CHAPTER 3  Vasoconstrictor actions so resembles the
PHARMACOLOGY IN VASOCONSTRICTOR
 Most LA are vasodilators
 Vaso – blood vessels
 Dilate – opens up
The degree of vasodilation varies:
 Procaine – the most potent vasodilatory
properties
 Prilocaine & Mepivacaine – the least
potent vasodilatory properties
The degree of dilation depends on:
 The particular anesthetic
 The injection site (is it high vascular?)
 Individual patient response
Dilation of the blood vessels cause an increase in
blood flow to the site of injection (perfusion –
huge increase in blood flow into the site) which in
turn causes:
 An increase rate of anesthetic absorption
into the bloodstream increasing toxicity
 A decrease in the duration of the
anesthetics action
 Increase bleeding in the area due to the
increase flow of blood into the area
 Higher blood/plasma levels
These advantage can be overcome to a certain
extent by adding vasoconstrictors
 Vasoconstrictors are called vasopressors
 Helpful in dentistry where long duration
& more profound anesthesia are required
 Vasoconstrictors are drugs that constrict
blood vessels and thereby control tissue
perfusion
 They added to LA’s to oppose the natural
vasodilatory action of the LA’s
 Vasoconstrictors used with injected LA
are chemically identical or similar to the
sympathetic nervous system mediators
Epinephrine and Norepinephrine
 The 2 vasoconstrictors routinely are
found in the dental local anesthetic in
North America:
Epinephrine (2% Lidocaine w/ 1:50,000 &
1:20,000)
Levonordefrin ( 2% Mepivacaine w/ Levo
1:20,000)
response of adrenergic nerves to
stimulation that they are classified as
sympathomimetic, or adrenergic drugs.
Catecholamines
(OH & NH2) Hydroxyl and Amine group
 Sympathetic “fight or flight” hormones
released by adrenal glands in response to
stress
 Naturally occurring catecholamines of
sympathetic nervous system:
 Epinephrine (Adrenalin) – stress
hormone and neurotransmitter
 Norepinephrine – stress
hormone & neurotransmitter
 Dopamine – neurotransmitter,
precursor to Epi and Norepi “feel
good and focus”
 Sympathomimetic drugs are Direct-Acting
on adrenergic receptors Alpha & Beta
Adrenergic Receptors
 Epinephrine, Norepinephrine &
Levonordephrine activate adrenergic
receptors
 These receptors are found in most body
tissues and divided into 2 types of
adrenergic receptors:
 Alpha – excitatory & inhibitory
actions (constriction of blood
vessels – heart)
 Beta – inhibitory and excitatory
actions (dilation of blood vessels
and lungs and heart stimulation
Epinephrine acts directly on both alpha & beta
 Epinephrine activates alpha receptors –
vasoconstriction
 Activates beta receptors – vasodilation
 “epinephrine reaction” – apprehension.
Tachycardia, sweating, and pounding in
the chest. Epi: Direct effect on CNS
stimulation
Alpha – vasoconstriction of blood vessels smooth
muscles
 a1 - receptors are excitatory
(constriction) heart
 a2 - receptors are inhibitory
Beta – actions predominate
 B1 - heart muscles constriction
(stimulation)
 B2 - smooth muscle relaxation
(vasodilation & bronchodilation) lungs;
dilation of coronary arteries
“You have 1 heart and 2 lungs”
Beta 1 receptors – primarily on the heart
Beta 2 receptors – primarily on the lungs
Vasoconstrictor Drugs:
Benefits versus Risks
 Endogenous release of epinephrine –
release of epinephrine from within
Meaning that a stressed or unhappy patient has a
greater release of epinephrine than those a
normal patient who receives an injection of LA
plus epinephrine as a vasoconstrictor.
 In such a case of stress, the patient’s
blood level of epinephrine is already
higher than normal, then we added a
local anesthetic with epi making the
blood level even higher.
However, at a 1:100,000 epi amount, the blood
pressure and heart rate are minimally affected
 Cardiac dose (2 catridges of epi with
1:100,00)
 Elevation of epinephrine plasma levels is
dose dependent and persists from several
minutes to a half hour so we don’t leave
patient alone after giving a local
anesthetic
 New evidence supports that epinephrine
levels are equal to moderate to heavy
exercise after an oral injection.
Those who should NOT receive an anesthetic with
vasoconstrictor include:
 Patients with recent myocardial
infarction, coronary bypass surgery, or
cerebrovascular accident within the past
6 months
 Patients with uncontrolled hypertension,
angina, arrhythmias, diabetes, and
hyperthyroidism
 Possibly can have a cardiac dose
Dilution of Vasoconstrictors
 stated as Ratio i.e, 1:1000
 1 gram = 1000 mg
 MRD = maximum recommended dose
uses mg’s
 1:1000 means 1 gram (1000 mg) of solute
(drug) is contained in 1000 ml
 Therefore, a 1:1000 means
1000 mg = 1.0mg/ml (0.3 mg of 1:1000
1000 ml in epi pen)
ml added to 9 ml of sterile H2O
 (this would be too highly concentrated for
LA so they would need to diluted further.
 1:100,000, means 1 gram (1000 mg) of
solute (drug) is contained in 100,000 ml
 Therefore a 1:100,000 meas
1000 mg = 1 = .01 mg/ml
100,000 ml 100
 1 ml of a 10,000 solution is added to 9 ml
of solvent
 2% Lidocaine with epi/ 1:50,000 – strong
 2% Lidocaine with epi/ 1:100,000
Vasoconstrictor used in LA sol.
 EPINEPHRINE – adrenalin
Concentrations
 1:50,000
 1:100,000
 1:200,000
 Levonordefrin – Neo-Cobefrin
Concentrations
 1:20,000
Epinephrine aka: Adrenalin
 The most useful & best example of a
drug mimicking the activities of the
sympathetic discharge
 Actions of other drug are compared to
Epinephrine – used as the “benchmark”
 Is an acid salt & highly soluble in water –
acid/base
 Slightly acidic solutions are relatively
stable & protected from air
 Sodium Bisulfite is added to epi to delay
deterioration (oxidation) – longer shelf
life
 LA solution w/ no vasoconstrictor = 36
months
  LA solution w/ vasoconstrictor = 18
months
Epinephrine Actions on Specific System
 Epinephrine acts directly on both a & B
receptors
 B effects predominate – vasodilation of
heart (coronary arteries) &
bronchodilation (lungs)
 Cardiac: both alpha and beta (1&2)
 Stimulate beta 1 receptors =
increase heart rate. Stroke
volume, and cardiac output and
also beta 2 effects that dilate
blood vessels and lungs
Blood pressure
 Small doses = increase systolic & decrease
diastolic pressure
 High doses = increase diastolic pressure
Cardiovascular system: Beta 1 effects –
stimulation
 Increase cardiac output, heart rate, stroke
volume, contraction , & increase
systolic/diastolic w/ 1 to 2 cartridges
 Overall decrease in cardiac efficiency
 Metabolic: inhibits insulin secretion (the
diabetic)
Respiratory System
 Beta 2 effects
 Bronchial dilator
 Tx acute asthmatic attacks and
anaphylactic reactions CNS
 Normal dose: does NOT stimulate CNS
 Overdose: CNS stimulation – anxiety,
nausea, restlessness, weakness, tremor,
headache, hyperventilation
 Hemostasis: high doses stimulate alpha
receptors resulting in vasoconstriction
Max Doses of Epinephrine
 1cc = 1ml
 1 cartridge = 1.8 ml
Healthy patient 0.2 mg (1.8ml X .01 mg/ml = .018
mg)
.018 X 11 cartridges = 0.198 or 0.2 mg rounded
Med. compromised patient 0.04 mg (1.8 X .01
mg/ml = .018
.018 X 2 cartridges = .036 or .04 mg rounded
Above calculation are for an epi 1:100,000
dosage
 use lowest possible dose
 proper aspiration
 inject slowly
 Proper technique!!
Hemostatsis: decreasing the bleeding at the site
of injection
 1:50,000 epi is more effective than
1:100,000
 1:100,000 more effective than no
vasoconstrictor and sufficient enough SRP
 1:100,000 for pts who are sensitive to
catecholamines
Levonordefrin – Neo-Cobefrin
 Synthetic vasoconstrictor
 Man made
 Approx. one sixth (15%) as potent as
epinephrine
 Manufactured in higher concentrations
 Vailable ONLY with 2% Mepivacaine in
1:20,000 mg/ml to achieve same effect
as Epi 1:100,000
 Contains sodium bisulfite
 Provides significantly less hemostasis
than Epi
 Can be used in dentistry as alternative to
epi if epi cant be used
Norepinephrine – Levartenerol
 NOT recommended for used in dentistry
& not sold in USA. Authors should
eliminated all together
 Side effect are nine times potent than
those of Epi
 Pain control is only ¼ (25%) potent as Epi
 Can cause necrosis is tissue w/ excessive
use (hardpalate)
Phenylephrine – (Neo-Synephrine)
 No loner used in dentistry; Tachyphylaxis
noted
 Still in use nose spray etc
Felypressin
 Not available
Hemostasis
  Concentrated epi, 1:50,000 provides
greatest hemostasis; used for surgery
 Studies shows effective hemostasis with
1:100,000 for SRP procedure
 No difference in pain control between
1:50,000 and 1:100,000 dilution so use
1:100,000 which is less concentrated
 Epi is rapidly diluted inactivated in blood
stream
 Diluted Epi, 1:200,000 is safer for
cardiovascularly compromised patients
Selection of a Vasoconstrictor
Factors to be considered
1. Length of the procedure
2. Need for hemostasis & after the
procedure
 Need for postop pain control
 Medical status of the patient
Length of the procedure
 The addition of any vasoactive drug to LA
prolongs the duration (&depth) of pulpal
and soft tissue anesthesia of most
anesthetic
 Ex: 2% Lidocaine HCL (plain) provides
pulpal and hard tissue approx. 5-10 min.
the addition of Epi increases to approx. 60
min. (6 times longer)
 The addition of vasoconstrictor to
Prilocaine does not significantly increase
the duration
 The typical pt is scheduled for a 1 hour
apt. duration of actual tx is 47 – 48 min
Requirements for Hemostasis
 Epi prevents or minimizes blood loss
during surgical procedures
 Epi possesses both a and b actions
 Epi produces a ‘rebound’ vasodilatory
effect as the tissue level of epi declines;
possible post op bleeding which may
interfere w/ wound healing
 Used in 1:50,000 concentration, Epi
produces vasoconstriction through it’s a
effect
 Once the a constriction effect has ceased,
epi produces a definite rebound b effect
 Lesser effects w/ 1:100,000 concentration
 Vasoconstriction must be deposited
locally into the surgical site to provide
hemostasis
 Vasoconstrictors acts directly on a
receptors in the vascular smooth muscle
 Only small volume of LA solutions with
vasoconstrictors are required to achieve
hemostasis
Medical Status of the Patient
 Few contraindications are known to
vasoconstrictor concentrations that are
used in today’s dentistry
 The benefits and risks of including a
vasopressor in the LA must be weighed
against using a plain LA
 Establishing the degree of severity of
condition is the key
Concern
 Minimal dosage: patients with non-
cardiovascular disease (ASA 2 or 3);
controlled hyperthyroid dysfunction (no
clinical symptoms) controlled diabetes,
sulfite surgery
 Minimal dosage: patients receiving MAO
inhibitors, tricyclic antidepressant,
phenothiazines (antipsychotic) shows no
great risk with only minimal dosage
 Controlled ASA 2or 3: vasoconstrictors –
just relative contraindication if
administered minimally (2 cartridges) and
slowly even with mild to moderate
cardiovascular disease
 >200/115 blood pressure should NOT
receive elected dental care until condition
is treated
 ASA 3 or 4 with poorly controlled severe
cardio disease is too great od risk for
elective dental care
 Myocardial infarction within last 6
months
 Daily or unstable angina episodes
 Refractory cardiac dysrhythmias
 Poorly controlled and clinically evident
hyperthyroidism (bulging eyes, tremors,
high temp, etc
 Use 1:100,000 sensitive to
catecholamines
Medical status of the patient
 Vasoconstrictors contain Sodium Bisulfite
 Sodium bisulfite is an acidic antioxidant to
prolong shelf life of the vasoconstrictor to
18 months
 Can produce a slightly slower onset
 Sodium bisulfite is the most frequently
used antioxidant used in LA.
 Can produce an allergic reaction
 Sodium bisulfite leaves LA slightly more
acidic (the pH drops) than w/out a
vasoconstrictor
 2% Lidocaine HCL is already slightly acidic.
Sodium bisulfite in the vaso causes the pH
to drop even further
 Sodium bisulfite contains more RNH+
than RN molecules so diffusion into
axoplasm is slower resulting in slightly
slower onset

In dentistry today, adequate pain control of

sufficient clinical duration and depth is difficult to
achieve without inclusion of vasoconstrictors in
the LA solution
Inclusion of a vasoconstrictor should be
considered routine unless specifically
contraindicated by a pt medical status (ASA 4 or
above) or by the short treatment duration

Hyper-responders
 (tremor of arms and legs, drowsiness
etc). Overly responders with duration of
anesthesia longer than normal. 70 – 80
min. adverse reaction with less than
normal doses

Hypo-responders
 Under responders with duration of
anesthesia shorter than normal.
Lidocaine with a vasoconstrictor only
lasting 45, 30 or 15 minutes or even less.
Need much higher doses of LA to show
adverse reactions

Hypersensitivity
 Refers to an allergic process that involves
antigen-antibody responses
 True allergic response are NOT dose
related