VASOCONSTRICTORS
MODERATOR – DR RAMYA REDDY
PRESENTER – ASHISH VN
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CONTENTS
• Introduction
• Chemical Structure
• Classification
• Mechanism Of Action
• Maximum recommended dose of adrenaline
• Dilution of vasoconstrictors
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CONTENTS
• Pharmocology of Specific agents
• Selection of vasoconstrictors
• References
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INTRODUCTION
• Drugs that constrict blood vessels and thereby control tissue perfusion
• Added to L.A to oppose the inherent vasodilatory action
• Chemically identical to sympathetic nervous system mediators eg. Epinephrine,
norepinephrine
• They are classified as adrenergic drugs or sympathomimetic drugs.
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INTRODUCTION
Actions –
• Decrease blood flow to the site of administration.
• Slows the rate of absorption of LA into the CVS
• Reduce blood levels of LA- reduce toxicity
• Increases the duration & depth of action
• Decrease bleeding at site of administration
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CHEMICAL STRUCTURE
• Classification of sympathomimetic drugs by chemical structure is related to the presence
or absence of a catechol nucleus
• Sympathomemitic drugs that have hydroxyl(oH) substitutes at the 3rd and 4th positions of
aromatic ring are termed as Catechols
• Catechol – orthodihydroxybenzene
• If they contain an amine group(NH2) attached to the aliphatic side chain, they are called
Catecholamines 6
CHEMICAL STRUCTURE
CATECHOLAMINES –
Isoproterenol
Levnordefrin
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CLASSIFICATION
CATECHOLAMINES NONCATECHOLAMINES
EPINEPHRINE AMPHETAMINE
NOREPINEPHRINE METHAMPHETAMINE
LEVONORDEFRIN EPHEDRINE
ISOPROTERENOL MEPHENTERINE
DOPAMINE METARAMINOL
PHENYLEPHRINE
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MECHANISM OF ACTION
1)Adrenergic Receptors – These receptors are found in most tissues of the body. –
Ahlquist (1948)
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MECHANISM OF ACTION
Alpha receptors –
• Contraction of smooth muscle in blood vessels – vasoconstriction
- α-1 - excitatory post-synaptic
- α-2 - inhibitory post-synaptic
Beta receptors
• Smooth muscle relaxation -- vasodilation/bronchodilation
• Cardiac stimulation -- ionotropic, chronotropic, dromotropic
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MECHANISM OF ACTION
1) β1 -found in heart and small intestines
-produces cardiac stimulation and lipolysis
2) β2 -found in bronchi, vascular beds and uterus
-produces bronchodilation , vasodilation , relaxation of uterus
2)Release of Catecholamines
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DILUTION
• The dilution of vasoconstrictors is commonly referred to as a Ratio
• 1:1,000 1 g of drug in 1000 ml (1 L) of solution
1000 mg in 1000 ml
1.0 mg/ml of solution (1000 ug/ml)
• Vasoconstrictors used in Dentistry are more dilute
1:100,000 ---- 1ml = 0.01mg
1:200,000 ---- 1ml= 0.005mg
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PHARMOCOLOGY OF SPECIFIC
AGENTS
1) EPINEPHRINE –
Proprietary name: Adrenaline
Source : Secreted by adrenal medulla
MOA: Non selective adrenergic agonist,stimulating α1, α2, beta1,beta2 adrenergic receptors
Chemical Structure:
• Acid salt & highly soluble in water.
• Deterioration by heat and the presence of heavy metal ions.
• Sodium bisulfite added to epinephrine 13
PHARMOCOLOGY OF
SPECIFIC AGENTS
• Shelf life of a cartridge
• containing a vasoconstrictor -- 18 months
• without a vasoconstrictor-- 36 months
Systemic Actions :
• Myocardium ---- stimulates beta 1 receptors
inotropic, chronotropic
• Coronary arteries--- Dilation = CA blood flow 14
PHARMOCOLOGY OF
SPECIFIC AGENTS
• Blood pressure : Small doses --- Systolic BP Diastolic BP
Large doses --- Diastolic BP
• Vasculature --- vasoconstriction
• Primary action on arterioles & precapillary sphincters
• Small dose --- beta 2 ---- vasodilation
• Large dose --- alpha --- vasoconstriction
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PHARMOCOLOGY OF SPECIFIC
AGENTS
• Respiratory system--- beta 2 bronchodilator
Maximum dose :
Healthy patient --- 0.2mg
Cvs patient --- 0.04mg
Side effects :
-Fear or anxiety -Headcache - Respiratory difficulty
-restlessness -Dizziness - Palpitation
-Tension - Pallor
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PHARMOCOLOGY OF
SPECIFIC AGENTS
Clinical Applications:
• Management of Acute allergic reactions
• Management of refractory Bronchospasm
• Management of Cardiac Arrest
• Vasoconstrictor (hemostasis)
• To increase duration in LA,depth and decrease absorption in Cvs
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PHARMOCOLOGY OF SPECIFIC
AGENTS
2)Norepinephrine –
• Proprietary name: Levophed, Noradrenaline, Levarterenol
• Chemical Structure: Relatively stable in acidic solutions, deteriorating on exposure to
light and air.
• Acetone Sodium Bisulfite is added to retard deterioration
• shelf life of cartridge --- 18 months.
• It exists in both levorotatory and dextrorotatary forms.
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• Synthesized and stored in postganglionic adrenergic nerve endings
PHARMOCOLOGY OF
SPECIFIC AGENTS
• Predominant action on alpha receptors
Systemic Actions:
• Myocardium --- beta 1 stimulation ionotropic
• Coronary arteries --- vasodilation
• Heart rate --- reflex carotid & aortic baroreceptors , vagus nerve
• Blood pressure --- systolic & diastolic BP
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PHARMOCOLOGY OF SPECIFIC
AGENTS
• Vasculature --- vasoconstriction
• Respiratory system --- alpha induced constriction of lung artery which reduces airway
resistance. No broncho dilation
• CNS --- overdose--- stimulation
• Metabolism --- metabolic rate, blood sugar level
Tissue oxygen consumption in injection site
Side effects : tissue necrosis & sloughing – hard palate– alpha stimulation
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PHARMOCOLOGY OF
SPECIFIC AGENTS
Clinical Applications: Maximum Dose: 0.34mg in healthy
• Vasoconstrictor in LA 0.14 in CVS disease Pt
• Management of hypotension
3)Levonordefrin –
• Proprietary name: Neo-Cobefrin
• Chemical Structure: freely soluble in dilute acidic solutions.
• Sodium bisulfite is used as the preservative.
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PHARMOCOLOGY OF
SPECIFIC AGENTS
Source: - synthetic vasoconstrictor & prepared by resolution of nordefrin into its optically
active isomers
Mode of action : 75% -- alpha stimulation, 25% -- beta activity
Systemic Actions: Same as Epinephrine but to a lesser extent
Side effects: Same as Epinephrine but to a lesser extent
Maximum Dose: 1mg in Healthy patients
0.4mg in CVS patients
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PHARMOCOLOGY OF
SPECIFIC AGENTS
4)Felypressin –
Proprietary name: Octapressin
Source: synthetic analogue of antidiuretic hormone vasopressin
Mode of Action: direct stimulant of vascular smooth muscle.
venous > arteriolar microcirculation
Systemic Actions: nondysrhythmogenic
• Vasculature--- vasoconstriction
• CNS ---no effect on adrenergic nerve transmission 23
PHARMOCOLOGY OF
SPECIFIC AGENTS
• uterus – antidiuretic & oxytocic
Side effects: minimal and safe
Clinical Applications:
• Vasoconstriction in LA,
• In Prilocaine to decrease absorption and increase duration of action
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PHARMOCOLOGY OF
SPECIFIC AGENTS
5)Phenylephrine Hydrochloride –
Proprietary name: Neo-Synephrine
Chemical Structure: Soluble in water, most stable and weakest.
Source: Synthetic sympathomimetic amine.
Mode of action: -Direct α receptor stimulation ---vasoconstriction
Systemic actions :
• Blood Pressure – Increase SBP and DBP due to α action
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PHARMOCOLOGY OF
SPECIFIC AGENTS
Heart rate – Bradycardia Maximum Dose: 4mg in healthy patients
1.6mg in CVS patients
• CVS – Decreased cardiac output
• Dysrhythymias rare
Side Effects:
• Headache , Tachyphylaxis with long term use
Clinical Applications:
• Nasal decongestant , Mydriasis , Vasoconstrictor , Management of Hypotension 26
SELECTION OF
VASOCONSTRICTOR
a)Length of the dental procedure
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SELECTION OF
VASOCONSTRICTOR
b)Need for hemostasis
• Epinephrine – alpha & rebound beta action
• Norepinephrine – potent alpha stimulator, tissue necrosis
• Phenylephrine – long acting alpha stimulation
• Felypressin -- venous > arterial
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SELECTION OF
VASOCONSTRICTOR
C)Medical status of the patient
•CVS disease – ASA 3,4 (not recommended for dental care)
Felypressin is recommended as safe except in pregnant patients due to oxytocic
actions
•Hyperthyroid state(epinephrine is relatively contrainciated), uncontrolled diabetes
•MOA inhibitors, TCA(norepinephrine absolutely contraindicated) , phenothiazines
•Sulfite sensitivity
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REFERENCES
• Handbook of Local anaesthesia – Stanley F Malamed
• Monheims – Local anaesthesia and pain control in dental practice
• Essentails of Pharmacology – K.D. Tripathi
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