Loca Anesthetics--Vasoconstrictors

This is the second 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.

<==Anesthetic agents and their history

Toxicity and dosage==>

Vasoconstrictors

No matter how quickly an anesthetic agent can enter a nerve, the local blood vessels begin to absorb the unused anesthetic as soon as it is injected. In order to slow this process down, manufacturers of these solutions add a substance that in low concentrations acts to cause the local blood vessels to constrict, or narrow down. This restricts the amount of blood and plasma entering and leaving the site of the injection which has the net effect of slowing the vascular absorption of the anesthetic solution. This keeps the unused anesthetic solution in place longer and prolongs the action of the drug. The substance used to do this is called a vasoconstrictor (vaso refers to blood vessels and constriction means to close down). The vasoconstrictor used is the naturally occurring hormone epinephrine or one of its analogs called levonordefrin. Epinephrine is an ideal vasoconstrictor because it is manufactured naturally by the body as adrenaline, sometimes called the "fight or flight hormone". In addition to causing a constriction of blood supply, if it enters the general circulation it can cause an increased heart rate and stronger heart beat, along with a feeling of nervousness. These side effects account for the "rush" that some people feel after receiving an anesthetic shot.

The downside to vasoconstrictors

Most anesthetic solutions are sold with added vasoconstrictor. Only two, mepivicaine and prilocaine are sold with or without vasoconstrictor (prilocaine is sold under the trade name Citanest®). Mepivicaine and prilocaine have the advantage of producing only minor vasodilation and, though both are short acting without their vasoconstrictor added, they still produce adequate anesthesia for short procedures. The major advantage of using an anesthetic without a vasoconstrictor is that there are virtually no interactions with other drugs the patient may be taking. Vasoconstrictors may not be used with certain types of blood pressure medications or tricyclic antidepressants.

The use of vasoconstrictor does carry one additional penalty for the practitioner. These naturally occurring hormones are not very stable, and must be stabilized by the addition of an acidic preservative. The presence of the preservative can lower the PH of the anesthetic solution to the range of 3.8 to 5.0, thus reducing the amount of the neutral basic radical (RN) and slowing the onset of action of the anesthetic. This effect is, thankfully not especially significant, and anesthesia with vasoconstrictor is far and away the most popular choice among practitioners when other clinical considerations permit its use. Carpules that do not contain vasoconstrictor do not contain preservatives either. This is an important point, since it is most frequently the preservatives, and not the anesthetics themselves which play a roll in allergic reactions.

Vasoconstrictors are also not used in any body area in which the blood supply must "double back" on itself. This includes such blind ended appendages as the tip of the nose, or the fingers or toes. In these areas, a vasoconstrictor may block all blood flow to the appendage causing tissue necrosis (death of the tissue).

Finally, the preservatives necessary to stabilize the vasoconstrictor are paraben derivatives, and these can cause allergic reactions. There has never been a documented case of allergy to the modern amine based anesthetics themselves, however, many people are allergic to to the preservatives associated with the vasoconstrictor. If you believe that you are allergic to dental anesthesia, ask the dentist to use mepivicaine or prilocaine without vasoconstrictor.

Vasoconstrictor concentrations

The concentration of vasoconstrictor in any given carpule of anesthesia is denoted by a ratio of vasoconstrictor per mL of solution. For example, a solution may be labeled as 1:100,000. This concentration represents 1000mg/100,000mL or 0.01mg/mL, or 1 gram per 100 Liters. A 1:1000 solution translates to 1 mg vaoconstrictor per mL of solution, or 1 gram per Liter. Here are some others:

CONCENTRATION	DOSAGE EQUIVALENCE	PERCENT
1:1,000	1mg/mL	0.1%
1:10,000	0.1mg/mL	0.01%
1:100,000	0.01mg/mL	0.001%
1:200,000	0.005mg/mL	0.0005%

Most anesthetic solutions contain the minimum amount of anesthesia necessary to constrict local blood vessels and prolong the action of the anesthetic. Some, however, contain a higher concentration of vasoconstrictor for use in controlling bleeding for specific purposes, such as periodontal surgery. For example, general purpose lidocaine contains epinephrine in the amount of 1/100,000 for producing profound, prolonged anesthesia. However, lidocaine also comes with epinephrine at twice the normal concedntration (1/50,000) used mostly by periodontists who need to control gingival bleeding during surgery.

Indications and contraindications for vasoconstrictor

Drugs and conditions of concern to the dentist

The use of vasoconstrictor in dentistry has been shown over time to be very safe for almost all patients. In fact, the use of vasoconstrictor is highly recommended due to the increase in efficacy and longevity of dental anesthesia.

There are no absolute contraindications to the use of vasoconstrictors in dental local anesthetics, since epinephrine is an endogenously produced neurotransmitter. In 1964, the American Heart Association and the American Dental Association concluded a joint conference by stating that “the typical concentrations of vasoconstrictors contained in local anesthetics are not contraindicated with cardiovascular disease so long as preliminary aspiration is practiced, the agent is injected slowly, and the smallest effective dose is administered."

Still, there are a few situations in which the use of vasoconstrictor should be reduced.

The California dental association provided some of the following information:

Conditions in which vasoconstrictor should be avoided or kept to a minimum

Uncontrolled hypertension
Uncontrolled hyperthyroidism
Patients with angina
patients who have recently had a myocardial infarction
Patients taking NON SELECTIVE Beta Blockers (see table below)
Patients taking tricyclic antidepressants (See table below)

Note that patients with hyperthyroidism or hypertension who’s conditions are properly stabilized with medication (except non selective beta blockers) may be anesthetized with reasonable doses of anesthetic solution containing vasoconstrictor.

The following is a list of non selective beta blockers. If the patient is taking one of these, vasoconstrictor should be avoided

carteolol (Cartol)
carvedilol (Coreg)
labetolol (Normodyne, Trandate)
nadolol (Corgard)
penbutolol (Levatol)
pindolol (Visken)
**propranolol (Inderal)**
sotalol (Betapace)
timolol (Blocarden)

The following is a list of tri-cyclic antidepressants. If the patient is taking one of these, the amount of vasoconstrictor should be restricted to no more than 3 carpules of 1/100,000

amitriptyline (Elavil)
amoxapine (Asendin)
clomipramine (Norpramin)
doxepin (Sinequan)
imipramine (Tofranil)
nortriptyline (Aventyl, Pamelor)
protriptyline (Vivactil)
trimipramine (Surmontil)

Cocaine IS ALWAYS DANGEROUS WHEN COMBINED WITH A VASOCONSTRICTOR. Patients strung out on cocaine are at risk for fatal arrhythmias and must be treated with extreme care.

Vasoconstrictors are NOT contraindicated (ie. they are acceptable within accepted guidelines) if the patient is taking drugs within the classifications below:

Selective Beta blockers

acetutolol (Sectral)
atenolol (Tenormin)
betaxolol (Kerlone)
bisoprolol (Zebeta)
esmolol (Brevibloc)
metoprolol (Lopressor)

Miscellaneous Antidepressants

buprion (Wellbutrin)
maprotiline (Ludiomil)
mirtazapine (Remeron)
nefazodone (Serzone)
trazodone (Desyrel)
venlafaxine (Effexor)

Monoamine Oxidase Inhibitors

phenelzine (Nardil)
tranylcypromine (Parnate)

Alpha/Beta Adrenergic Blocking

carvedilol (Coreg)
labetolol (Normodyne, Trandate)

Selective Serotonin Reuptake Inhibitors

fluoxetine (Prozac)
fluvoxamine (Luvox)
paroxetine (Paxil)
sertraline (Zoloft)

<==Anesthetic agents and their history

Toxicity and dosage==>