Transcript Pharmacology of Vasoconstrictors

Pharmacology of
Vasoconstrictors
What happens if you don’t 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
Why You Need Vasoconstrictors
Vasoconstrictors resemble 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
Dopamine
natural catecholamines of sympathetic NS
Isoproterenol
and
Levonordefrin
synthetic catecholamine
Chemical Structure
Catecholamines
*Epinephrine
*Norepinephrine
*Levonordefrin
Isoproterenol
Dopamine
Noncatecholamines
Amphetamine
Methamphetamine
Ephedrine
Mephentermine
Hydroxyamphetamine
Metaraminol
Methoxamine
Phenylephrine
Felypressin  synthetic analogue of vasopressin (ADH); not in U.S.
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)
per 1.8 ml cartridge of anesthetic
1:50,000
1:100,000
1:200,000
.036 mg epinephrine
.018 mg epinephrine
.009 mg epinephrine
decreasing potency of epinephrine
1:50,000 epinephrine is used to stop bleeding in a
surgical area; this amount of epinephrine is not used
for block anesthesia
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2)
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5)
Bleeding areas that require resin from any trauma
Nick the papilla with a bur; resin or alloy
Oral surgery root tip removal; bloody socket
Works awesome for short period of time
Use as alternative to electrosurgery unit
 Resting plasma epinephrine levels are doubled when one cartridge of
2% Lidocaine 1:100,000 epinephrine is injected
 Recent evidence suggests that epinephrine plasma levels equivalent to
those achieved during moderate to heavy exercise occur after intraoral
injection
 Moderate increase in cardiac output and stroke volume occurs
 Blood pressure and heart rate are minimally affected
 IV administration of .015 mg of epinephrine with Lidocaine can
increase heart rate 25 to 75 beats and increase systolic blood pressure
20 to 70 mmHg
“Epinephrine reaction” causes tachycardia, sweating, apprehension
and pounding in the chest (palpitations)
Norepinephrine
NOREPINEPHRINE
 Norepinephrine lacks Beta 2 actions (bronchodilation and
vasodilation) and produces intense peripheral vasoconstriction
with possible dramatic elevations in blood pressure
 Norepinephrine’s side effect ratio is 9 times higher than
epinephrine
 Norepinephrine’s 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
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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
1.8 ml Cartridge of 2% Lidocaine 1:100,000 epi
Maximum Epinephrine: 11 Cartridges
Maximum Anesthetic: 300 mg
1.8 ml Cartridge of 2% Lidocaine 1:200,000 epi
Maximum Epinephrine: 22 Cartridges
Maximum Anesthetic: 300 mg
The maximum amount of 2% Lidocaine 1:100,000
epinephrine that can be used is 300 mg which is 8.3
cartridges regardless of the patient’s weight; so the
maximum epinephrine will only be achieved after
you have already surpassed the maximum amount of
anesthetic allowable
8.3 cartridges
American Heart Association says that the
typical concentrations of vasoconstrictors
in local anesthetics are not contraindicated
in patients with cardiovascular disease so
long as aspiration, slow injection and the
smallest effective dose is administered;
ASA III and ASA IV pose the largest risk
How much Epinephrine in CV patients?
Maximum Epinephrine
.04 mg
Two cartridges of 1:100,000 epinephrine
Clinical Applications of Epinephrine
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Management of acute allergic reactions
Management of bronchospasm
Management of cardiac arrest
Vasoconstrictor for hemostasis
Vasoconstrictor to decrease absorption into CVS
Vasoconstrictor to increase depth of anesthesia
Vasoconstrictor to increase duration of anesthesia
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
2 vasoconstrictors are available in North America:
1) Epinephrine
2) Levonordefrin
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