introduced in 1960. This drug has a similar action as lignocaine and is used in 2% solution with 1:80,000 adrenaline. Although the action is similar to lignocaine its action is shorter compared to lignocaine. As mepivocaine has a diminished vasodilatory effect, it can be used without a vasoconstrictor in 3% solution. Without vasoconstrictor the drug has a long shelf life. For 2% solution with vasoconstrictor, the maximum dosage should be 300 mg or 15 ml. Mepivocaine is less toxic compared to lignocaine but is not useful as a topical anesthetic.
 
Bupivocaine (Monocaine)
This is a derivative of amide group and is four times more potent than lignocaine. It has a slow rate of onset 7and the anesthetic effect lasts for a longer duration. Bupivocaine can be used in minor oral surgical procedures lasting more than 1½ hrs. Due to its longer duration of action the postoperative pain is also controlled. It has a vasodilatory action on blood vessels and hence should be used along with a vasoconstrictor. It is used in 0.5% solution with 1:200,000 epinephrine. Its use in pregnant women is contraindicated since it may cause cardiac complications in cases of accidental intravenous injections.
 
Prilocaine (Citanest)
Prilocaine differs from lidocaine in that it is a toluidine derivative. It is the most recent anesthetic agent introduced from the amide group. Prilocaine is less potent and less toxic. It has a prolonged action. The diminished toxic effect may be due to its rapid metabolism in the liver. Large doses of prilocaine can result in methemo globinemia. It is contraindicated in children and pregnant women. The drug is metabolized in liver and lungs. It is used in 4% solution with 1:200,000 epinephrine.
 
Etidocaine (Durannt)
Etidocaine is a derivative of amide group and its action resembles that of lidocaine, and is used in 1.5% solution with 1:200,000 epinephrine. The duration of action is more compared to lidocaine.
 
Butamilicaine Phosphate (Hostacain)
This is derived from amide group and has a similar action compared to lignocaine except that the vasodilatory effect is less. It is used in combination with 1% procaine (Hostacain SP). The availability is 2% solution with 1:50,000 adrenaline. Hostacain NOR 2% solution with non-adrenaline in 1:25,000 concentration is also used. Hostacain SP has a longer duration of action than Hostacain NOR. Both these preparations were available in India for some time but later were withdrawn from the market.
 
Articaine HCL
Articaine is an amide derivative introduced in Europe in 1976. Its use in USA was approved in the year 2000. This drug preparation is not available in India. Articaine although an amide derivative also contains an ester component. Articaine is 1.5 times more potent than Lidocaine. It has vasodilatory action like other amide group of drugs. The onset on action of Articaine is faster and gets quickly excreted.
It is available in 4% solution with 1:100,000 and 1:200,000 adrenaline. The advantage of this drug is its supposedly excellent infiltrating properties. It is claimed that all the teeth could be anesthetized by infiltration alone. As infiltration anesthesia is the safest method of administration of local anesthesia, this drug Articaine may prove to be highly valuable.
 
Centbucridine
This anesthetic drug is a quinoline derivative and has been found to be as effective as lignocaine. It has been extensively tried as a local anesthetic in India. The drug has no serious side effects and no adverse effect on cardiovascular system. Even when overdose is attained there has been no untoward effect on CNS. The effect on CNS is stimulation and no depression has been noticed.
 
Diphenhydramine
Diphenhydramine an antihistaminic agent has been used as an effective local anesthetic in patients who are allergic to regular anesthetic drugs. The onset of action is faster but at the same time the effect lasts for a shorter duration. Control of pain is not very profound as in other anesthetic drugs but all minor procedures can be effectively managed.
 
Anesthetic Drugs for Topical Use
Many anesthetic agents are not water soluble and as such cannot be used for injections into the tissues. These 8agents when mixed with alcohol or glycol act as excellent surface anesthetics. When such preparations are applied over mucous membrane they readily penetrate the mucous membrane and anesthetize the terminal nerve endings. This results in surface anesthesia and the initial needle penetration becomes painless. To be effective, the topical anesthetic agents have to be dispensed in higher concentration. They are available in gelly, ointment, viscous liquid and spray form. Since there are no added vasoconstrictors, the anesthetic drugs get quickly absorbed into circulation. If one is not cautious this may lead to toxic levels in the blood. Surface anesthetics are not effective on skin surface.
 
Benzocaine
This is an ester of para-amino benzoic acid. As it is not water-soluble it is not suitable for injections. However preparations of benzocaine act as excellent surface anesthetics when applied over any type of mucous membrane. This ester group of drugs due to its poor absorption, does not cause toxicity due to overdosage. It is dispensed, as gel, gel patch and in spray form.
 
Lidocaine
Lidocaine can be used for both surface application and injections. For surface anesthesia the free base form of lidocaine which is not soluble in water, can be used. For injections the water soluble hydrochloride salt is used. It is available in the form of gelly (2%), topical solution (4%), ointment (5%), viscous liquid (2%) and aerosal spray (10%). Since no vasoconstrictors are added it may get quickly absorbed into circulation and result in toxic reactions. It should be used in moderate dosage.
 
Dyclomine
This is a ketone derivative and differs from other anesthetic agents. Its systemic absorption is poor as it is not water soluble. Onset of action is slow but the effect lasts for a longer duration. It is dispensed in 0.5% solution.
 
Cocaine
This naturally occurring substance is an excellent surface anesthetic. Although this drug has been used for injections for number of years it is not suitable due to its high toxic effects and habit-forming properties. Although the anesthetic agents in general are vasodilators, cocaine causes vasoconstriction. It has a quick onset and longer duration of action. As safer drugs are available, this is not being used in dentistry.
 
Eutectic Mixture of Local Anesthetic (EMLA)
A combination of 2.5% lidocaine and 2.5% prilocaine, EMLA is dispensed in cream form. EMLA when applied to surface of the skin, produces effective surface anesthesia. As there is slow penetration, it has to be applied one hour before the procedure. It is occluded over the skin under a dressing. The anesthetic effect lasts 2 to 3 hours. Although EMLA is mainly indicated for extraoral use it has also been found to be effective intraorally. In dentistry loose teeth extraction and minor surgery in children can be done with the use EMLA.
 
Vasoconstrictors
Vasoconstrictors are added to local anesthetic solution in order to:
  1. Delay the absorption of the anesthetic drug from the site of deposition so that the anesthetic effect can be prolonged.
  2. Reduce the rapidity of absorption in order to prevent accumulation of the drug in the blood circulation to toxic levels.
  3. Control bleeding in the area of surgery.
The above factors depend upon the vascularity of the area where the solution is deposited. As the mucosal tissue in the oral cavity has abundant vascularity, the addition of vasoconstrictor is beneficial. The concentration of the vasoconstrictor used depends upon the potency and toxicity of the drug. For dental use, concentration of epinephrine varies between 1:50,000 and 1:200,000. It has been observed that 1:100,000 9concentration is sufficient for effective duration of anesthesia and also to reduce toxicity.
Use of anesthetic solution with vasoconstrictor in patients with cardiovascular disease was thought to cause an increase in blood pressure which the patient may not tolerate. The amount of vasoconstrictor used in local anesthetic solution is so low that its effect on cardiovascular system is negligible. This has been confirmed by many authors who have opined that careful injection of 2% solution after aspiration should not cause untoward action on the cardiovascular system. It is interesting to note that in a patient under anxiety and stress, there is an equal amount of adrenaline released into circulation endogenously. What is required in cardiovascular patients is careful premedication and prevention of intravascular injection while administering local anesthesia. As a guideline, the ‘New York Heart Association' recommends that in one session not more than 0.2 mg of epinephrine should be administered in a healthy adult. This amounts to 10 ml of anesthetic solution with 1:50,000 adrenaline or 20 ml with 1:100,000 adrenaline. A patient with organic heart, should not receive more than 0.04 mg of epinephrine.
 
Adrenaline (Epinephrine)
Adrenaline is released from adrenal medulla and can be extracted from mammalian adrenaline glands or it can be synthetically manufactured. There are two types of adrenergic receptor namely, alpha and beta-receptors. Alpha receptors are related to excitary effect and beta-receptors are related to inhibitory action. Adrenaline acts on both the receptors, which results in dilatation of blood vessels in skeletal muscles and myocardium, while the vessels in skin and mucous membrane are constricted. The effect on myocardium is increase in heart rate and cardiac output. Epinephrine interacts with tricyclic antidepressant drugs and hence its use in such patients may be avoided. Local anesthetic with vasoconstrictor is sometimes used for infiltration during surgery under general anesthesia to reduce the bleeding in the area of surgical incision. General anesthetics like cyclopropane, ethyl chloride and halothane sensitizes myocardium in the presence of adrenaline and results in ventricular fibrillations. Hence, such infiltrations should always be done with the approval of the anesthetist. To reduce such complications, anesthetic agents with vasoconstrictor felypressine can be used.
 
Noradrenaline (Levarterenol)
Noradrenaline is basically released by sympathetic postganglionic neurons and also to a small extent from adrenal medulla. It has a vasoconstrictor effect on vessels of skin and mucous membrane resulting in peripheral resistance. Its vasoconstrictor effect is comparatively less than epinephrine, although the effect lasts for longer duration. Toxic effects are similar to epinephrine except that norepinephrine causes severe hypertension. It is used in anesthetic solution in the concentration of 1:80,000 to 1:25,000.
 
Nordefin (Cobefrin) and Phenylephrine (Neophryn)
These are other sympathomimetic drugs which have vasoconstrictor action similar to that of adrenaline. The adverse reaction of adrenaline on cardia is not seen when the above two drugs are used. Its vasoconstrictor effect is less compared to adrenaline, while the toxic effects are same as that of adrenaline.
The other drugs that can be used apart from sympathomimetic amines as vasoconstrictor are hormones of posterior lobe of pituitary which are vasopressin, fellypressin (phenyl pressine, octapressin) and ormipressin. Vasopressin is a natural hormone whereas fellypressin and ormipressin are synthetic preparations. These preparations have similar action as that of adrenaline except that they are slow in onset of action and have prolonged effect. They can be safely used for infiltration during general anesthesia without the risk of ventricular fibrillation. They can also be safely used when tricyclic drugs are being used. They are contraindicated in pregnant women as it may cause hypoxia of placental circulation. Prilocaine 3% with fellypressin in the concentration of 0.03 per ml i.v has been successfully 10used in dental practice. Its safety margin in cardiac patients is quite high and hence can be safely used in such patients.
 
CONSTITUENTS OF LOCAL ANESTHETIC SOLUTION
  1. Anesthetic base
  2. Vasoconstrictors (may or may not be present)
  3. Reducing agents
  4. Preservative
  5. Antifungal agent
  6. Vehicle
  1. Local anesthetic compound in basic form is unstable and is not water soluble, but in basic form it is highly lipophilic and thus can quickly penetrate the nerve tissue. Since the free base is unstable, it is combined with a strong acid to obtain a hydrochloride salt which is soluble in water. In solution form, the pH of the anesthetic drug is marginally acidic and is stable. Addition of a vasoconstrictor to the anesthetic solution makes it more acidic. When the anesthetic solution is injected into tissues the abundant interstial tissue fluid, which is normally basic in nature, hydrolyzes the small volume of anesthetic solution and the free base gets liberated. For the free base to be quickly available, the pKa of the anesthetic drug should be lower and pH of the solution higher. pKa is approximate by equal proportion of ionic and nonionic form present in the anesthetic solution which is constant for each anesthetic drug. Local anesthetic is not effective in inflamed and infected region as the tissue fluid in that region is slightly acidic. This results in ineffective hydrolysis of the anesthetic solution.
  2. Vasoconstrictors—Addition of vasoconstrictors and their action has already been discussed. In some preparations, vasoconstrictors are not added and the anesthetic drug is used as plain solution. When plain anesthetic solution is used there will be quick absorption and short duration of action. Chances of overdosage should be kept in mind.
  3. Reducing agents—Vasoconstrictors used in anesthetic solution are unstable. They might get oxidized and discoloration of the solution occurs. To prevent this, small quantity of sodium metabisulphite is added to the anesthetic solution. Sodium metabisulphite has greater affinity to oxygen compared to the vasoconstrictors and thus prevents its oxidation. Sulphites may result in allergic reactions. In some anesthetic preparations capryl hydro-cuprinotoxin is added as a preservative as this does not cause any allergic reactions.
  4. Preservative—Preservatives are added to anesthetic solution to maintain the sterility and to increase their shelf life. Usually methyl or propyl paraben is used as preservative. Parabens are known to cause allergic reactions.
  5. Antifungal agents—A small quantity of thymol is added to anesthetic solution to prevent any fungal growth.
  6. Vehicle—Ringer's solution is used to dissolve all the above constituents and render the anesthetic solution compatible with tissue fluids.