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 3 rd are termed catechols and 4 th positions of the aromatic ring

Catecholamines

If the 3 rd and 4 th 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

*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  2) Indirect Acting  directly on adrenergic receptors 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  -Alpha 2  excitatory; post-synaptic 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 .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 trauma 2) Nick the papilla with a bur; resin or alloy 3) Oral surgery root tip removal; bloody socket 4) Works awesome for short period of time 5) 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

• • • • • • • • • • • • 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

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 1/6 th as potent as epinephrine • Levonordefrin has a maximum recommended dose of 11 cartridges

-Levonordefrin is only 1/6 th 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. 5 th Edition. Mosby. 2004