Composition of local ansthesia

Local anesthesia

Lecture 3

Composition of local anesthetic solution

Local anesthetic agent Vasoconstrictor Preservative Reducing agent Fungicidal agent Sodium chloride and distilled water

Other agents: TCAD Tramadol Diphenhydramine meteclopromide neosaxitoxin

Local anesthetic agent

Amide Lidocaine Mepivicaine Prilocaine Articaine Bupivicaine Etidocaine

Ester Cocaine Procaine Propoxycaine

Lidocaine


Most common agent Discovered in 1948 ( first of amide group) Regarded as the standard Minimal allergisity Have topical anesthetic activity Vasodilating activity PKa =7.9


Onset of action = 2-3 min Duration = 60 min (pulpal) and 60-120 min (soft tissue) Maximum recommended dose (MRD)= 4.4mg/kg =300 mg

Metabolism and safety

Lidocaine metabolized in liver and excreted in urine (10% unchanged completely)? Contraindicated in end stage liver disease On CNS large dose cause initial stimulation followed by depression ( anticonvulsant effect) On CVS large dose cause myocardial depression ( used in ventricular tachycardia)

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Maximum dose calculation

Available concentration =2% =2gm in each 100 ml /100 →→→→0.02gm/ml = 20 mg/ml*2 ml/dental cartridge =40 mg /dental cartridge300 /40 = 7.5 dental cartridge (MRD)

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Mepivicaine


Same potency to lidocaine Similar to lidocaine in metabolism and excretion Same onset slight extended duration (weak vasodilatation) PKa =7.6


Less toxic than lidocaine Used for child and geriatric patient when vasoconstrictor contraindicatedMRD =4.4 mg/Kg= 300mg 2% → 7.5 cartridge3% → 5 cartridge

Prilocaine (citanest)

Same potency to lidocaineLess toxicityLess vasoldilating activity PKa =7.9MRD =6mg/kg3% → ?? cartridge4% → ??? cartridge

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Prilocaine (citanest)


Metabolism occur mostly in liver into orthotolidine which can cause methemoglobulinemia in susceptible individual (patient with hemolytic anemia) if used in large dose → poor oxygen carrying capacity resulting in cyanosisClinically patient may have cyanosis in the lip, mucous membrane and skin. Patient may also have respiratory distress in severe casesTreatment by methyline blue 1% injection 1-2 mg/kg IV/5min

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Articaine


Slightly more potent than lidocaineSimilar toxicity, and vasodilating activitySome literature present a cross allergisity with sulfate so it is best to be avoided in patient allergic to sulfonamide MRD =7mg/kg 4% → 7 cartridgeSimilar to prilocaine in producing methemoglbulinemia

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Bupivicaine


Four times more potent than lidocaine and 4 times less toxic Slower onset (5-10 min) and extended duration lasting for 90-180 minMRD =1.3mg/kg 0.5% → 10 cartridge


Dental Indication Prolonged dental procedure Expected post operative pain Contraindication Child and mentally retarded patient

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Etidocaine


Similar to bupivicaine except:More toxic than lidocaineMRD= 8mg /kg available in1.5% → 13 cartridge In general surgery both indicated in prolonged procedure when uses of vasoconstrictor is contraindicated systemically or locally

Ropivicaine

A newer long acting local anethesia as an isomer of bupivicaine with minimum toxicity and more effectiveness

Local anesthetic agent

Amide Lidocaine Mepivicaine Prilocaine Articaine Bupivicaine Etidocaine

Ester Cocaine Procaine Propoxycaine

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Cocaine

Oldest anesthetic agent used since 18th century It is the only agent having a vasoconstrictor activity( sympathomimatic activity) and can be used topically because it is rapidly absorbed through mucous membrane It has liability for dependence which makes its uses very limited

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Procaine


Has 50% potency and toxicity than lidocaine It has prominent vasodilating activity which reduce its duration PKa =9.1 (slow onset) MRD =1000mg


Its hydrolyses occurs in plasma by enzyme pseudocholine esterase High incidence of allergisity

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Propoxycaine



More potent and more toxic than lidocaine Has rapid onset and adequate duration It is available in combination form with procaine to reduce toxicity 0.4% propoxycaine + 2% procaine =24mg/ml MRD =400 mg It is indicated only in patient allergic to amide form of local anesthesia


H W


MD calculation in prilocaine Other agents having local anesthetic properties WriteAbout EMLA, carbonated local anesthesia

Composition of local anesthetic solution

Local anesthetic agent Vasoconstrictor Preservative Reducing agent Fungicidal agent Sodium chloride and distilled water

Vasoconstrictor

Advantages of vasoconstrictor in combination with local anesthesia: Reduce blood flow thus reduce bleeding Reduce local anesthetic absorption and toxicity (reduce systemic effect) Increase duration and depth of anesthesia

Types of vasoconstrictor

Adrenergic agonist agent Vasopressin

Adrenergic agonist agent (sympathomimetic agent) - catecholamine

Mode of action: Direct (binding) Indirect (displacing) Mixed action


Sympathetic receptors:1 vasoconstriction2 Reuptake1 Cardiac stimulation2 Vasodilatation


-
-
+
+
Phenylphrine
+
++
++
+
Levonordephrine
-
-
++
++
Nor - adrenaline
++
++
++
++
Adrenaline
2 1 2 1

Affinity of adrenergic agents on receptors

OH
CH
CH
1
NH
Epinephrine
Levonordefrin
Norepinephrine
CH
H
H
3
H
CH
H
3
1
2
HO
2
HO

Adrenaline

Synthetic or natural abstract from adrenal medulla . It is the most common and potent vasoconstrictor. Concentration: Expressed in ratio gm: ml / 1: 100000 Meaning 1 gm in 100000 ml

Concentration

1:100000 means: =1 gm in 100000 ml =1000 mg in 100000 ml= 0.01 mg /mlIn single dental cartridge (1.8 ml)= 0.018 mg =18 g (microgram)

Adrenaline availability (concentration)

1:1000 (alone) is used for control of bleeding? contraindicated in arterial bleeding- Rebound bleeding 1:50000 for surgery where hemostasis is necessary 1:80000 and 1:100000 commonly used concentration 1:200000 low concentration used for medically compromised patient (vasoconstrictor contraindicated) and where hemostasis is of little importance


15
1:20000
1
levonordephrine
5
1:2500
4
Phenylphrine
25
1:30000
0.34
Nor - adrenaline
100
0.2
Adrenaline
Potency
Available concentration
MRD (mg)

Maximum recommended dose (MRD)

Other adrenergic agonist vasoconstrictor


Nor-adrenaline and phenylphrine have prominent alpha activity comparing to beta activity which may result in severe vasoconstriction (increase blood pressure) and ischemia. It is contraindicated in patients with cardiac problem. It is contraindicated in terminal extremities


MAO
MAO
Receptor
a
Extraneuronal
tissues
Renal
excretion
[ COMT ]
[ COMT]
Adrenergic
nerve terminal
Injected drug
COMT: Catechol-O-methyltransferase MAO: monoamine oxidase

Metabolism of catecholamines

Side effects and overdose


CNS: Fear apprehension palpitationCVS: Cardiac stimulant effects , increase blood pressure and rebound bleeding at prolonged dental procedure. Causes of rebound bleeding:Adrenaline selectivity on receptor:Low concentration  effectHigh concentration  effect

Limitation of adrenergic vasoconstrictor

Precautions/contraindications Uncontrolled Cardiovascular disease Uncontrolled thyrotoxic goiter Drug interactions Tricyclic antidepressants General anesthetics Adrenergic antagonists COMT inhibitors Not MAO inhibitors


Vasoconstrictors (epinephrine, Levonordefrin) with Tricyclic antidepressants (imipramine, desipramine)

Hypertensive and/or cardiac reactions are more likely. Use epinephrine cautiously; avoid Levonordefrin.



Vasoconstrictors (epinephrine, Levonordefrin) with

Vasoconstrictors (epinephrine, Levonordefrin) with

Nonselective beta blockers (Propranolol, Nadolol)

Hypertensive and/or cardiac reactions are more likely. Use cautiously.

Vasoconstrictors (Epinephrine, Levonordefrin) with


COMT inhibitors (Tolcapone, Entacapone) Hypertensive and/or cardiac reactions are more likely. Use cautiously.

Consideration

MRD for cardiovascular disease patient = 0.04 mg of adrenaline = 2 dental cartridge of 2ml 1:100000 concentration adrenaline Controversy still exists on using adrenaline in controlled cardiovascular diseased patient. Explain why?



Uses of small amount available in dental cartridge is better than exposing the patient to failure anesthesia which produce pain and bleeding that can stimulate fear and increase intrinsic adrenaline that may have more dangerous effect than extrinsic adrenaline

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Vasopressin (Felypressin)


Synthetic analogue of posterior pituitary hormone (Octopressin) Act on V1 receptor that is found on venous site of microcirculation It posses mild hemostatic effect and used only when other vasoconstrictor contraindicated Available concentration = 0.03 IU/ml in combination with prilocaine 2% or 3% MRD= 0.27 IU

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Preservative


Maintains sterility of the solution Caprylhydrocuprienotoxin used for this purpose Methylparaben used in the past but nowadays omitted ?

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Reducing agent (in vasoconstrictor containing solution)


Antioxidant (reducing agent) used to prevent oxidation of vasoconstrictor that may deteriorate on exposure to sunlight (brown discoloration) Sodium metabisulfite used for this purpose On exposure to oxygen it will diffuse through the rubber of the cartridge where sodium metabisulfite will be converted to sodium metabisulfate (oxidized) Oxidized instead of vasoconstrictor Why is an old solution more acidic? Painful ? Irritant?


Fungicide Thymol Sodium chloride and distilled water (ringers solution) For isotonicity of injected solution to reduce edema and discomfort on injection