This is the first of seven pages which constitute a course in local anesthetics. Each page stands on its own, however for a thorough understanding of dental local anesthetics the reader is advised to read the pages in order.
By definition, therefore, every dentist is an expert in the field of local anesthesia, which is an extremely good thing, since without the ability to produce profound numbness, modern dentistry would be all but impossible.
Surprisingly, the first local anesthetic was Cocaine which was isolated from coca leaves by Albert Niemann in Germany in the 1860s. The very first clinical use of Cocaine was in 1884 by (of all people) Sigmund Freud who used it to wean a patient from a morphine addiction. It was Freud and his colleague Karl Kollar who first noticed its anesthetic effect. Kollar first introduced it to clinical ophthalmology as a topical ocular (eye) anesthetic. Also in 1884, Dr. William Stewart Halsted was the first to describe the injection of cocaine into a sensory nerve trunk to create surgical anesthesia. Halsted was an eminent surgeon who had been trained in Britain. He was the first to establish formal surgical training for physicians in America. Prior to that time, surgery was a self taught discipline among US physicians. He also invented and pioneered the use of rubber gloves. Unfortunately, much to his own regret, he began to use cocaine himself and became highly addicted to it. At that time, there was no stigma attached to the recreational use of cocaine, and it gained a following among the elites of the day. Arthur Conan Doyle's Sherlock Holmes was supposed to be an addict, and Holmes kept Dr Watson around as a source for his drugs, as well as for the comic relief he provided.
By the turn of the twentieth century, the addictive properties of cocaine had become clear, and perceived problems with cocaine use began to capture public attention in the United States. The dangers of cocaine use became part of a moral panic that was tied to the dominant racial and social anxieties of the day. Popular newspapers and magazines played into these anxieties by publishing articles pointedly suggesting that the recreational use of cocaine was responsible for the crimes committed by "undesirables" in the underclass. In December of 1914, the Harrison Narcotics Tax Act outlawed the sale and distribution of cocaine in the United States.
Even before the passage of the Harrison Narcotics Tax Act, it had become obvious that while the anesthetic characteristics of cocaine were desirable, the euphoria and subsequent addiction it produced were not! The turn of the century was a tremendous time of scientific progress, and the new discipline of organic chemistry enabled the synthesis of the first analog of cocaine in 1905. (An analog of a chemical molecule is one in which the original molecule is progressively modified to retain and enhance certain holistic characteristics of the original substance while ridding it of other unwanted characteristics.) The first synthetic local anesthetic was procaine, better remembered today by its trade name, "Novocaine".
Novocaine was not without its problems. It took a very long time to set (i.e.. to produce the desired anesthetic result), wore off too quickly and was not nearly as potent as cocaine. On top of that, it is classified as an ester. Esters have a very high potential to cause allergic reactions because the enzyme pseudocholinesterase converts them into para-aminobenzoic acid which is a known allergen. It is estimated that about one in 100 persons who received it developed at least minor allergic reactions to it. Faced with the legal and ethical difficulties associated with the use of cocaine as a local anesthetic, and with the inefficiencies and allergenicity associated with the use of procaine, it is not surprising that most dentists of the day worked without any local anesthetic at all. (Nitrous oxide gas was available during this period.) Today, procaine is not even available for dental procedures.
The first modern local anesthetic agent was lidocaine (trade name Xylocaine®). It was invented in the 1940s. Prior to its introduction, Nitrous oxide gas and procaine (plus alcohol in the form of whiskey) were the major sources of pain relief during dental procedures. Lidocaine proved to be so successful that during the 1940s and 1950s the use of procaine and nitrous oxide gas as primary anesthetic agents all but vanished. (Whiskey somehow survived, but it is no longer used on patients.) Today, nitrous oxide is used principally as an anti-anxiety palliative, and Novocaine is no longer available.
Lidocaine (along with all other injectable anesthetics used in modern dentistry) is in a broad class of chemicals called amides, and unlike ester based anesthetics, amides are hypoallergenic. It sets quickly and when combined with a small amount of epinephrine (adrenalin), it produces profound anesthesia for several hours. Lidocaine is still the most widely used local anesthetic in America today.
Over the next thirty years, a number of other amide local anesthetics were invented, most not differing significantly from lidocaine. The major problem with lidocaine and its analogs is that they cause vasodilation, or the tendency of the local blood vessels to open wider increasing the blood flow in the area. This causes the anesthetic to be absorbed too quickly to take effect. Hence these anesthetics are always mixed with low concentrations of epinephrine which has the opposite effect (i.e. vasoconstriction) and closes the blood vessels down to keep the anesthesia in position long enough to produce long lasting numbness.
Mepivicaine (Carbocaine®) and prilocaine (Citanest®) have much less vasodilative qualities and hence can be used without the epinephrine vasoconstrictor. The advantage to this is that these anesthetics can be used more safely in patients who are taking medications which may interact negatively with the vasoconstrictor. These drugs include certain blood pressure medications (most notably non selective beta blockers) and tricyclic antidepressants (Elevil® and imipramine are two examples). Carpules that do not contain the vasoconstrictor also do not contain a preservative. This eliminates a possible source of allergic reaction. Most patients that believe they are allergic to dental anesthetics are actually allergic to the preservative necessary to stabilize the vasoconstrictor used in most dental procedures. These same patients may discover that they are NOT allergic to mepicicaine or prilocaine without a vasoconstrictor!
Bupivicaine is a special case in dental anesthesia. It is used mostly by surgeons who want to produce very long acting anesthetic effects in order to delay the post operative pain from their surgery for as long as possible. Bupivicaine comes in 0.5% solution with a vasoconstrictor. It is the most toxic of all the anesthetic agents and this toxicity is reflected in its low concentration in the carpules. As noted in the PKa table, it is has a very alkaline (basic) PKa which means that a relatively low percentage of the uncharged base radical (RN) is available for immediate diffusion through the cell membrane. Thus it takes a fairly long time to set. However, once inside the cell membrane, over 80% of the radicals that do diffuse become available for binding to the sodium channel proteins. This high protein binding ability causes the drug to remain active for a long time once it has diffused through the cell membrane. (PKa and its relationship with cell membrane permeability is a concept explained later in this course.) The most frequent use of Bupivicaine is to prevent post-operative pain after surgical procedures. Some dentists will inject a carpule of Bupivicaine after an extraction in order to delay the onset of pain for up to nine hours. This delay effectively reduces the period of severe post operative discomfort which generally tapers off during the first 12 hours post-op.
Prilocaine has the same general PKa as lidocaine, which means that for all practical purposes it can be used in the same way and at the same concentrations as lidocaine, producing about the same anesthetic affect in the same setting time for the same duration. It is, however somewhat less toxic in higher doses than lidocaine, and thus is delivered in a 4% solution which places about twice as much molecular anesthetic in proximity to the nerve as is the case with lidocaine or mepivicaine. In addition, since it has little vasodilatory activity, it may be used without a vasoconstrictor. The higher concentration of anesthetic agent, in combination with a vasoconstrictor, therefore, gives this anesthetic the twin advantages of fast onset of activity with prolonged anesthetic activity due to the larger number of molecules available to cross the cell membrane. Unfortunately, the toxicity of a single carpule of 4% prilocaine is still greater than the toxicity of a single carpule of 2% lidocaine which means that fewer carpules can be used before toxic levels are reached. Higher toxicity also translates into a higher likelihood of prolonged or permanent paresthesia or numbness after using this drug for major nerve blocks.
Articaine is the newest addition to the local anesthetic arsenal and was approved by the Food and Drug Administration in April 2000. It has been in use in Europe since 1976 and in Canada since 1983. Its approval in the US has been delayed by the FDA due to the presence of a preservative which the agency said was unnecessary in single use carpules and was a potential allergen. It was approved when the French company Septodent finally removed the preservative from American shipments.
Articaine has the same PKa and toxicity as Lidocaine, however it is metabolized differently. It has a half life in the body less than 1/4 as long as that of lidocaine and only 1/5 as long as mepivicaine. This means that more of the drug can be injected later in the dental procedure with less likelihood of blood concentrations building to toxic levels. Articaine is formulated in a 4.0% solution with vasoconstrictor. The presence of the vasoconstrictor retards the systemic absorption of the anesthetic allowing higher concentrations of the drug to remain in the area of injection and slowing the absorption into the bloodstream. The higher local concentration of the drug produces a high level of the uncharged radical (RN) to be present at the membrane which brings about very rapid absorption of the drug. (The concept of membrane permeability is discussed on page 4 in this course.) In addition, the benzene ring on the left end of the molecule has been replaced with a thiophene ring. This modification allows for faster and more complete absorption through the nerve cell membrane. The ability of this drug to penetrate barriers is so great that it has been used to penetrate thick bone to produce anesthesia in a way that other anesthetics cannot. Articaine has become the local anesthetic of choice in most countries into which it has been introduced. I have found that it produces profound anesthesia (in most patients) when used as an infiltration (field block) for mandibular premolars and anterior teeth instead of the traditional mandibular nerve block..
With clinical reports of profound anesthesia, fast onset, and success in difficult-to-anesthetize patients, Septocaine has become the most used dental anesthetic brand name in the US, although lidocaine still remains the most used type of anesthetic. Recently, the same articaine formulation became available from a second company under the name Cook-Waite Zorcaine.
Because of its bone penetrating ability, articaine has become popular for producing profound anesthesia in lower premolars and lower anterior teeth using localized field blocks (infiltrations) without resorting to mandibular blocks.
Unfortunately, one complication concerning the use of articaine has arisen. There have been persistent reports of unexplained paresthesia (burning, tingling, and sometimes sharp shooting pains in tissues previously anesthetized with this anesthetic) in a low percentage of patients. This effect has been noted only when articaine is used in major nerve blocks such as the mandibular block. It has not been noted in field blocks. So far, no common factor has been found to explain the link between articaine and persistent paresthesia, however the higher concentration of anesthetic molecules in the anesthetic solution (4% for articaine instead of 2% for lidocaine or 3% for mepivicaine without vasoconstrictor) probably is a factor. The statistics produced for this phenomenon so far have been quite inconsistent. The incidence for persistent paresthesia have ranged between 1 in 5,286 for 2002 to 1 in 45,900 in 2004. The incidence for persistent paresthesia for other types of dental local anesthetic solutions ranged between 1 in 25,850 to 1 in 68,675 during the same time frame (all statistics approximate; CRA June 2005; vol 29, issue 6).
10% of cases of paresthesia lasted for 24 hours or less.
52% of cases of paresthesia lasted 1 to 4 weeks.
29% of cases of paresthesia lasted 1 month to 1 year.
10% of cases of paresthesia lasted for over a year.
The most common link with articaine and paresthesia was administration of mandibular nerve block injections. For this reason a number of dentists have abandoned the use of articaine for mandibular nerve blocks, but still use it for infilatration anesthesia (field blocks) of mandibular anterior teeth and bicuspids.
In defense of articaine, it should be noted that prolonged paresthesia and numbness are very uncommon occurrences, and the chances of getting this type of injury are quite slim. Furthermore, 75% of these cases are associated with the lingual nerve (the one that makes the tongue numb when you get a lower tooth filled). This leads one to question why this should be the case when the vast bulk of the anesthetic solution is actually delivered at the site of the inferior alveolar nerve while only a few drops are delivered to the lingual nerve while withdrawing the needle. If the anesthetic itself is the culprit in the paresthesia, it would make sense if the symptoms should occur more frequently in the distribution of the inferior alveolar nerve (the chin, lip and teeth) rather than in the tongue.
Finally, many dentists are beginning to use articaine for mandibular blocks since this anesthetic produces vastly fewer anesthetic failures than lidocaine or mepivicaine.
Treatment of anesthesia and paresthesia
I am not aware of any specific way to treat the numbness caused by Articaine, other than waiting out the effect. However the disruptive and often painful paresthesia, including the shooting pains in the distribution of the affected nerves may be controlled with certain anti convulsant drugs. One such drug is Lyrica (Pregabalin) 50 mg. three times a day. Two older drugs in this category are Neurontin (gabapentin) and Tegretol (carbamazepine).