Pharmacology of Local Anesthetics and Vasoconstrictors

Question 1

1. Name the two major classifications of local anesthetic agents:
   a. lidocaine and epinephrine
   b. injectable and infiltratable
   c. amides and esters

Answer 1

c. amides and esters

Question 2

2. Which of the following is true of the ester classification of local anesthetic agents?
   a. the primary by-product of the metabolism of esters is methemoglobinemia
   b. esters are metabolized in the plasma by the enzyme pseudocholinesterase
   c. some metabolism of esters can occur in the lungs
   d. examples of esters include Lidocaine 2% and Bupivacaine 0.5%

Answer 2

b. esters are metabolized in the plasma by the enzyme pseudocholinesterase

Esters are metabolized in the plasma by the enzyme pseudocholinesterase, while the primary site of biotransformation of amides is in the liver.

The other characteristics which were listed are true of the amide classification of local anesthetic agents:

the primary by-product of the metabolism of amides is methemoglobinemia (because of this, amides are contraindicated for people with atypical methemoglobinemia – they are unable to metabolize amides properly)
some metabolism of amides (specificially prilocaine) can occur in the lungs
examples of amides include Lidocaine 2% and Bupivacaine 0.5%

Question 3

3. Generally speaking, the effect that most local anesthetic agents have on the vascular bed is:
   a. vasodilating
   b. vasoconstricting
   c. they have no effect

Answer 3

a. vasodilating

Most local anesthetic agents have a vasodilating effect on the vascular bed. This degree of vasodilation can vary between local anesthetic agents.

Question 4

4. Generally speaking, which classification of local anesthetic agents is the MOST vasodilating?
   a. amides
   b. esters
   c. neither - they are both equally vasodilating

Answer 4

b. esters

Esters are potent vasodilating agents, and more vasodilating than amides.

Question 5

5. What are the important clinical effects of vasodilation of local anesthetics?
   a. it will increase the rate of absorption of the local anesthetic agent into the blood
   b. it will decrease the duration of pain control of the local anesthetic agent
   c. it will increase the level of local anesthetic in the blood
   d. it will increase the potential for overdose
   e. all of the above

Answer 5

e. all of the above

Question 6

6. Local anesthetic agents readily cross the placenta and can then enter the circulatory system of the fetus.
   a. That statement is true
   b. That statement is false

Answer 6

a. That statement is true

Question 7

7. If the use of a certain local anesthetic agent is absolutely contraindicated for a patient, this means:
   a. under no circumstances should this agent be administered to the patient due to the risk of a potentially toxic or lethal reaction
   b. the agent may be administered to the patient after considering the risks and benefits from its use and if an alternative agent is not available
   c. there is no risk whatsoever from the use of this local anesthetic agent

Answer 7

a. under no circumstances should this agent be administered to the patient due to the risk of a potentially toxic or lethal reaction

Question 8

8. The allergic reactions that occur from the use of esters are due to:
   a. the type of ester that is used
   b. the type of topical anesthetic that was used prior to injection
   c. the degree of vasodilation of the ester that was used
   d. the metabolic by-product of esters

Answer 8

d. the metabolic by-product of esters

Question 9

9. Explain what the term “half-life” means in relation to a local anesthetic agent:
   a. the time it takes for the local anesthetic to reach half its potential effect on the patient
   b. the time it takes for the local anesthetic in the cartridge to lose half its potency
   c. the time required for a 50% reduction of the local anesthetic agent in the patient’s blood level
   d. the time required for the patient to lose 50% of the sensation in the targeted area

Answer 9

c. the time required for a 50% reduction of the local anesthetic agent in the patient’s blood level

The term “half-life” refers to the time required for a 50% reduction of the local anesthetic agent in the patient’s blood level.

The clinical significance of this is that agents with the shortest half-lives are the least toxic (in normal, healthy adults). For example, the half-life of lidocaine in a normal, healthy adult is 1.8 hours. The half-life of procaine is 0.1 hour. Therefore, procaine would be less toxic.

On the other hand, the half-life of lidocaine in an adult with hepatic dysfunction is 4.9 hours. Compare this to the 1.8 hours for a healthy adult with no medical complications.

Question 10

10. What type of effect do local anesthetics have on the central nervous system (CNS)?
    a. they excite the CNS
    b. they depress the CNS
    c. they have no effect on the CNS

Answer 10

b. they depress the CNS

Local anesthetics depress the CNS. However, at low blood levels there are not any significant CNS effects.

Effects are directly related to the blood or plasma level of the local anesthetic. The higher the level in the blood or plasma, the greater the clinical action.

Question 11

11. Vasoconstrictors are added to local anesthetics for which of the following reasons:
    a. to counteract the vasodilating effects of the local anesthetic agent
    b. to increase the blood flow to the site of the injection
    c. to prolong vasodilation
    d. to increase the rate at which the local anesthetic is absorbed into the cardiovascular system

Answer 11

a. to counteract the vasodilating effects of the local anesthetic agent

Vasoconstrictors will counteract the vasodilating effects of the local anesthetic agent. You will recall that most local anesthetic agents have a vasodilating effect on the vascular bed. You will also recall that when vasodilation occurs, it increases the rate of absorption of the local anesthetic into the blood, which will:

consequently decrease the duration of pain control due to quicker diffusion of the local anesthetic out of the vessel, which will:
subsequently increase the level of the local anesthetic in the blood, which can:
increase the potential for an overdose
Additionally, the increased blood flow at the site can cause increased bleeding at the site the local anesthesia was administered. Therefore, a vasoconstrictor is needed to counteract these effects.

Question 12

12. The role of vasoconstrictors is to:
    a. decrease hemostasis
    b. reduce allergic reactions
    c. increase metabolism of the local anesthetic agent
    d. constrict blood vessels, thereby decreasing the blood flow to the site of injection

Answer 12

d. constrict blood vessels, thereby decreasing the blood flow to the site of injection

Vasoconstrictors will constrict blood vessels, thereby decreasing the blood flow to the site of injection.

The consequence of this is that absorption of the local anesthetic agent into the cardiovascular system will be slowed down. This is favorable because there will be lower anesthetic blood levels which will decrease the risk of local anesthetic toxicity.

Also, decreased blood flow at the site of administration is useful when a dental/dental hygiene procedure may create increased bleeding.

Question 13

13. Vasoconstrictors will allow higher volumes of the local anesthetic to remain in and around the nerve for shorter periods of time which will decrease the duration of action of the local anesthetic agent.
    a. This statement is true
    b. This statement is false

Answer 13

b. This statement is false

Vasoconstrictors will allow higher volumes of the local anesthetic to remain in and around the nerve for LONGER periods of time which will INCREASE the duration of action of the local anesthetic agent.

Question 14

14. While esters are more vasodilating than amides, there is one ester which is an exception and produces vasoconstriction. This drug is:
    a. procaine
    b. cocaine
    c. lidocaine
    d. mepivacaine

Answer 14

b. cocaine

Cocaine consistently elicits vasoconstriction. It is also the only naturally occurring local anesthetic.

While cocaine initially produces vasodilation, that is transient and is followed by an intense and prolonged vasoconstriction. Presently, cocaine is considered to be more of a drug of abuse than a therapeutic drug.

Because of cocaine’s strong vasoconstriction properties, local anesthetics containing vasopressors should be avoided in patients who have used cocaine on the day of their dental appointment.

Question 15

15. Local anesthetics are absorbed readily when applied topically to intact skin.
    a. This statement is true
    b. This statement is false

Answer 15

b. This statement is false

Local anesthetics are absorbed topically through mucous membranes, not skin. Rapid uptake occurs in the tracheal mucosa, with slower uptake in the pharyngeal mucosa. Uptake is even slower in the esophageal or bladder mucosa.

Question 16

16. Factors that influence the blood level of a local anesthetic agent after it has been injected include:
    a. the health status of the individual
    b. the rate that the drug is absorbed into the cardiovascular system
    c. the amount of food the individual has eaten in the past 12 hours
    d. a and b
    e. a, b and c

Answer 16

d. a and b

The answers were a and b: the health status of the individual and the rate that the drug is absorbed into the cardiovascular system influence the blood level of a local anesthetic agent after it has been injected.

If the individual is medically compromised, (as in congestive heart failure) the rate of distribution of the local anesthetic agent will be slower. If they are healthy, absorption will be quicker, resulting in lower blood levels.

Question 17

17. The metabolic by-product responsible for allergic reactions to the ester classification of anesthetics is:
    a. pseudocholinesterase
    b. para-aminobenzoic acid
    c. propylalanine

Answer 17

b. para-aminobenzoic acid

The correct answer is para-aminobenzoic acid, also known as PABA.

Allergic reactions that can occur from the administration of the ester classification of anesthetics is from the PABA that is the metabolic by-product of the drug. The reaction is not from the use of the local anesthetic agent itself (for instance, the use of the parent compound procaine).

Question 18

18. The primary excretory organ for a local anesthetic agent and its metabolic products is the:
    a. liver
    b. kidney
    c. lungs
    d. intestinal tract

Answer 18

b. kidney

The answer is the kidney. Depending on the local anesthetic agent used, a portion of the agent will be excreted unchanged in the urine.

Question 19

19. Why would significant renal impairment be a relative contraindication to the use of ester and amide type anesthetics?
    a. it could lead to an allergic reaction
    b. it will increase the vasodilating effect of the local anesthetic agent
    c. it could cause slightly elevated blood levels and an increased potential for toxicity
    d. renal impairment is not a relative contraindication to the use of either esters or amides

Answer 19

c. it could cause slightly elevated blood levels and an increased potential for toxicity

Significant renal impairment, as seen with chronic glomerulonephritis and/or pyelonephritis or for those patients undergoing renal dialysis, is a relative contraindication to the use of either esters or amides.

If a case poses a relative contraindication, it is preferable to avoid administering the drug in question since it can lead to an adverse response. If an acceptable alternative is available, that is the drug of choice. But if there is no acceptable alternative, then the drug in question may be used. Caution should be exercised and the minimal dose should be administered to the patient.

Question 20

20. Which two body systems are very susceptible to the action of local anesthetic agents?
    a. the digestive system and the respiratory system
    b. the digestive system and the central nervous system
    c. the central nervous system and the digestive system
    d. the cardiovascular system and the central nervous system

Answer 20

d. the cardiovascular system and the central nervous system

Question 21

21. What is the brand (proprietary) name for the vasoconstrictor, epinephrine?
    a. Adrenalin
    b. Octapressin
    c. Noradrenalin
    d. Lidocaine

Answer 21

a. Adrenalin

The brand (proprietary) name for epinephrine is Adrenalin.

Of the other 3 choices:

Octapressin is the brand name for another vasoconstrictor called Felypressin (not available in the U.S.)
Noradrenalin is a brand name for Norepinephrine (not available in the U.S.)
Lidocaine is not a vasoconstrictor - it is a local anesthetic agent.

Question 22

22. In the usual therapeutic doses given in a dental setting, epinephrine is a potent central nervous system stimulant.
    a. True
    b. False

Answer 22

b. False

In the usual therapeutic doses given in a dental setting, epinephrine is NOT a potent central nervous system stimulant. The clinician will see prominent CNS-stimulating actions only when an excessive dose is administered.

Epinephrine can be found in the amide Lidocaine 2% in concentrations of 1:50,000, 1:100,000 or 1:200,000. It is also found in the following amides:

Prilocaine 4% (Citanest Forte) in a concentration of 1:200,000
Bupivacaine 0.5% (Marcaine) in a concentration of 1:200,000
Articaine 4% (Septocaine) in a concentration of 1:100,000
Mepivacaine 2% (Carbocaine) in a concentration of 1:200,000
In contrast, epinephrine is used IM 1:1,000 to treat anaphylaxis, and IV 1:10,000 to treat cardiac arrest.

Question 23

23. What is the brand (proprietary) name for the vasoconstrictor, levonordefrin:
    a. Neo-Cobefrin
    b. Norepinephrine
    c. Bupivacaine
    d. Oraqix

Answer 23

a. Neo-Cobefrin

Neo-Cobefrin is the brand (proprietary) name for the vasoconstrictor, levonordefrin.

For the other three choices

Norepinephrine is a vasoconstrictor that is no longer available in the U.S.
Bupivacaine is a local anesthetic agent - not a vasoconstrictor
Oraqix is also not a vasoconstrictor - it is a topical anesthetic.

Question 24

24. Amides are biotransformed primarily in the:
    a. lungs
    b. kidney
    c. liver
    d. urinary tract
    e. intestinal tract

Answer 24

c. liver

Amides are biotransformed primarily in the liver. For this reason, large doses of amides should be avoided in patients with liver dysfunction.

The amide Prilocaine (Citanest), is biotransformed primarily in the liver, with some possibly occurring in the lungs.

Question 25

25. Esters are biotransformed primarily in the:
    a. liver
    b. plasma
    c. intestinal tract
    d. kidney

Answer 25

b. plasma

Esters are biotransformed primarily in the plasma. They are hydrolyzed by the enzyme pseudocholinesterase.

There is concern in patients with an atypical form of pseudocholinesterase, found in 1 out of every 2,800 people. These individuals cannot hydrolyze esters and consequently administration of an ester to these patients will result in higher blood levels of the ester for a longer period of time with an increased potential for toxicity.

Currently, esters are available for use primarily in topical anesthetics.

Question 26

26. A new patient’s medical history indicates that the use of a vasoconstrictor is absolutely contraindicated. On the day of her appointment, she is to receive scaling and root planing on her mandibular right quadrant, accompanied by an IAN, lingual and long buccal injection.
    You anticipate that it will take you approximately 1 hour to complete this dental hygiene therapy. Which of the following anesthetic agents would be the correct one to use?

a. Marcaine
b. Citanest Plain
c. Citanest Forte
d. Xylocaine

Answer 26

b. Citanest Plain

The best choice would be Citanest Plain as it does not contain epinephrine and provides from 2 - 4 hours of soft tissue anesthesia when used for regional blocks. When used for infiltration, Citanest Plain provides 1.5-2 hours of soft tissue anesthesia.

Citanest Forte and Marcaine each contain a 1:200,000 concentration of epinephrine, which was contraindicated for this patient. However, this is a lower concentration than found in, for example, Lidocaine 2% with 1:100,000 epinephrine (Xylocaine).

Question 27

27. A patient has received the IAN, lingual and long buccal injections for dental hygiene therapy in the mandibular right quadrant. The procedure has taken longer than expected and the patient is experiencing pain in the area. The injections are repeated, however, this time patient still expresses that the area remains sensitive.
    What is the name given to this clinical situation?

a. reverse order
b. tachyphylaxis
c. drug depression
d. impulse conduction

Answer 27

b. tachyphylaxis

This situation is referred to as tachyphylaxis. It is an increasing tolerance to a drug that is administered repeatedly.

Tachyphylaxis is more likely to occur if the patient’s nerve function is allowed to return prior to reinjection. To avoid this from occurring to a patient:

reinject as, or before, your patient expresses the first sign of feeling
use a longer-acting anesthetic if you know ahead of time that you’ll be working a longer than average time on your patient

Question 28

28. Your patient has just received an injection of Marcaine and informs you that there was a burning sensation during the injection. This is due to:
    a. the presence of the vasoconstrictor
    b. the presence of infection at the site of injection
    c. the anesthetic solution is excessively cold
    d. the solution was administered too quickly

Answer 28

a. the presence of the vasoconstrictor

Question 29

29. In the previous question, the reason the presence of a vasoconstrictor caused a burning sensation is because the vasoconstrictor:
    a. increased the pH of the solution in the cartridge
    b. lowered the pH of the solution in the cartridge
    c. rendered the solution in the cartridge neutral
    d. lowered the pH of the tissues surrounding the injection site

Answer 29

b. lowered the pH of the solution in the cartridge

The vasoconstrictor lowered the pH of the solution in the cartridge down to 3.3 - 4.0, thus making it more acidic and more likely to create a burning sensation upon injection.

When a vasoconstrictor is present in an anesthetic solution, the preservative sodium bisulfite is frequently used to prevent the deterioration of the vasoconstrictor by oxygen. If oxygen is present in the cartridge, the sodium bisulfite will react with it before it can destroy the vasoconstrictor. This creates sodium bisulfate that has an even lower pH and will cause the burning sensation.

To avoid this from occurring, use only fresh cartridges - avoid using older cartridges when using a vasoconstrictor.

Question 30

30. Factors to be considered when selecting a local anesthetic agent for your patients include:
31. the length of time that you anticipate you will require pain control for your patient
32. the potential for your patient to have discomfort during the post-treatment time frame
33. the possibility that your patient may accidentally self-mutilate themselves while numb
34. determining whether hemostasis will be needed during your dental/dental hygiene procedures
35. the medical status of the patient

a. all of the above
b. none of the above
c. 1, 2, 3 and 4 only
d. 2, 3, 4 and 5 only
e. 2, 4 and 5 only

Answer 30

a. all of the above

the length of time that you anticipate you will require pain control for your patient
In other words, should you use Marcaine which provides 4 - 9 hours of soft tissue anesthesia, or should you use Citanest Plain which provides 1.5 - 2 hours of anesthesia?
the potential for your patient to have discomfort during the post-treatment time frame
Are you doing extensive work that will leave your patient very uncomfortable for several hours post-treatment? If so, perhaps you should use Marcaine. This will allow the patient to have minimal discomfort for numerous hours post-treatment.
the possibility that your patient may accidentally self-mutilate themselves while numb
Is your patient a child, mentally challenged or any other type of patient that may not understand that they need to be careful immediately following treatment to avoid biting their lip or cheek? For this instance, a short-acting anesthetic would be in order.
determining whether hemostasis will be needed during your dental/dental hygiene procedures
Will you need a vasoconstrictor to help reduce bleeding in the area where you will be working?
the medical status of the patient
Does the patient’s medical history contraindicate the use of a vasoconstrictor? Does the patient have any other condition that may contraindicate the use of a specific local anesthetic?

Question 31

31. Epinephrine stimulates glycogenesis in the liver and skeletal muscles, producing an elevation of blood glucose levels.
    a. This statement is true.
    b. This statement is false.

Answer 31

a. This statement is true.

This statement is true, although at least 4 cartridges of anesthetic containing 1:100,000 epinephrine must be administered to elicit this response. For this reason, epinephrine-containing anesthetics must be used judiciously with diabetic patients.

Question 32

32. Levonordefrin is the vasoconstrictor of choice for patients taking tricyclic antidepressants (such as Elavil), BECAUSE TCAs do not effect the cardiovascular effects of levonordefrin.
    a. Both statement and reason are true
    b. Both statement and reason are false
    c. The statement is true, but the reason is false
    d. The statement is false, but the reason is true

Answer 32

Levonordefrin should be avoided in patients taking TCAs because the TCAs can enhance the cardiovascular activity 5- to 10-fold when combined with this vasopressor. Epinephrine combined with TCA’s can also increase activity by 2-fold. Thus, even epinephrine should be used with caution and in limited amounts in these cases.

Question 33

33. Epinephrine should be avoided with patients who have a history of thyroid disease, but who are now controlled with medication or surgery, BECAUSE they respond in an exaggerated manner to vasocontrictors.
    a. Both statement and reason are true
    b. Both statement and reason are false
    c. The statement is true, but the reason is false
    d. The statement is false, but the reason is true

Answer 33

b. Both statement and reason are false

Patients with surgically corrected or medication-controlled hyper- or hypo-thyroid conditions respond in a normal manner to epinephrine. Patients with uncontrolled hyperthyroid, however, may show an exaggerated response to vasoconstrictors. They may be used, but in limited amounts and with caution.