Pharmacology of Vasoconstrictors

1
Pharmacology of Vasoconstrictors
2

• 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

3

• 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

4
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

5
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

6
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

7
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.

8
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

9

• 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

10

• 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

11
(No Transcript)
12

• The dilution of vasoconstrictors is commonly
  referred to as a ratio i.e., 150,000 1100,000
  1200,000 etc,
• A concentration of 11,000 means that there is 1
  gram
• (1000 mg) of solute (drug) contained in 1000 ml
  (1 L) of
• solution, therefore, 11,000 dilution contains
  1000 mg
• in 1000 ml or 1.0 mg/ml of solution (1000 ug/ml)
• The concentration of 11,000 is very concentrated
• (strong) a much more dilute form is used in
  dentistry
• for example, 150,000 gt 1100,000 gt 1200,000
• (1100,000 0.01 mg/1 ml of solution)

13
(No Transcript)
14

• per 1.8 ml cartridge of anesthetic
• 150,000 .036 mg epinephrine
• 1100,000 .018 mg epinephrine
• 1200,000 .009 mg epinephrine
• decreasing potency of epinephrine

15

• 150,000 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

16

• Resting plasma epinephrine levels are doubled
  when one cartridge of 2 Lidocaine 1100,000
  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)

17
Norepinephrine
18

• 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

19
Epinephrine
20
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

21

• 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

22
(No Transcript)
23

• 1.8 ml Cartridge of 2 Lidocaine 1100,000 epi
• Maximum Epinephrine 11 Cartridges
• Maximum Anesthetic 300 mg
• 1.8 ml Cartridge of 2 Lidocaine 1200,000 epi
• Maximum Epinephrine 22 Cartridges
• Maximum Anesthetic 300 mg

24

• The maximum amount of 2 Lidocaine 1100,000
  epinephrine that can be used is 300 mg which is
  8.3 cartridges regardless of the patients
  weight so the maximum epinephrine will only be
  achieved after you have already surpassed the
  maximum amount of anesthetic allowable
• 8.3 cartridges

25

• 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

26
How much Epinephrine in CV patients?

• Maximum Epinephrine
• .04 mg
• Two cartridges of 1100,000 epinephrine

27

• 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)

28
Levonordefrin
29

• 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)

30

• 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
  120,000 used at a higher concentration, i.e.,
  120,000 because it is
• 1/6th as potent as epinephrine
• Levonordefrin has a maximum recommended dose of
  11 cartridges

31

• -Levonordefrin is only 1/6th as strong as
  Epinephrine, therefore, using a ratio of 120,000
  Levonordefrin is like using a ratio of 1120,000
  of Epinephrine
• -you will need more Levonordefrin because it is
  only 15 as effective as Epinephrine

32

• 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

33
(No Transcript)
34
Contraindications to Using Vasoconstrictors

• 1) Blood pressure gt 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)

35
References

• Malamed, Stanley Handbook of Local Anesthesia.
  5th Edition. Mosby. 2004