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Transient
completely reversible
R
------------------- O
Aromatic portion Ester Or Amide
R
Amine portion
In the presence of high conc. Of H ion (low PH), the equilibrium shifts to the left and most of anesthetic sol exists in cationic form
RNH+> RN+H+
As hydrogen ion decreases ( higher pH) the equilibrium shifts to the free base form
Sodium channel
Lipid bilayer
Sodium channel
Lipid bilayer
Diffusion
Keep in Mind:
Nerve Fiber.single nerve cell Endoneurium covers each nerve cell Fasculi..bundles of 500 to 1000 nerve Perinurium.. Cover fasculi Perilemma.. Inner most layer of perinurium Epineurium alveolar connective tissue supporting fasculi and carrying nutrient vessels
2. Concentration.
Duration of action
Short acting L.A (5-40 min.): Without Vasoconstrictors: Lidocaine 2%. Prilocaine 4%. Mepivacaine 3%.
Duration of action
Medium Acting (45- 90 min.) Lidocaine 2% with epinephrine.
Duration of action
Long Acting (> 90 min.) Bupivacaine 0.5% with epinephrine.
the local anaesthetic >>>> absorbed from the site of administration into circulation. The presence of a local anaesthetic drug in the circulatory system means that drug will be transported to every part of the body.
What does body do to the drug ? What the drug do to the body?
Pharmacokinetics
Uptake
Local Action: All local anesthetics posses a degree of vasoactivity, mostly vasodilatation except Cocaine which causes vasoconstriction.
Oral Route: All local anesthetics are poorly absorbed from the GIT except cocaine Most LA undergo hepatic first-pass after administration where 72% of the drug is transformed into inactive metabolites
Topical Route
Application to mucous membranes
Injection
The rate of uptake of local anesthetic after parental administration (subcutaneous, intramuscular or iv) is related to vascularity of the site and vasoactivity of the drug
Distribution
Local anesthetic absorbed and distributed to all tissues in the body. Intravascular injection results in a sequential distribution first to the lung then rapidly distributed to other organs with large blood supplies, especially the brain, heart, liver, kidneys, spleen and then to muscle and fat.
Biotransformation
Esters
Metabolized In plasma by the enzyme pseudocholine esterase Amides Metabolism In the liver by microsomal enzymes
Excretion
Kidneys are excretory organs for ester & amide anesthetics and their metabolites Patients with renal dysfunction may be unable to eliminate local anesthetics
At low therapeutic ,non toxic doses no CNS effects of any clinical significance is manifested
At higher toxic overdose levels the primary clinical manifestations is generalized tonic-clonic convulsions Between these two extremes there are preconvulsive signs and symptoms
Preconvulsive stage
Signs(objectively observable) Slurred speech Shivering Muscle twitches Visual disturbance
Drowsiness
Disorientation Symptoms (Subjectively felt) Numbness of tongue and circumoral region Warm flushed feeling of skin
Convulsive stage
Further elevation of LA blood levels leads to signs and symptoms of Tonic conic convulsive episode further increase will lead to depression
Inhibitory impulses
Faclitatory impulses
Cardiovascular system
Action on myocardium : local anesthetics produce a myocardial depression that is related to drug blood level Decrease cardiac excitability Decrease conduction rate Decrease force of contraction Used for treatment of cardiac dysrhythmias
Cardiovascular system
Direct action on peripheral vasculature:
Respiratory System
Has dual effect on respirations
At non overdose level they have a direct relaxant action on bronchial smooth muscle
As a result of CNS depression respiratory arrest may occur
Vasoconstrictors
vasoconstrictors constrict blood vessels It counteract vasodilating effect of the local anesthetics.
Vasoconstrictors
Advantages:
Increase the concentration of drug at the site: Prolong anesthetic duration. Produces more profound anesthesia. Decrease the blood level of the drug, thus reduce the risk of toxicity. Decrease bleeding at site.
Vasoconstrictors
Systemic effects of vasoconstrictors: Vasoconstrictors are sympathomimetic i.e. they mimic the action of norepinephrine on sympathetic effector organs where they bind to specific receptors called adrenergic receptors. These receptors are divided into alpha () and beta ( ) receptors.
Vasoconstrictors
Alpha () receptors
Alpha 1 (1)
Smooth muscles of the BVs vasoconstriction
Alpha 2 (2)
Inhibitory receptors
Vasoconstrictors
Beta ( ) receptors
Beta 1 ( 1)
In the heart increase rate and force of contraction
Beta 2 ( 2)
In bronchi bronchodilation In coronaries vasodilation.
Vasoconstrictors
Nor-epinephrine excites mainly alpha receptors and to slight extent beta receptors.
with
slight
Vasoconstrictors
Mode of action: In the small amounts commonly used in dentistry,
Vasoconstrictors
Disadvantages:
Vasoconstrictors
Dilution of vasoconstrictors: The dilution of vasoconstrictors is commonly referred to as a ratio (e.g. 1:1000) this ratio can
1:100.000 = 0.01 mg / ml ?
1 ml 1.8 ml
Vasoconstrictors
Epinephrine:
Nature:
Known as adrenaline. Most commonly used due to its strong action. Stability: Unstable, undergo oxidation by heat. Sodium bisulphite preservative used to delay oxidation
Epinephrine (adrenaline):
Systemic effect: Increase blood pressure. Increase heart rate. Increase cardiac output. Increase myocardial oxygen consumption. Vasculature Hemostasis: vasoconstriction followed by vasodilatation
Vasoconstrictors
Norepinephrine (levarterenol): Nature: Known as noradrenaline . Stability:
That will lead to severe vasoconstriction in the peripheral circulation (ischemia in the palate ) Available consentration 1:300.000 Norepinephrine:
Maximum permeable dose:
For healthy patient 0.34 mg/appointment. For cardiac patient 0.14 mg/appointment.
Vasoconstrictors
Levonordefrin:
Nature:
It is synthetic vasoconstrictor. It has direct action on the 15% as potent as epinephrine receptors(75%) & it is
Stability:
Unstable, undergo oxidation and deterioration. Sodium bisulphite used to delay oxidation.
Systemic effect:
Less effective in contrating blood vessels and in raising blood pressure than epinephrine. It is 1/10 as active as epinephrine in increasing blood sugar.
Levonordefrin:
Concentrations in L.A:
1:20,000.
Vasoconstrictors
Phenylephrin:
Nature:
Synthetic. It has direct action on the epinephrine receptors(95%) & it is 5% as potent as
Stability:
Most stable vasoconstrictor used in dentistry.
Concentrations in L.A:
Used in dental practice with 4% procaine in 1:2500 dilution.
Phenylephrin:
Maximum permeable dose:
For healthy patient 4 mg/appointment. Far cardiac patient 1.6 mg/appointment.
Vasoconstrictors
Felypressin:
Nature:
Synthetic analogue of the antidiuretic hormone vasopressin. Act directly on the smooth muscles in the wall of the blood vesseles It is non sympathomimetic amine, so it has no effect on adrenergic nerve transmission safe for hyperthyroid patients.
Systemic effect:
It has oxytoxic action so it is contraindicated in pregnant women.
Concentration in L.A:
Used in dental practice with 3% prilocaine in a 0.03 IU/ml dilution.
Procaine ( Novocain)
Nature ester types L.A. Metabolism in plasma by pseudocholinestrases enzymes. Excretion Via kidney. Onset: 6-10 min Dental concentration 2% or 4% conc. 2% solution gives from 12-15 minutes of anesthesia The addition of 1:100.000 adrenaline prolong the duration to 30-45 minutes
Propoxycaine HCL
Nature ester types L.A. Metabolism in plasma by pseudocholinestrases enzymes. Excretion Via kidney. Onset: rapid 2-3 min Dental concentration 0.4% conc. It is combined with procaine to provide more rapid onset and a more profound anaesthesia
Articaine HCl.
Bupivacaine HCL Prilocaine HCL
Metabolism: liver. Excreation: kidneys. Vasodilating properties: produce slight V.D. Duration of action: without V.C. 20-40 min. Onset of action: rapid 1.5-2 min. Effective dental concentration: 3% without V.C.; 2% with a V.C. Pregnancy classification: C Concentrations of V.C.: 2% with levonordefrin (1:20,000), 2% with epinephrine (1:100,000).
Prilocaine (Citanest)
Nature Amides Local Anesthesia. Metabolism In liver, kidney & lung so it undergo biotransformation more rapidly than other amide. Excretion Via kidney faster than other amide. (most safe) Dental concentration 4% with or without V.C. V.C used with it is 1:200.000 Epinephrines. Onset of action Its onset of action is slightly slower than Lidocaine Maximum dose 6 mg/ kg body weight or 400 mg
Bupivacaine (Marcaine)
Nature Amides Local Anesthesia + long acting L.A. Metabolism In liver. Excretion Via kidney. Dental concentration 0.25% 0.5% conc. With 1:200.000 Epinephrine . Onset of action Rapid onset of action equal to lidocaine. Maximum dose 2 mg/ kg body weight for adult- 90 mg as maximum dose .
20 mg / ml ?
1 ml 1.8 ml
The doses of local anesthetic drugs are presented in terms of milligrams of drug per unit of body weight.
The administration of a maximum dose based on body weight produces a local anesthesia blood level just below the threshold for an overdose (toxic) reaction.
mg/Kg
MRD (mg)
Lidocaine
300 300
Mepivacaine
300 300
Articaine
40
72
Lidocaine
20
36
Mepivicaine
2 3
20 30
36 54
Total dose of Both local anaesthetics should not exceed the lower of the two calculated dose.
1 mg
4 mg
0.2 mg
1.6 mg 0.27 IU,
Felypressin
0.03 IU
Topical anesthesia
Topical Anesthesia
Produce painless needle injection. Used for some procedures as removal of very loose primary teeth or suture removal or before gingival curettage. Reduce patient apprehension.
Topical Anesthesia
Characteristics: Can not penetrate intact skin. Its concentration is higher than injectable one to facilitate its diffusion through mucous membrane. Higher concentration increase its risk of toxicity because the topical anesthesia has no V.C.
Topical Anesthesia
Characteristics: The anesthesia is effective only on 2.3 mm depth of the tissues on which it is applied. Available in the form of spray or gel, the gel form is more preferred because it can be dispensed in a
premeasured doses.
Topical Anesthesia
Types of local anesthesia:
Benzocaine.
Lidocaine HCl.
Lidocaine base.
Tetracaine HCL. Cocaine HCl. EMLA (Eutectic Mixture of Local Anesthesia).