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 dilate2) Increase absorption of the local anesthetic into the cardiovascular system (redistribution)3) Higher plasma levels increased risk of toxicity4) Decreased depth and duration of anesthesia diffusion from site5) 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 StructureClassification 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

CatecholaminesIf the 3rd and 4th positions contain an amine group (NH2) attached tothe aliphatic side chain, they are then called catecholamines

EpinephrineNorepinephrine natural catecholamines of sympathetic NSDopamine

Isoproterenol and synthetic catecholamineLevonordefrin

Chemical Structure Catecholamines Noncatecholamines*Epinephrine Amphetamine*Norepinephrine Methamphetamine*Levonordefrin Ephedrine Isoproterenol Mephentermine Dopamine Hydroxyamphetamine

Metaraminol Methoxamine Phenylephrine

Felypressin synthetic analogue of vasopressin (ADH); not in U.S.

Modes of Action3 Classes of Sympathomimetic Amines:

1)*Direct Acting directly on adrenergic receptors2) Indirect Acting use norepinephrine release3) 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 mgin 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 .036 mg epinephrine 1:100,000 .018 mg epinephrine 1:200,000 .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

1) Bleeding areas that require resin from any trauma2) Nick the papilla with a bur; resin or alloy3) Oral surgery root tip removal; bloody socket4) Works awesome for short period of time5) 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, apprehensionand pounding in the chest (palpitations)

Norepinephrine

NOREPINEPHRINENorepinephrine 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 • 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 epiMaximum Epinephrine: 11 CartridgesMaximum Anesthetic: 300 mg

1.8 ml Cartridge of 2% Lidocaine 1:200,000 epiMaximum Epinephrine: 22 CartridgesMaximum 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 vasoconstrictorsin local anesthetics are not contraindicatedin patients with cardiovascular disease so long as aspiration, slow injection and thesmallest effective dose is administered;

ASA III and ASA IV pose the largest risk

How much Epinephrine in CV patients?

Maximum Epinephrine

.04 mgTwo cartridges of 1:100,000 epinephrine

Clinical Applications of Epinephrine1) Management of acute allergic reactions2) Management of bronchospasm3) Management of cardiac arrest4) Vasoconstrictor for hemostasis5) Vasoconstrictor to decrease absorption into CVS6) Vasoconstrictor to increase depth of anesthesia7) Vasoconstrictor to increase duration of anesthesia8) 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 hemostasis3) 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)

ReferencesMalamed, Stanley: Handbook of Local Anesthesia. 5th Edition. Mosby. 2004