Local anesthetics,drugs, doses,theories, mechanisms
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Transcript of Local anesthetics,drugs, doses,theories, mechanisms
BY MAYANK CHHABRA
Definition of local anesthesia 1) It is a transient loss of all modalities of sensation such as
pain, touch , temperature and pressure in a localized circumscribed anatomical area by blocking the nerve conduction without loss of consciousness.
2) Local anesthesia is defined as a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings or an inhibition of the conduction process in peripheral nerve. (Handbook of Local Anesthesia , Stanley.F.Malamed 6th ed)
Composition of Local AnestheticSolution
Local Anesthetic agent- 2% Lidocaine
Vasoconstrictor- Epinephrine1:80,000 to1:200,000
Reducing Agent- Sodium Metabisulphite
Preservative- Methyl Paraben
Solvent- Distilled Water
1) It should not be irritating to the tissue to which it is applied.
2) It should not cause any permanent alteration of nerve structure.
3) It’s systemic toxicity should be low.
4) It must be effective regardless of whether it is injected into the tissue or is applied locally to mucous membranes.
5) The time of onset of anesthesia should be as short as possible.
6) The duration of action must be long enough to permit completion of the procedure yet not so long as to require an extended recovery.
Other desirable qualities listed by Bennett :-
7) It should have have potency sufficient to give complete anesthesia without the use of harmful concentrated solutions. 8) It should be relatively free from producing allergic reactions.
9) It should be stable in solution and should readily undergo biotransformation in the body. 10) It should be sterile or capable of being sterilised by heat without deterioration.
A) Based on duration of action: 1) Ultra Short acting anesthetics (less than 30
mins)-
2-Chloroprocaine without a vasoconstrictor 2% Lidocaine without vasoconstrictor
2) Short acting anesthetics(45 to 75 mins)-
2% Lidocaine with 1:1,00,000 epinephrine 4% Prilocaine when used for nerve block
3) Medium acting anesthetics (90-150 mins)-
a) 4% Prilocaine with 1:2,00,000 epinephrine b) 2% Lidocaine and 2% Mepivacaine with vasoconstrictor
4) Long acting anesthetics (180 mins or longer)-
a) 0.5% Bupivacaine with 1:2,00,000 epinephrine b) 0.5% or 1.5% etidocaine with 1:2,00,000 epinephrine
B)Surface Anesthetics:
1)Soluble agents- Eg Cocaine,Lidocaine, Tetracaine
2) Insoluble agents- Eg Benzocaine,Oxethazine
MECHANISM OF ACTION OF LOCAL ANESTHESIA
1. Displacement of calcium ions from the sodium channel receptor site, which permits……
2. Binding of the local anesthetic molecule to this receptor site , which thus produces….
3. Blockade of the sodium channel, and a …
4. Decrease in sodium conductance, which leads to….
5. Depression of rate of electrical depolarization…
6. And a failure to achieve threshold potential level….along with
7. A lack of development of propagated action potentials… which brings about..
8. CONDUCTION BLOCKADE
Theories of mechanism of action of local Anesthesia1) Acetylcholine Theory
2) Calcium Displacement Theory
3) Surface Charge Theory
4) Membrane Expansion Theory
5) Specific Receptor Theory
ACETYLCHOLINE THEORY, CALCIUM DISPLACEMENT THEORY andSPECIFIC CHARGE THEORY
Are discredited .
Membrane Expansion Theory
Local Anesthetics are highly lipid soluble & easily penetrate lipid portion of cell membrane
Thus causing expansion of nerve membrane & resulting in the decrease of the diameter of the sodium channels
Thereby inhibiting the influx of sodium & nerve impulse generation.
Specific Receptor Theory
Local Anesthetics act by binding to specific receptor binding site present on the sodium channels
Specific receptor site are present on either the external or internal surface of the sodium channels
Local Anesthetics are classified according to biological site & mode of action
1)Agents acting at receptor site on external surface of nerve membrane- biotoxins (eg. tetrodotoxin)
2)Agents acting at receptor site on internal surface of nerve membrane - quaternary ammonium analogues of lidocaine
3)Agents acting by a receptor-independent physico-chemical mechanism -benzocaine,
4)Agents acting by combination of receptor & receptor - independent mechanism -articaine lidocaine, mepivacaine, prilocaine
Biologically active substances are frequently administered as very dilute solutions which can
be expressed as parts of active drug per 100 parts of solution (grams percent)
Ex.: 2% solution =
_2 grams = _2000 mg = __20 mg 100 cc’s 100 cc’s 1 cc
Injectable Local Anesthetic Agents
1)Amide local anesthetics
Maximum Recommended Dosage
A)To calculate the maximum amount of Lidocaine 2% with 1:100,000 epinephrine and the number of carpules that can be safely administered to a 30 pound patient
B)To calculate the maximum amount of Mepivacaine 3% plain and the number of carpules that can be administered to a 30 pound patient the clinician would perform the following calculations.
DESCRIPTION OF INDIVIDUAL ANESTHETIC AGENTSA) ESTER-TYPE LOCAL ANESTHETICS1) PROCAINE- Present as Procaine HCl. -Is an ester type local anesthetic , is ester of PABA. -Prepared by Alfred Einhorn in 1904. - Potency= 1. -Toxicity= 1. - Metabolized rapidly by hydrolysis, in plasma by pseudocholinesterase. - Onset of action= 6 to 10 minutes. - Half life= 6 minutes. - Effective concentration in dental use= 2% , 4%.
2)PROPOXYCAINE-Present as Propoxycaine HCl. - Is an ester type local anesthetic,is ester of PABA. - Prepared by Clinton and Laskowski in 1952. - Potency= 7 compared to Procaine= 1. - Toxicity= 7 compared to Procaine= 1. - Metabolized by hydrolysis in both plasma and liver. - Onset of action= 2 to 3 minutes. - Effective concentration in dental use= 0.4%
B) AMIDE-TYPE LOCAL ANESTHETICS1)Lidocaine Potency is 2 & toxicity is 2 pKa is 7.9 ph 6.5 pH with vasoconstrictor 5 to 5.5 Vasodilating Concentration available- 2% Dental Concentration 5% Topical Agent 10% Spray Maximum Recommended Dose with vasoconstrictor 7 mg/kg and without vasoconstrictor 4.4 mg/kg
Onset of action 2-3 minutesHalf-life 1.6 hourMetabolized in liver by microsomal fixed function oxidases
2)MepivacaineAmide groupPotency-2 toxicity- 1.5 to 2pKa 7.6 pH 4.5pH with vasoconstrictor 3 to 3.5VasodilationConcentration- 3% without vasoconstrictor 2% with vasoconstrictor
Onset of action 1.5 to 2 minutesHalflife-1.9 hoursMaximum Recommended Dose- 6.6mg/kg
3) PRILOCAINE-Present as Prilocaine HCl. - Is an amide type local anesthetic. - Prepared by Lofgren and Tegner in 1953. - Potency= 2 compared to Procaine= 1. - Toxicity= 2 compared to Procaine= 1. - Metabolized in liver by amidases. - Onset of action= 2 to 4 minutes. - Half life= 90 minutes. - Effective concentration in dental use= 4%.
4) ARTICAINE-Present as Articaine HCl. -Is an amide type local anesthetic. -Prepared by H.Rusching et al in 1969. -Potency= 3 compared to Procaine= 1. -Toxicity= 2 compared to Procaine= 1. -Metabolized both in plasma and liver by plasma esterase and microsomal enzymes. -Onset of action= 2 to 3 minutes. -Half life= 30 minutes. -Effective concentration in dental use= 4%.
5)BupivacaineAmide groupPotency 4 time lidocaine toxicity 4 times less than lidocainepKa-8.1pH 4.5 to 6pH of vasoconstrictor 3 to 4.5Vasodilation more than lidocaine but less than procaineConcentration 0.5%Maximum Recommended Dose 1.3 mg\kgOnset of action 6 to 10 minutesHalflife 2.7 hoursMetaboilsm in liver by amidases
Eutectic Mixture of Local Anesthetics EMLA cream is emulsion with oil phase composed
of lidocaine 2.5% & prilocaine 2.5%(1:1) It was designed as a topical anesthetic able to
provide surface anesthesia of intact skin Used primarily before painful procedure EMLA has become popular during circumcision , leg
ulcer debridement & gynecological procedure It is applied 1hour before procedure EMLA is contraindicated for use in patient with
congenital or idiopathic methemoglobinemia, infants under 1 2 months receiving methemoglobin-inducing agents or patients with sensitivity with amide group
VasoconstrictorVasoconstrictors are important addition to local anesthetic solution due to following reasons
To decrease the perfusion To decrease absorption of local anesthetic
Minimise the risk of toxicity
Increase the duration of action
Decrease the bleeding
Epinephrine It is most potent & widely used vasoconstrictor in
dentistry It is available in following dilution 1:50,000,1:80,000,1:100,000,1:200,000, 1:300,000 Systemic Actions On myocardium increases force of contraction &
rate of contraction Increased heart rate & cardiac output On coronary arteries causes dilation thus
increases coronary blood flow Systolic blood pressure increases & diastolic
pressure decreases in small doses
In large doses diastolic pressure is increased
On blood vessels supplying skin , mucous membranes & kidneys produces vasoconstriction
On blood vessels supplying smooth muscles cause vasodilation on small doses & vasoconstriction on large doses
It is potent bronchodilator
Contraindications for VasoconstrictorAbsolute Contraindication :-Uncontrolled Hypertension
Severe Cardiovascular diseases such as Acute Myocardial Infarction within 6 months, Angina , Refractory Cardiac Dysrhythmias
Hyperthyroid state
Relative ContraindicationsPatients on MAO inhibitors
Patients on Tricyclic Anti-depressents
Arteriosclerosis
Diabetes Mellitus
Stanley Malamed, Handbook of Local Anesthesia, Sixth Edition
www.dentalcare.com