Pharmacology of

Vasoconstrictors
Semua anestetik local vasodilator: Procain paling
kuat. Prilocain dan mepicaine paling lemah.
Setelah injeksi anestetik local akan terjadi dilatasi
pembuluh darah
1. An increased rate of absorption of the local
anesthetic into the cardiovascular system, which in
turn removes it from the injection site
(redistribution)
2 Higher plasma levels of the local anesthetic, with
an attendant increase in the risk of local anesthetic
toxicity (overdose)
3 Decrease in both the depth and duration of
anesthesia because the local anesthetic diffuses away
from the injection site more rapidly
4 Increased bleeding at the site of treatment
 What happens if you dont use a vasoconstrictor?
*Plain local anesthetics are vasodilators by nature

1) Blood vessels in the area dilate

2) Increase absorption of the local anesthetic into the
cardiovascular system (redistribution)
3) Higher plasma levels increased risk of toxicity
4) Decreased depth and duration of anesthesia diffusion
from site
5) Increased bleeding due to increased blood perfusion to the
area
1) Patient is not numb as long without
epinephrine

2) Patient is simply not as numb

3) More anesthetic goes into the circulation

4) Increased bleeding; more blood to area

 Vasoconstrictors
Adrenergic drugs and are called
sympathomimetic, or adrenergic drugs

1) Constrict blood vessels decrease blood flow to the surgical site

2) Cardiovascular absorption is slowed lower anesthetic blood levels

3) Local anesthetic blood levels are lowered lower risk of toxicity

4) Local anesthetic remains around the nerve for longer periods

increased duration of anesthesia

5) Decreases bleeding
 Chemical Structure
Classification of Adrenergic Drugs
Classification by chemical structure is related to the
presence or absence of a catechol nucleus
Catechol is orthodihydroxybenezene
Sympathomimetic drugs that have a hydroxy (OH-)
substitution in the 3rd and 4th positions of the aromatic ring
are termed catechols
 Catecholamines
If the 3rd and 4th positions contain an amine group (NH2) attached to
the aliphatic side chain, they are then called catecholamines

Epinephrine
Norepinephrine natural catecholamines of sympathetic NS
Dopamine

Isoproterenol
and synthetic catecholamine
Levonordefrin
 Chemical Structure
Catecholamines Noncatecholamines
*Epinephrine Amphetamine
*Norepinephrine Methamphetamine
*Levonordefrin Ephedrine
Isoproterenol Mephentermine
Dopamine Hydroxyamphetamine
Metaraminol
Methoxamine
Phenylephrine
 Modes of Action
3 Classes of Sympathomimetic Amines:
1)*Direct Acting directly on adrenergic receptors
2) Indirect Acting use norepinephrine release
3) Mixed Acting both direct and indirect actions
2 Types of Adrenergic Receptors:
1) Alpha
-contraction of smooth muscle in blood vessels
-vasoconstriction
-Alpha 1 excitatory; post-synaptic
-Alpha 2 inhibitory; post-synaptic

2) Beta
-smooth muscle relaxation
-vasodilation/bronchodilation
-cardiac stimulation, i.e., increased
rate and strength of contraction
2 Types of Beta Receptors:

1) Beta 1
-found in heart and small intestines
-produces cardiac stimulation and lipolysis

2) Beta 2
-found in bronchi of the lung, vascular beds
and uterus
-produces bronchodilation and vasodilation
The dilution of vasoconstrictors is commonly referred to as a
ratio i.e., 1:50,000; 1:100,000; 1:200,000 etc,

A concentration of 1:1,000 means that there is 1 gram

(1000 mg) of solute (drug) contained in 1000 ml (1 L) of
solution, therefore, 1:1,000 dilution contains 1000 mg
in 1000 ml or 1.0 mg/ml of solution (1000 ug/ml)

The concentration of 1:1,000 is very concentrated

(strong); a much more dilute form is used in dentistry
for example, 1:50,000 > 1:100,000 > 1:200,000
(1:100,000 = 0.01 mg/1 ml of solution)
Norepinephrine
 NOREPINEPHRINE
Norepinephrine lacks Beta 2 actions (bronchodilation and
vasodilation) and produces intense peripheral vasoconstriction
with possible dramatic elevations in blood pressure

Norepinephrines side effect ratio is 9 times higher than

epinephrine

Norepinephrines use in dentistry is not recommended and its

use is diminishing around the world

Epinephrine remains the vasopressor of choice in dentistry

*Norepinephrine is not used because of its many side effects

Epinephrine
 Epinephrine
Sodium Bisulfite antioxidant added
18 months shelf life
Acts directly on Alpha and Beta receptors
Beta effects predominate
Increases force / rate of contraction
Increases stroke volume
Increases myocardial O2 use
Increases cardiac output / heart rate
Increases dysrhythmias and PVCs
Increases coronary artery perfusion
Increases systolic blood pressure
Decrease in cardiac efficiency
 Alpha receptor stimulation leads to hemostasis initially

Beta 2 actions predominate leading to vasodilation 6 hours after

a surgical procedure

Potent bronchodilator (asthma)

Not a potent CNS stimulant

Increases oxygen consumption in all tissues of the body

Reuptake by adrenergic nerves terminates epinephrine action

Ventricular fibrillation is possible

 Clinical Applications of Epinephrine
1) Management of acute allergic reactions
2) Management of bronchospasm
3) Management of cardiac arrest
4) Vasoconstrictor for hemostasis
5) Vasoconstrictor to decrease absorption into CVS
6) Vasoconstrictor to increase depth of anesthesia
7) Vasoconstrictor to increase duration of anesthesia
8) To produce mydriasis (excessive pupil dilation)
Levonordefrin
 Levonordefrin is freely soluble in dilute acid
solutions

Sodium bisulfite is added to delay its deterioration

Synthetic vasoconstrictor

Acts through direct Alpha receptor stimulation

(75%)

Acts through some Beta activity (25%)

 Levonordefrin produces less cardiac and CNS stimulation
than epinephrine

Levonordefrin is eliminated via COMT (catechol-O-methyl

transferase) and MAO (monamine oxidase)

Levonordefrin is obtained via Mepivacaine 1:20,000; used at

a higher concentration, i.e., 1:20,000 because it is
1/6th as potent as epinephrine

Levonordefrin has a maximum recommended dose of 11

cartridges
 -Levonordefrin is only 1/6th as strong as
Epinephrine, therefore, using a ratio of
1:20,000 Levonordefrin is like using a ratio of
1:120,000 of Epinephrine

-you will need more Levonordefrin because it is

only 15% as effective as Epinephrine
 Selection of a vasoconstrictor depends on:
1) Length of the dental procedure
2) Requirement for hemostasis
3) Requirement for post-operative pain control
4) Medical status of the patient
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

7) Levonordefrin and Norepinephrine are absolutely

contraindicated in patients taking tricyclic antidepressants
(Elavil, Sinequan)
 References
Malamed, Stanley: Handbook of Local Anesthesia. 5th Edition. Mosby. 2004