This document discusses vasoconstrictors which are drugs added to local anesthetics to prolong their duration and effectiveness. It classifies vasoconstrictors based on their chemical structure and mode of action. Epinephrine is described as the most commonly used vasoconstrictor due to its direct effects on alpha-1 and beta-2 receptors, which causes vasoconstriction and increased duration of anesthesia. Side effects are also discussed, noting the risks of hypertension, tachycardia and cardiac issues if overused. Maximum safe doses are provided for different local anesthetic solutions containing epinephrine or other vasoconstrictors like norepinephrine and phenylephrine.

1. ◦ Dr.RESHMA GAFOOR
DEPARTMENT OF ORAL AND MAXILLOFACIAL SURGERY
KMCT DENTAL COLLEGE

2. CONTENTS
1. Introduction
2. Classification
3. Function
4. Mode of action
5. Dilution of vasoconstrictors
6. Side effects
7. Pharmacology of specific agents
8. Conclusion
9. References

3. INTRODUCTION
Vasoconstrictors are the drugs that constricts the blood vessels and thereby control tissue
perfusion
They are added to LA to oppose the vasodilatory action of local anesthetic agent
They are Chemically identical or similar to Sympathetic nervous system mediators
-Epinephrine & Norepinephrine
Sympathomimetic or Adrenergic drugs

4. CLASSIFICATION
Based on presence or absence of Catechol group and Amine group
Catecholamines
Non
catecholamines

5. Catecholamines
Epinephrine Norepinephrine Levonordefrin Isoproterenol Dopamine

6. Non catecholamines
Amphetamine
Methamphetamine
Hydroxyamphetamine
Mephentermine
Methoxamine
Metaraminol
Ephedrine
Phenylephrine

7. Based on mode of action
Direct acting
• Act directly on
adrenergic
receptors
Indirect acting
• Acts by releasing
norepinephrine
from adrenergic
nerve terminals
Mixed acting
• Both directly on
receptors and
release of
norepinephrine

8. Direct
acting
Epinephrine
Norepinephrine
Dopamine
Phenylephrine
Indirect
acting
Tyramine
Amphetamine
Methamphetamine
Mixed
acting
Metaraminol
Ephedrine

9. What happens if you don’t use a vasoconstrictor ?
Plain local anesthetics are vasodilators in nature
• Blood vessels in the area dilate
• Increase absorption of the local anesthetic into the
cardiovascular system ( redistribution )
• Higher plasma levels increased risk of toxicity
• Decreased depth and duration of anesthesia diffusion
from site
• Increased bleeding due to increased blood perfusion to the area

10. MODE OF ACTION
Adrenergic receptors
• Found in most tissues of body
• Inhibitory or excitatory
• Receptors –Alpha1,Alpha2, β1, β2, β3
 Alpha1:- blood vessels in skin and genitourinary
system
Alpha2:-presynaptic nerve terminals
 Β 1:- heart and intestine
 Β 2:- bronchi, vascular bed, uterus
 Β3:- brown and white adipose tissue

11. ADRENORECEPTORS
• Vasoconstriction
• Increased peripheral resistance
• Increased blood pressure
• Mydriasis
• Increased closure of internal sphincter of
bladder
Alpha 1
• Inhibition of- Norepinephrine release
• - Acetyl choline release
• - Insulin release
Alpha 2

12. • Tachycardia
• Increased - Lipolysis
• - Myocardial contractility
• - Release of renin
Beta 1
• Vasodilation
• Slightly decreased peripheral resistance
• Bronchodilation
• Increased muscle and liver glycogenolysis
• Increased release of glucagon
• Relaxed uterine smooth muscle
Beta 2

13. Receptor stimulation
In blood vessels supplying skeletal muscles, vascular smooth muscle has both alpha 1 and beta2
adrenergic receptors

14. Release of catecholamines
• For indirectly acting drugs
• Amphetamine or tyramine
• Causing the release of the norepinephrine from storage sites in adrenergic nerve terminals
• Tachyphylaxis :
-Repeated doses of drug is less effective due to depletion of norepinephrine

15. DILUTION OF VASOCONSTRICTORS
The dilution of vasoconstrictors is commonly referred to as a ratio
( e.g : 1 to 1000 [written 1 : 1000])
Ratio of drug to carrier medium
1:1000 = 1 g in 1000 ml or 1000 mg in 1000 ml of solution
1:10,000 contains 0.1 mg/ml
1:100,000 contains 0.01 mg/ml

16. • 1:200,000 epinephrine contains 0.005 mg/mL epinephrine
- Provides comparable results with fewer systemic side effects
- Widely used and accepted in dentistry and medicine
• In 1903, Braun suggested using adrenalin as a chemical tourniquet to prolong the duration of local
anesthetics

17. Concentration of clinically used vasoconstrictors

18. SIDE EFFECTS
Unfortunately, the effects of vasoconstrictors are not always beneficial
The cardiac excitatory action of epinephrine, which is desired in the management
of medical emergencies such as anaphylaxis, may be detrimental to a patient with
reduced cardiovascular system reserve
Angina or myocardial infarction could conceivably result if the patient's
cardiovascular system is unable to respond to the demands caused by actions of
the vasoconstrictor

19. Epinephrine may indirectly cause central nervous system excitation, as well have
effects on metabolism and bronchial and gastrointestinal smooth muscle
Signs and symptoms of vasoconstrictor toxicity include hypertension, tachycardia,
tremors, headache, palpitations, and cardiac dysrhythmias
Drug interactions : Significant drug interactions may occur between
vasoconstrictors injected with local anesthetic agents and either tricyclic
antidepressants or β blockers

20. CONTRAINDICATIONS TO USING
VASOCONSTRICTORS
1. Blood pressure > 200/ 115 mm Hg
2. Severe cardiovascular disease ASA IV +
3. Acute myocardial infarction in the last 6 months
4. Anginal episodes at rest
5. Cardiac dysrhythmias that are refractory to drug treatment
6. Patient is in a hyperthyroid state of observable distress

21. 7. Levonordefrin and norepinephrine are absolutely contraindicated in patients taking tricyclic
antidepressants (elavil , sinequan )
8. Pheochromocytoma
9. Sulphite allergies
10. Patients receiving MAO inhibitors and phenothiazines
11. Diabetes

22. PHARMACOLOGY OF SPECIFIC AGENTS
Epinephrine
Norepinephrine (Levarterenol)
Levonordefrin
Phenylephrine Hydrochloride
Felypressin

23. EPINEPHRINE (Adrenalin)
• Synthetic
• Natural (80% of adrenal medulla
secretions)- levorotatory alkaloid
Source
• Nonselective adrenergic agonist,
stimulating α1-, α2-, β1- and β2-
adrenergic receptors
Mode of
action

24. CV
dynamics
Increased
systolic and
diastolic BP
due to alpha
receptor
response
Increased
Cardiac
Output -
Positive
chronotrop
ic action
Increased
stroke
volume &
heart rate
increased
Increased
strength of
contraction
- Positive
inotropic
action
Increased
myocardial
demand
for oxygen
Systemic effects

25. Pacemaker cells
• Beta 1- increased irritability of cells
• Increased dysrrythmias

26. Vasculature
• Beta 2 receptors dilation ,more sensitive
• Alpha 1 receptors constriction
• Small doses produce dilation the vessels as a
result of β2 actions
• Larger doses produce vasoconstriction because
α receptors are stimulated
Hemostasis
• High tissue concentrations of epinephrine in the
surgical site- Vasoconstriction -Predominant alpha
1 receptor action
• Beta receptors domination
- Reverts to dilation and increased bleeding
- Post op bleeding 6 hours after injection is
common

27. Respiratory System
•Potent dilator due to Beta 2 stimulation
•Bronchiolar smooth muscle relaxed
•Management of bronchospasm – status asthmaticus
CNS
• Not a potent CNS stimulant

28. Metabolism
• Epinephrine increases oxygen consumption in all tissues
• Beta stimulation – glycongenolysis in liver and skeletal muscle
• Elevates blood sugar

29. CLINICAL APPLICATIONS
Management of acute allergic reactions
Management of refractory bronchospasm (status asthmaticus)
Management of cardiac arrest
As a vasoconstrictor, for hemostasis
As a vasoconstrictor in local anesthetics to decrease absorption into the cardiovascular system
As a vasoconstrictor in local anesthetics to increase the depth of anesthesia
As a vasoconstrictor in local anesthetics to increase the duration of anesthesia
To produce mydriasis

30. MAXIMUM DOSE FOR DENTAL
APPOINTMENT
Normal healthy patient
0.2 mg per appointment
•Significant cardiovascular impairment
•0.04 mg per appointment (2 catridges of 1:1,00,000 epi )

31. 1.8 ml Catridge of 2 % Lidocaine 1:100,000 Epi
Maximum Epinephrine : 11 Catridges
Maximum Anesthetic : 300 mg
1.8 ml Catridge of 2 % Lidocaine 1:200,000 Epi
Maximum Epinephrine : 22 Catridges
Maximum Anesthetic : 300 mg

32. NOREPINEPHRINE (Levarterenol)
Mode of action
Acts predominantly on α-adrenergic receptors(90%) Also stimulates β actions in the heart (10%)
Natural form constitutes approximately 20% of the catecholamine production of the adrenal
medulla
Synthetic and natural forms
Source

33. • Nor epinephrine lacks Beta 2 actions and produce intense peripheral vasoconstriction with
possible dramatic elevations in blood pressure
• Side effect ratio is 9 times higher than epinephrine
• Its use in dentistry is not recommended and its use is diminishing

34. Systemic actions
Cardiovascular
Dynamics
• Increased systolic pressure
• Increased
diastolic pressure
• Decreased heart
rate
• Unchanged or slightly
decreased cardiac output • Increased stroke
volume
• Increased total peripheral
resistance

35. Respiratory system
• Produce α-induced constriction of lung arterioles, which reduces airway resistance to a small degree
CNS
• Not a potent CNS stimulant
Metabolism
• Increases basal metabolic rate
• Tissue oxygen consumption is also increased in the area of injection.
• Elevation in blood glucose levels

36. MAXIMUM DOSE FOR DENTAL
APPOINTMENT
Normal healthy patient
0.34 mg per appointment
10 mL of a 1:30,000 solution
•Significant cardiovascular impairment
•0.14 mg per appointment
•4 mL of a 1:30,000 solution

37. LEVONORDEFRIN
• Considered one-sixth as effective a vasopressor as epinephrine ; therefore used in high concentration (1:20,000)
• Obtained with mepivacaine in a 1:20,000 dilution.
•Mode of action though direct alpha (75%) and beta stimulation (25%)
• Levonordefrin produces less cardiac and CNS stimulation than is produced by epinephrine
• Maximum dose = 1 mg per appointment (11 catridges)

38. PHENYLEPHRINE HYDROCHLORIDE
• It is a vasoconstrictor in LA, for management of hypotension, as a nasal decongestant, and in
ophthalmic solutions to produce mydriasis
• Direct alpha stimulation (95%)
• No longer available In dental cartidges (was used along 4% procaine in 1:2500 dilution)
• Considered one twentieth as potent as epinephrine
• Excellent vasoconstrictor with few side effects

39. FELYPRESSIN (Citanest forte)
• Synthetic analogue of posterior pituitary hormone (Octapressin)
• Available as vasoconstrictor in combination with prilocaine
• Acts by directly stimulating vascular smooth muscle
• Actions more pronounced on venous than arteriolar microcirculation
•Can be safely used in patients with hypertension (safe dose 0.18 IU/ml)
• Has little effect on heart or on adrenergic nerve transmission
• Less potent than the catecholamines

40. • Can be safely administered to hyperthyroid patients and anyone receiving MAO
Inhibitors or tricyclic antidepressants.
• It has wide margin of safety and the incidence of systemic reaction is minimal
• Maximum dose =0.27 IU

41. TERMINATION OF ACTION AND DRUG
INTERACTION
By reuptake –reuptake is blocked but tricyclic antidepressants leading to prolonged duration of
action
By deactivation by extraneuronal enzymes ie catechol – o -methyl transferase
•Epinephrine to metanephrine and nor epinephrine to nor metanephrine
•Uptake by blood stream
Intraneuronal enzyme destruction
•By monoamine oxidase to dihydroxymandelic acid
•Action by both COMT and MAO -VANILLYLMANDELIC ACID

42. SELECTION OF VASOCONSRTICTOR
Factors
considered
Length of the
dental
procedure
Need for
hemostasis
during and after
the procedure
Requirement
for
postoperative
pain control
Medical status
of the patient.

43. Length of procedure
•Pulpal and hard tissue anesthesia with 2% lidocaine lasts approximately 10 minutes
•Addition of 1:50,000, 1:80,000, 1:100,000, or 1:200,000 epinephrine increases this to approximately
60 minutes
•Prilocaine 4%
-nerve block injection, provides pulpal anesthesia of about 40 to 60 minutes duration
-Infiltration injection provides approximately 10 to 15 minutes of pulpal anesthesia
•The addition of a 1:200,000 epinephrine concentration to prilocaine increases this slightly to about
60 to 90 minutes

44. Requirement for Hemostasis
• Epinephrine is effective in preventing or minimizing blood loss during surgical procedures However,
epinephrine also produces a rebound vasodilatory effect as the tissue level of epinephrine declines
• This leads to possible bleeding postoperatively, which potentially interferes with wound healing and
could compromise a patient's cardiovascular status
• Epinephrine produces a definite rebound β effect once α-induced vasoconstriction has ceased

45. • Phenylephrine a longer-acting, almost pure α-stimulating vasoconstrictor, does not produce a
rebound β effect because its β actions are minimal
• It is not as potent a vasoconstrictor as epinephrine, hemostasis during the procedure is not as
effective
• Norepinephrine is a potent α stimulator and vasoconstrictor that has produced documented cases
of tissue necrosis and sloughing
• Norepinephrine cannot be recommended as a vasoconstrictor in dentistry because its
disadvantages outweigh its advantages
• Felypressin constricts the venous circulation more than the arteriolar circulation and therefore is
of minimal value for hemostasis

46. Medical Status of the Patient

47. Hypertensive patients
• Local anesthetic solutions with vasoconstrictors are not contraindicated in hypertensive
patients, due to their hemodynamic effects, local anesthetics without vasoconstrictors are
mainly preferred by the clinicians
• Life-threatening complications due to the sudden and dramatic increase in blood pressure can
occur during dental procedures in hypertensive patients
• Use of anesthetic solutions without vasoconstrictors increase the risk of hypertensive crisis due
to the potential pain caused by insufficient intraoperative anesthesia
Ezmek, Bahadir, Ahmet Arslan, Cagri Delilbasi, and Kemal Sencift. "Comparison of Hemodynamic Effects of Lidocaine,
Prilocaine and Mepivacaine Solutions without Vasoconstrictor in Hypertensive Patients." Journal of Applied Oral Science
18.4 (2010): 354-59

48. Pheochromocytoma
•The presence of pheochromocytoma (a tumor involving cells that produce catecholamines) is an
absolute contraindication to the use of epinephrine
•Patients who have this disease may have an over- production of endogenous epinephrine or
norepinephrine
•A sympathetic response to the increased level of circulating catecholamines results in the
common manifestations of headache , excessive perspiration and palpitations in 75% of these
cases
•Due to the excessively high levels of circulating catecholamines already present, exogenous
epinephrine in local anesthetics could only have adverse effects and might precipitate a crisis.

49. Thyrotoxicosis
• Contraindication for the use of vasoconstrictors in local anesthesia.
• Thyrotoxicosis may be present in patients with primary or secondary hyperthyroidism
• The clinical manifestations of thyrotoxicosis include increased heart rate and systolic blood
pressure, marked irritability , fine tremor and elevated body temperature
• Thyroid storm can be precipitated by exogenously administered sympathomimetic amines
• Thyroid storm hypertension , delirium and eventually vasomotor collapse can result
• The mortality rate associated with this acute crisis can be as high as 70%

50. Drug interactions
Inhalation Anesthetics
• Some general anesthetics sensitize the myocardium to the direct myocardial effects of
sympathomimetic amines including epinephrine
• Halothane possess the lowest arrythmogenic threshold for epinephrine
• Enflurane and isoflurane have a minimal effect on myocardial sensitivity to sympathomimetics
• Several investigators has showed that epinephrine-halothane induced arrythmias are more likely to
be longer duration and more numerous than those occurring with enflurane or isoflurane
• Maximum dose with halothane is 0.1 mg in 10 minutes to 0.3 mg in 60 minutes

51. • Epinephrine impregnated retraction cord utilized in restorative dentistry to minimize bleeding during
impression making has been observed to provoke cardiac dysrhythmias during halothane anesthesia
• An inch of cord contains the equivalent of 0.22 to 0.30 mg of L-epinephrine in 8 % racemic
epinephrine retraction cords, approximately equal to the amount of epinephrine contained in twelve
cartridges of dental anesthetic with 1:100,000 epinephrine

52. Antidepressants
Two classes of antidepressant drugs are tricyclic agents and monoamine oxidase (MAO)
inhibitors
TCA prevents the neuronal uptake of catecholamines at the adrenergic nerve terminals
This results in higher concentration of vasoconstrictor at the sympathomimetic neuroeffector
junction

53. Beta blockers
• The beta blocking agents commonly used in the treatment of hypertension may interact with
epinephrine to enhance its vasopressor action
• If a nonselective b-blocker such as propranolol is used and significant systemic absorption of
epinephrine occurs, the beta 1,beta2 vasodilatory effects of epinephrine will be blocked,
allowing the a vasoconstrictive effects to function unopposed
• Resulting in an increase in systolic and diastolic blood pressure, and a compensatory reflex
bradycardia

54. Phenothiazines
• This class of drug is used largely for its antiemetic, tranquilizing and anti-psychotic effects
• Common to phenothiazine toxicity is the presence of arterial hypotension caused by the
blockage of alpha adrenergic receptors in the peripheral vasculature
• Treatment of such hypotension with epinephrine may have disastrous results as the
vasoconstricting (alphaadrenergic) property of the epinephrine is partially blocked by the
phenothiazine, but the vasodilating effect remains the same leading to worsening
hypotension

55. Phentolamine Mesylate in Reversal Local
Anesthesia
Phentolamine mesylate under the trade name of OraVerse
First therapeutic agent approved and marketed for the soft tissue anesthesia reversal and the
associated functional deficits due to intraoral submucosal injection of an LA consisting of a
vasoconstrictor
Dosage form of OraVerse is 0.4 mg/1.7 ml solution per cartridge
The suggested dose of OraVerse is on the basis of the number of cartridges of LA with
vasoconstrictor administered. It is administered in an equal volume, up to a maximum of 2
cartridges

56. OraVerse is administered at the same location and by the same technique(nerve block or
infiltration) used previously for the LA administration
The maximum dose of OraVerse recommended in pediatric patients weighing 15-30 kg is 1/2
cartridge (0.2mg)
OraVerse is contraindicated for use in children weighing less than 15 kg (33 lbs) or less than 6
years of age
Yagiela, John A. “What's new with phentolamine mesylate: a reversal agent for local anaesthesia?.” SAAD
digest vol. 27 (2011): 3-7

57. CONCLUSION
The use of local anesthetics with vasoconstrictors is safe in patients with cardiovascular
compromise and on controlled diabetes patients as long as a proper anesthetic technique is
performed (avoiding intravascular technique) the dose used is not higher than 5.4 ml (equivalent
to 3 vials of anesthetics with 1:100000 epinephrine) and the behavioural management of the
patient and the analgesia maintaince during the treatment are adequate.

58. REFERENCES
1. Malamed S. Handbook of local anesthesia 7th edition
2. Bennett C. Monheim's local anesthesia and pain control in dental practice
3. Ezmek, Bahadir, Ahmet Arslan, Cagri Delilbasi, and Kemal Sencift. "Comparison of
Hemodynamic Effects of Lidocaine, Prilocaine and Mepivacaine Solutions without
Vasoconstrictor in Hypertensive Patients." Journal of Applied Oral Science 18.4 (2010): 354-59

59. 5. Yagiela, John A. “What's new with phentolamine mesylate: a reversal agent for local
anaesthesia?.” SAAD digest vol. 27 (2011): 3-7
6. Balakrishnan R, Ebenezer V. Contraindications of vasoconstrictors in Dentistry. Vol. 6,
Biomedical and Pharmacology Journal. 2013. p. 409-14