Local anesthesia

1. LOCAL
ANESTHESIA
Dr. Amitha
Dept of Oral
pathology

2. CONTENTS
 DEFINITION
 CLASSIFICATION
 MECHANISM OF ACTION
 COMPOSITION
 LOCAL ANESTHETIC AGENTS
 VASOCONSTRICTORS

3. DEFINITION:
 IT IS THE 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 NERVES

4. CLASSIFICATION
 ESTERS
 ESTERS OF BENZOIC ACID:
 BUTACAINE
 COCAINE
 BENZOCAINE (ETHYL AMINO
BENZOATE)
 TETRACAINE
 ESTERS OF PARA-
AMINOBENZOIC ACID
 CHLORPROCAINE
 PROCAINE
 PROPOXYCAINE
 AMIDES
 ATRICAINE
 BUPIVACAINE
 DIBUCAINE
 ETIDOCAINE
 LIDOCAINE
 MEPIVACAINE
 PRILOCAINE
 ROPIVACAINE
 QUINOLINE
 CENTIBUCRIDINE

5. Esters vs Amides
 The ester linkage is more easily broken so the ester drugs are less
stable in solution and cannot be stored for as long as amides.
 Amide anaesthetics are also heat-stable.
 The metabolism of most esters results in the production of para-
aminobenzoate (PABA) which is associated with allergic reaction.
 Amides, in contrast, very rarely cause allergic phenomena. For these
reasons amides are now more commonly used than esters.

6. BASED ON MODE OF APPLICATION
 INJECTABLE
 LOW POTENCY, SHORT
DURATION
 PROCAINE
 INTERMEDIATE POTENCY
AND DURATION
 LIGNOCAINE (LIDOCAINE)
 HIGH POTENCY, LONG
DURATION
 TETRACAINE, BUPIVACAINE,
ROPIVACAINE, DIBUCAINE
 SURFACE/TOPICAL
 SOLUBLE
 COCAINE, LIGNOCAINE,
TETRACAINE, BENOXINATE
 INSOLUBLE
 BENZOCAINE,
BUTYLAMINOBENZOATE
(BUTAMBEN)

7. BASED ON DURATION
 ULTRA SHORT ACTING (<30 MINUTES)
 PROCAINE WITHOUT VASOCONSTRICTOR
 2% LIDOCAINE WITHOUT VASOCONSTRICTOR
 SHORT ACTING (45-75 MINUTES)
 2% LIDOCAINE WITH 1:100,000 EPINEPHRINE
 4% PRILOCAINE WHEN USED FOR NERVE BLOCK
 MEDIUM ACTING (90-150 MINUTES)
 2% LIDOCAINE + 2% MEPIVACAINE WITH A VASOCONSTRICTOR
 4% PRILOCAINE WITH 1:200,000 EPINEPHRINE
 LONG ACTING (180 MINUTES OR LONGER)
 0.5% BUPIVACAINE 1:200,000 EPINEPHRINE

8. ACCORDING TO BIOLOGICAL SITE AND
MODE OF ACTION
CLASS A AT RECEPTOR SITE
ON EXTERNAL
SURFACE OF NERVE
MEMBRANE
BIOTOXIN
TETRODOTOXIN
CLASS B AT RECEPTOR SITE
ON INTERNAL
SURFACE OF NERVE
MEMBRANE
QUATERNARY
AMMONIUM
ANALOGUES OF
LIDOCAINE
SCORPION VENOM
CLASS C BY A RECEPTOR
INDEPENDENT
PHYSICOCHEMICAL
MECHANISM
BENZOCAINE
CLASS D BY COMBINATION
OF RECEPTOR AND
RECEPTOR
CLINICALLY USEFUL
LOCAL ANESTHETIC
AGENTS

9. MECHANISM OF ACTION
 ALTERING THE RESTING POTENTIAL OF THE NERVE
MEMBRANE
 ALTERING THE THRESHOLD POTENTIAL (FIRING LEVEL)
 DECREASING THE RATE OF DEPOLARIZATION
 PROLONGING THE RATE OF REPOLARIZATION

11. Effect of PH
 Local anesthetics are weak bases and are usually formulated as the
hydrochloride salt to render them water-soluble.
 At the chemical's pKa the protonated (ionized) and unprotonated
(unionized) forms of the molecule exist in an equilibrium but only the
unprotonated molecule diffuses readily across cell membranes.
 Once inside the cell the local anesthetic will be in equilibrium, with the
formation of the protonated (ionized form), which does not readily pass
back out of the cell. This is referred to as "ion-trapping".

12. Effect of PH
 LA are weak bases and their activity increases by increasing PH
 This because if large amount of a drug is unpolar, it will facilitate its
penetration through the cell membrane
 Once the drug has penetrated the lipid barrier and reach its site of action it
ionized and the ionized form is responsible for LA activity

13.  Acidosis such as caused by inflammation at a wound partly reduces
the action of local anesthetics.
 This is partly because most of the anesthetic is ionized and therefore
unable to cross the cell membrane to reach its cytoplasmic-facing
site of action on the sodium channel.

14.  Local anesthetics block conduction in the following order: small
myelinated axons (e.g. those carrying nociceptive impulses), non-
myelinated axons, then large myelinated axons. Thus, a differential
block can be achieved (i.e. pain sensation is blocked more readily
than other sensory modalities).

15.  Disruption of ion channel function via
specific binding to sodium channels,
holding them in an inactive state.
 Disruption of ion channel function by
the incorporation of local anaesthetic
molecules into the cell membrane .

16.  Small nerve fibres are more sensitive than large nerve fibres
 Myelinated fibres are blocked before non-myelinated fibres of the same
diameter.
 Thus the loss of nerve function proceeds as loss of pain, temperature,
touch, proprioception, and then skeletal muscle tone. This is why people
may still feel touch but not pain when using local anaesthesia.

17.  THEORIES
 THE ACETYLCHOLINE THEORY
 THE CALCIUM DISPLACEMENT THEORY
 THE SURFACE CHARGE THEORY
 THE MEMBRANE EXPANSION THEORY
 THE SPECIFIC RECEPTOR THEORY

18. CALCIUM IONS DISPLACED FROM SODIUM
CHANNEL RECEPTOR SITE
↓
LOCAL ANESTHETIC MOLECULE BINDS TO THIS
SITE
↓
BLOCKADE OF SODIUM CHANNEL
↓
DECREASE IN SODIUM CONDUCTION
↓
DEPRESSION OF RATE OF ELECTRICAL
DEPOLARIZATION
↓
FAILURE TO ACHIEVE THRESHOLD POTENTIAL
↓
LACK OF DEVELOPMENT OF ACTION POTENTIAL
↓
CONDUCTION BLOCKADE
MEMBRANE EXPANSION THEORY
SPECIFIC RECEPTOR
THEORY

19. The duration of action
 The duration of action of the drug is also related to the length of the
intermediate chain joining the aromatic and amine groups.
 Protein binding , Procaine is only 6% protein bound and has a very
short duration of action, wherease bupivacaine is 95% protein
bound. bupivacaine have a longer duration of action .

20. Absorption and distribution
 Some of the drug will be absorbed into the systemic circulation: how
much will depend on the vascularity of the area to which the drug has
been applied.
 The distribution of the drug is influenced by the degree of tissue and
plasma protein binding of the drug. the more protein bound the agent,
the longer the duration of action as free drug is more slowly made
available for metabolism.

21. Metabolism and excretion
 Esters (except cocaine) are broken down rapidly by plasma esterases
to inactive compounds and consequently have a short half life.
Cocaine is hydrolysed in the liver. Ester metabolite excretion is renal.
 Amides are metabolised hepatically by amidases. This is a slower
process, hence their half-life is longer and they can accumulate if
given in repeated doses or by infusion.

22. Adverse Effects
 CNS: excitation followed by depression (drowsiness to
unconsciousness and death due to respiratory depression.
 Cardiovascular System: bradycardia, heart block, vasodilation
(hypotension)
 Allergic reactions: allergic dermatitis to anaphylaxis (rare, but
occur most often by ester-type drugs).

23. COMPOSITION OF LOCAL ANESTHETIC
AGENT
 LIGNOCAINE 2%
 VASOCONSTRICTOR- ADRENALIN
 SODIUM META BISULPHITE 0.5mg (ANTIOXIDENT)
 METHYL PARABEN (PRESERVATION)
 THYMOL (ANTIFUNGAL)
 WATER (TO MAINTAIN VOLUME)
 NaCl (ISOTONICITY)
 PHENTOLAMINE (REVERSING AGENT)
 INSTEAD OF METHYL PARABEN- CAPRYL
HYDROCAPRINO TOXIN

24. LOCAL ANESTHETIC AGENTS
 ESTER DERIVATIVES
 PROCAINE
 DIETHYLAMINOETHYL ESTER OF PABA BY
EINHORN IN 1905
 AVAILABLE AS 4% SOLUTION
 ALSO AVAILABLE IN 2% SOLUTION IN
COMBINATION WITH 0.4% PROPOXYCAINE AND
1:30,000 LEVARTERENOL OR 1:20,000
LEVONORDEFRIN

25.  PROCAINE IS A WHITE CRYSTALLINE POWDER
 SLIGHTLY SOLUBLE IN WATER
 MOST COMMONLY USED AS HYDROCHLORIDE
SALT
 PROCAINE IS COMPARATIVELY WEAK
ANESTHETIC
 LOW DEGREE OF TOXICITY
 STANDARD OF TOXICITY AND POTENCY
 ASSIGNED A POTENCY AND TOXICITY OF 1
 PROFOUND VASODILATOR
 0.5 TO 1 gm SLOWLY OVER SUFFICIENT PERIOD

26. • PROCAINE IS HYDROLYZED TO PABA AND
DIETHYLAMINOETHANOL WITHIN THE PLASMA
• ONSET OF ANALGESIA DEPENDS ON THE
CONCENTRATION AND METHOD EMPLOYED
• WHEN INFILTRATED AROUND FREE NERVE
ENDINGS ONSET IS ALMOST IMMEDIATE
• PULPAL ANALGESIA IS ABOUT 30 MINUTES

27.  NERVOUS SYSTEM:
 READILY CROSSES THE BLOOD BRAIN BARRIER
 PRODUCES BOTH STIMULATION AND DEPRESSION OF CNS
CVS:
 DEPENDS MAINLY ON THE AMOUNT OF DRUG USED
 SYSTEMICALLY DEPRESSES SMOOTH, CARDIAC AND SKELETAL
MUSCLES
 EFFECT ON HEART IS QUINIDINE LIKE
 IN LARGE DOSES MAY PRODUCE HYPOTENSION
RESPIRATORY SYSTEM:
 LOCAL ANESTHETIC DOSE HAS LITTLE DIRECT EFFECT

28. TETRACAINE
 TETRACAINE (PARA-BUTYLAMINOBENZOYL-2-
DIMETHYLAMINOETHANOL
HYDROCHLORIDE)
 WHITE COLOURLESS POEDER
 SOLUBLE IN WATER ( 1gm IN 7 ml WATER)
 USED AS HYDROCHLORIDE SALT
 pH 5.9
 POTENT RELATIVELY TOXIC LOCAL
ANESTHETIC AGENT

29. • RAPIDLY DECOMPOSED BY ALKALI
• pKa 8.5
• COMPATIBLE WITH SULFONAMIDES AND ALL
VASOCONSTRICTORS
• AVAILABLE IN 0.15%, 1% AND 2% TOPICAL ONLY
• POPULAR FOR SPINAL ANESTHESIA
• BIOTRANSFORMATION IN THE LIVER AND END
PRODUCTS ELIMINATED BY THE KIDNEYS
• CHEMICALLY RELATED TO PROCAINE BUT
PHARMACOLOGICALLY CLOSER TO COCAINE

30.  POTENT TOPICAL ANESTHETIC WITH NO
SIGNIFICANT VASODILATION PROPERTY
 WHEN INJECTED WITHOUT A VASOCONSTRICTOR
PRODUCES 30 TO 45 MINUTES OF ANALGESIA
 SAME CONCENTRATION WITH 1:100,000
EPINEPHRINE PRODUCES 75 TO 120 MINUTES OF
ANALGESIA
 MAXIMUM DOSE: 20mg (1ml OF 2% SOLUTION)
 NON IRRITATING
 CNS AND CVS EFFECTS ARE SIMILAR TO THOSE OF
PROCAINE

31. PROPOXYCAINE
 2-DIETHYLAMINOETHYL 4-AMINO-2-
PROPOXYBENZOATE
 USED AS HYDROCHLORIDE SALT
 pH 5.5
 POTENT LOCAL ANESTHETIC
 EQUAL IN POTENCY AND TOXICITY TO
TETRACAINE
 PARTIALLY HYDROLIZED IN PLASMA
 UNDERGOES FURTHER BIOTRANSFORMATION
IN LIVER

32. • ELIMINATED BY KIDNEYS
• RAPID ONSET
• PROFOUND ANESTHESIA OF LONG DURATION
WHEN INJECTED CLOSE TO THE NERVE
SHEATH
• MAXIMUM DOSE 6.6 mg/Kg (3mg/ Ib)
• MAXIMUM TOTAL ANESTHETIC DOSAGE
SHOULD NOT EXCEED 400 mg

33. 2-CHLORPROCAINE
 BETA-DIETHYLAMINOETHYL-2-CHLORO-4-
AMINOBENZOATE
 pH 4.8
 THE SUBSTITUTION OF A CHLORIDE ATOM IN
THE BENZENE RING OF PROCAINE CAUSES A
FOURFOLD IN THE HYDROLYSIS RATE
 MORE POTENT AND LESS TOXIC THAN
PROCAINE
 RAPIDLY HYDROLYZED IN THE PRESENCE OF
PLASMA CHOLINESTERASE

34. • BYPRODUCTS ELIMINATED THROUGH KIDNEYS
• 1.2% OR 3% CONCENTRATION IS USED
• NON IRRITATING TO TISSUE
• SHORT DURATION, IT MUST BE USED WITH
VASOCONSTRICTOR
• USED IN CHILDREN
• MAXIMUM DOSE: 11mg/Kg OR 800mg (40ml OF
3% SOLUTION)

35. LIDOCAINE
 IN 1943 BY LOFGREN
 IT IS THE FIRST NON ESTER TYPE OF LOCAL
ANESTHETIC
 LIDOCAINE BASE IS ONLY SLIGHTLY WATER
SOLUBLE, THE HYDROCHLORIDE SALT IS READILY
SOLUBLE IN WATER
 IS THE STANDARD OF COMPARISION
 DIFFUSES READILY THROUGH INTERSTITIAL TISSUE
AND IN TO THE LIPID RICH NERVE

36.  RAPID ONSET OF ANESTHESIA
 pKa 7.85 FAVORS DEPROTONIZATION AND
PRODUCES UNIONIZED FREE BASE AND
PRODUCTION OF CONDUCTION BLOCK
 2 TIMES AS POTENT AND TOXIC AS PROCAINE
 ONSET TIME IS OF ABOUT 2 TO 3 MINUTES
 DURATION OF ACTION DEPENDS ON TYPE OF
INJECTION AND AMOUNT OF
VASOCONSTRICTOR

37.  NERVOUS SYSTEM:
 IN TOXIC DOSES FIRST PRODUCES STIMULATION AND THEN
DEPRESSION OF CNS
 IV LIDOCAINE IS CAPABLE OF PRODUCING A DEGREE OF
ANALGESIA AND GENERAL ANESTHESIA
 CVS:
 50 TO 100 mg (1.5 mg/Kg) GIVEN IV DURING GENERAL ANESTHESIA
AND SURGERY TO CORRECT VENTRICULAR ARRHYTHMIAS
 TOXIC DOSE : HYPOTENSION AND CARDIOVASCULAR COLLAPSE
 RESPIRATORY SYSTEM:
 SMALL DOSE HAS A MILD BRONCHODILATING EFFECT
 RESPIRATORY ARREST IS THE MOST COMMON CAUSE OF DEATH
RELATED TO OVER DOSE

38.  LIDOCAINE UNDERGOES BIOTRANSFORMATION
IN THE LIVER RATHER THAN HYDROLYSIS IN
THE PLASMA
 LIDOCAINE AND ITS BYPRODUCTS ARE
ELIMINATED BY THE KIDNEYS
 4-HYDROXY-2,6-DIMETHYLANILNINE IS THE
MAJOR URINIARY METABOLITE
 MAXIMUM DOSE: 4.4 mg/Kg (2mg/lb)

39. • NOT TO EXCEED 300mg WHEN NOT USED WITH
A VASOCONSTRICTOR
• 7mg/Kg (3.2 mg/lb)
• NOT TO EXCEED 500mg WHEN USED WITH
EITHER 1:50,000 OR 1:100,000 EPINEPHRINE
• DENTAL CARTRIDGES OF 2% LIDOCAINE ARE
AVAILABLE AND CONTAIN NO
VASOCONSTRICTOR OR EPINEPHRINE IN
CONCENTRATIONS OF 1:100,000 OR 1:50,000

40. MEPIVACAINE
 MOLECULAR WEIGHT 285.5
 WITHOUT A VASOCONSTRICTOR PULPAL
ANALGESIA OF 20 TO 40 MINUTES
 MODERATELY LONG DURATION OF ACTION
 2 TIMES AS POTENT AND TOXIC AS PROCAINE
 CURRENTLY MEPIVACAINE (COOK-WAITE
LABORATORIES), LIDOCAINE AND PRILOCAINE
(ASTRA PHARMACEUTICALS) ARE THE ONLY
DENTAL CARTRIDGES THAT DO NOT CONTAIN THE
GERMICIDE OR PRESERVATIVE METHYL PARABEN,
WHICH HAS BEEN IMPLICATED AS THE CAUSATIVE
AGENT IN MANY ALLERGIC REACTIONS

41.  IT IS A PABA DERVATIVE
 MAY ALSO BE RESPONSIBLE FOR CROSS
SENSITIVITY BETWEEN ESTER AND NON
ESTER ANESTHETIC AGENTS
 MAXIMU DOSE: WITH OR WITHOUT A
VASOCONSTRICTOR IS 6.6mg/Kg (3mg/lb)
NOT TO EXCEED 400mg
 AVAILABLE IN 3% CONCENTRATION
WITHOUT VASOCONSTRICTOR OR A 2%
SOLUTION WITH 1:20,000 LEVONORDEFRIN

42. PRILOCAINE
 DERIVATIVE OF TOLUIDINE INSTEAD OF XYLIDINE
 EMPIRICAL FORMULA OF BASE : C13H20N20
 MOLECULAR WEIGHT: 220.3
 HYDROCHLORIDE SALTS ARE USED HAVING
EMPIRICAL FORMULA OF C13H21Cl N20
 CONTAINS 86% BASE AND HAVING A MOLECULAR
WEIGHT OF 256.8

43.  4% SOLUTION OF PRILOCAINE HAS A PH of 6.0 – 7.0
 pKa is 7.9
 ABOUT 40% LESS TOXIC THAN LIDOCAINE
 UNDERGOES BIOTRANSFORMATION MORE RAPIDY
THAN LIDOCAINE
 ORTHOTULUIDINE A METABOLITE PRODUCES
METHEMOGLOBIN IN LARGE DOSES
 CONTRAINDICATED IN PATIENTS WITH
CONGENITAL OR IDIOPATHIC
METHEMOGLOBINEMIA

44. • 400mg PRODUCES A METHEMOGLOBIN LEVEL
OF ONLY ABOUT 1% IN THE BLOD
• LEVELS LESS THAN 20% RARELY PRODUCE
SYMPTOMS
• SYMPTOMS INCLUDE: CYANOSIS COUPLED
WITH RESPIRATORY OR CIRCULATORY DISTRESS
• SYMPTOMS MAY BE REVERSED WITH IV
ADMINISTRATION OF 1-2mg/Kg OF 1%
METHYLENE BLUE

45.  AVAILABLE IN 4% SOLUTION WHICH WITHOUT
EPINEPHRINE GIVES 60 MINUTES OF WORKING
ANESTHESIA
 WHEN EPINEPHRINE IN A 1:200,000
CONCENTRATION IS ADDED TO 4% CITANEST THE
PRODUCT IS CALLED CITANEST FORTE
 DURATION OF PULPAL ANALGESIA IS ABOUT 60-90
MINUTES


46. BUPIVACAINE
 CRYSTALLINE POWDER FREELY SOLUBLE IN 95% ETHANAL
AND WATER AND SLIGHTLY SOLUBLE IN CHLOROFORM OR
ACETONE
 PH 4.5-6.5 AND pKa IS 8.1
 AMIDE DERIVATIVE STRUCTURALLY SIMILAR TO
MEPIVACAINE WITH A BUTYL GROUP REPLACING THE
METHYL GROUP IN THE HYDROPHYLIC END
 MARCAINE: BUPIVACAINE, 0.5% WITH 1:200,000
EPINEPHRINE AVAILABLE IN CONVENTIONAL 1.8 ml
CARTRIDGE
 ALSO SUPPLIED IN 10, 2O AND 50 ml VIALS CONTAINING
0.25%, 0.5% OR 0.75% SOLUTION WITHOUT A
VASOCONSTRICTOR OR WITH 1:200,000 EPINEPHRINE

47. • STRUCTURAL MODIFICATION HAS RESULTED IN THE
PRODUCTION OF AN AGENT THAT HAS 35 FOLD INCREASE
IN OIL WATER PARTITION COEFFICIENT PLUS A SIGNIFICANT
INCREASE IN PROTEIN BINDING QUALITIES
• THE NET EFFECT IS A 4 FOLD INCREASE IN INTRINSIC
ANESTHETIC ACTIVITY AND DURATION OF ACTION
• IT IS 4 TIMES AS POTENT AND TOXIC AS MEPIVACAINE AND
LIDOCAINE
• PULPAL ANESTHESIA IS INCREASED TO 3 HOURS
• DURATION OF SOFT TISSUE ANESTHESIA MAY EXTEND TO 12
HOURS

48. • A PERIOD OF ANELGESIA PERSISTS AFTER THE RETURN OF
OTHER SENSATIONS, HENCE THE NEED OF ANALGESIC DRUG
IS REDUCED OR ELIMINATED
• SHOULD NOT BE ADMINISTERED TO CHILDREN
 UNDERGOES BIOTRANSFORMATION IN LIVER BY
CONJUGATION WITH GLUCURONIC ACID.
 TOTAL DOSE IN HEALTHY ADULT SHOULD NOT EXCEED
2mg/Kg (0.9mg/lb)NOT TO EXCEED 225 mg WITH 1:200,000
EPINEPHRINE OR 175 mg WITHOUT A VASOCONSTRICTOR
 TOTAL DOSE MAY BE REPEATED UPTO ONCE EVERY 3 HOURS
NOT TO EXCEED 400 mg IN 24 HOURS

49. ETIDOCAINE
 WHITE CRYSTALLINE POWDER FREELY SOLUBLE IN
95% ETHANAL AND WATER
 PH IS 3-5 AND pKa IS 7.7
 AMIDE DERIVATIVE, STRUCTURALLY SIMILAR TO
LIDOCAINE, WITH A PROPYL FOR AN ETHYL GROUP
AT THE AMINE END AND THE ADDITION OF AN ETHYL
GROUP AT THE ALPHA CARBON IN THE
INTERMEDIATE CHAIN
 PRESENTLY NOT AVAILABLE IN A DENTAL CARTRIDGE
 IT SUPPLIED IN 30 AND 50 ml VIALS CONTAINING
0.5% OR 1% SOLUTION OF ETIDOCAINE WITHOUT A
VASOCONSTRICTOR OR WITH 1:200,000 EPINEPHRINE

50. • A 20ml VIAL CONTAINING 1.5% ETIDOCAINE WITH
1:200,000 EPINEPHRINE IS ALSO AVAILABLE
• 50 FOLD INCREASE IN OIL WATER PARTITION COEFFICIENT
AND ALMOST 2 TIMES PROTEIN BINDING CHARACTERISTICS
• FASTER ONSET AND LONGER DURATION
• 4 TIMES INCREASE IN ANESTHETIC ACTIVITY AND 2 TIMES
LONGER DURATION OF ACTION THAN LIDOCAINE
• NOT ADMINISTERED TO CHILDREN

51.  TWICE AS TOXIC AS LIDOCAINE
 TOTAL DOSE SHOULD NOT EXCEED 4mg/Kg (1.8mg/lb) TO A
MAXIMUM OF 300 mg WHEN USED WITHOUT A
VASOCONSTRICTOR
 4.4mg/Kg (2mg/lb) TO A MAXIMUM OF 400mg WHEN
COMBINED WITH 1:200,000 EPINEPHRINE
 INCREMENTAL DOSE MAY BE REPEATED EVERY 2 TO 3
HOURS

52. TOPICAL ANESTHETICS
 DIRECT APPLICATION TO ABRADED SKIN OR
TO THE MUCOUS MEMBRANE SURFACE
 PORELY SOLUBLE IN WATER AND DO NOT
FORM SOLUBLE ACID SALTS
 MOST COMMON EXCEPTIONS ARE
LIDOCAINE AND TETRACAINE
 LIDOCAINE 5% OR 10%
 TETRACAINE 1% OR 2%
 HIGHER CONCENTRATIONS ARE REQUIRED
FOR DIFFUSION THROUGH MUCOUS
MEMBRAN

53. • IN ADDITION THE MOST COMMONLY USED TOPICAL
ANESTHETICS ARE BENZOCAINE (ETHYL AMINOBENZOATE)
AND BENZYL ALCOHOL
• WATER INSOLUBLE TOPICAL ANESTHETICS
• SOLUBLE IN VEHICALS SUCH AS ALCOHOL, POLYETHYLENE
GLYCOL, PROPYLENE GLYCOL OR
CARBOXYMETHYLCELLULOSE THAT MAKES THEM
AMENABLE TO SURFACE APPLICATION
• POORLY ABSORBED AND SYSTEMIC TOXICITY VIRTUALLY
UNKNOWN

54. BENZOCAINE
 CLOSELY RELATED TO PROCAINE
 ESTER OF AMINOBENZOIC ACID
 NO BASIC NITROGEN GROUP, HENCE UNABLE
TO FORM SOLUBLE ANESTHETIC SALTS
 HURRICAINE CONTAINS BENZOCAINE
 IRRITATING IF INJECTED IN TO TISSUE
 CAN PRODUCE TOXIC SYMPTOMS IF
ABSORBED IN SUFFICIENT QUANTITIES

55. LIDOCAINE
 AVAILABLE IN TWO FORMS: LIDOCAINE BASE
LIDOCAINE
HYDROCHLORIDE
 LIDOCAINE BASE
 INSOLUBLE IN WATER
 5% CONCENTRATION
 EXCELLENT SURFACE ANESTHESIA WITHIN 15 SECONDS OF
APPLICATION
 SINGLE APPLICATION HAS A DURATION OF ABOUT 30
MINUTES
 POORLY ABSORBED, SYSTEMIC TOXICITY IS NEGLIGIBLE
 10% LIDOCAINE BASE IN AN AEROSOL SPRAY WITH A
METERED DOSE VALVE DISCHARGES 10mg PER SPRAY ALSO

56. WATER SOLUBLE TOPICAL ANESTHETICS
 PRIMARY DISADVANTAGE: RAPID ABSORPTION IN TO
BLOOD STREAM
 BENZYL ALCOHOL
 AROMATIC ALCOHOL SOLUBLE IN WATER
 VERY IRRITATING ON INJECTING INTO THE TISSUES
 4% TO 10% SOLUTIONS
 SHORT ACTING
 LESS TOXIC THAN ETHYL AMINOBENZOATE

57. TETRACAINE HYDROCHLORIDE
 VERY POTENT
 HIGHLY WATER SOLUBLE
 ONSET OF ACTION IS SLOW BUT DURATION IS RELATIVELY
LONG LASTING (45 MINUTES TO 1 HOUR)
 FREQUENTLY COMBINED WITH BENZOCAINE, AN AGENT
OF RAPID ONSET AND BRIEF DURATION
 A MIXTURE OF BENZOCAINE 14%, BUTAMBEN 2% AND
TETRACAINE 2% DISSOLVED IN DIPROPYLENE GLYCOL
UNDER THE NAME CETACAINE IS EXTENSIVELY USED
 MAXIMUM DOSE: 20 mg OR 1 ml OF 2% SOLUTION

58. LIDOCAINE HYDROCHLORIDE
 2% OR 4% CONCENTRATION
 MAXIMUM RECOMMENDED DOSE IS 200mg
 WHEN APPLIED BY MEANS OF COTTON APPLICATORS THE
SUGGESTED MAXIMUM DOSE IS 1 TO 5 ML (40 TO 200MG)
OR 0.6 TO 3 mg/Kg (0.3 TO 1.5 mg/lb) NOT TO EXCEED
300mg OR 4.5mg/kg

59. VASOCONSTRICTORS

60.  THE VASOCONSTICORS COMMONLY USED IN DENTAL
LOCAL ANESTHETIC SOLUTIONS CAN BE DIVIDED INTO THE
FOLLOWING 3 GROUPS
1. PYROCATECHINE DERIVATIVES- EPINEPHRINE AND
NOREPINEPHRINE
2. BENZOL DERIVATIVE- LEVONORDEFRIN
3. PHENOL DERIVATIVE- PHENYLEPHRINE

61. MODE OF ACTION
SYMPATHOMIMETICS AMINES ACT BY
1. ATTACHING TO AND DIRECTLY STIMULATING ADRENERGIC
RECEPTORS
2. ACTING INDIRECTLY BY PROVOKING THE RELEASE OF
ENDOGENOUS CATECHOLAMINES
3. A COMBINATION OF DIRECT AND INDIRECT ACTION
ALL VASOCONSTRICTORS USED IN CONJUNCTION WITH
LOCAL ANESTHETICS ARE DIRECTLY ACTING AGENTS

62. EPINEPHRINE
 LEVOROTATORY ALKALOID SECRETED BY ADRENAL
MEDULLA
 HIGHLY SOLUBLE IN WATER
 MOST POTENT VASOCONSTRICTOR USED
 USED AS STANDARD OF COMPARISON
 HAS A PRESSOR POTENCY OF ONE
 CONCENTRATIONS FROM 1:50,000 TO 1:250,000 ARE USED

63. CVS:
BETA1 STIMULATION RESULTS IN AN INCREASE IN HEART RATE
(POSITIVE CHRONOTROPIC EFFECT)
INCREASE IN STROKE VOLUME, CARDIAC OUTPUT AND
OXYGEN CONSUMPTION
INCREASED IRRITABILITY OF MYOCARDIUM- PREMATURE
VENTRICULAR CONTRACTIONS AND TACHYCARDIAS
OTHER EFFECTS: INCREASED BLOOD GLUCOSE LEVELS,
INCREASED GLYCOGENOLYSIS AND PUPILLARY DILATION

64. NOREPINEPHRINE
 MAJOR PRESSOR AMINE FOUND IN THE
POSTGANGLIONIC ADRENERGIC NERVE
 WHITE CRYSTALLINE SALT, FREELY SOLUBLE IN WATER
WITH A PH OF 3.4
 IT HAS NO RADICAL ON THE AMINO GROUP
 ACTS PREDOMINANTLY ON THE ALPHA RECEPTOR SITE
 DOSE SHOULD NOT EXCEED 0.34mg OR 10ml OF
SOLUTION CONTAINING 1:30,000

65. LEVONORDEFRIN
 IT IS ONE FIFTH AS ACTIVE AS EPINEPHINE
 LOWER SYSTEMIC TOXICITY
 IT ACTS DIRECTLY AND ALMOST EXCLUSIVELY ON THE
ALPHA RECPTOR SITES
 DOSE: WHEN 1:10,000 CONCENTRATION IS USED IT
SHOULD BE LIMITED TO A TOTAL DOSE OF 1mg
 PATIENTS WITH CARDIAC CONDITIONS ITS USE SHOULD
BE LIMITED TO A MAXIMUM OF 0.4mg

66. PHENYLEPHRINE
 SIMILAR TO EPINEPHRINE BUT DIFFERING STRUCTURALLY .
 IT HAS ONLY ONE HYDROXYL GROUP ON THE BENZENE
RING
 IT IS THE MOST STABLE AND WEAKEST OF ALL
VASOCONSTRICTORS AND LONG LASTING
 USED IN CONCENTRATIONS 10 TO 20 TIMES THOSE OF
EPINEPHRINE: 1:2,500
 IT IS A PURE ALPHA RECEPTOR AGONIST
 DOSE: 1:2,500 LIMITED TO 4mg AT ONE TIME
 IN PATIENTS WITH CARDIAC CONDITIONS : REDUCED TO 1.6
mg

67. TERMINATION OF ACTION AND
POTENTIAL DRUG INTERACTION
 TRICYCLIC ANTIDEPRESSANTS INTERFERE WITH THE
REUPTAKE MECHANISM
 DEACTIVATION BY EXTRANEURONAL ENZYME (CATECHOL-
O-METHYL TRANSFERASE)
 UPTAKE BY BLOOD SYSTEM
 INTRANEURONAL ENZYME DESTRUCTION (MONOAMINO
OXIDASE)
 MAO I INHIBITOR
 ALPHA ADRENERGIC BLOCKERS: PHENOTHIAZINE
 EPINEPHRINE REVERSAL EFFECT
 BETA ADRENERGIC BLOCKERS (PROPRANOLOL, INDERAL)

68. SELECTION OF VASOCONSTRICTORS
1. DURATION OF DESIRED EFFECT
2. PHYSICAL CONDITION OF THE PATIENT
3. DESIRE TO PRODUCE HEMOSTASIS
4. CONCURRENT MEDICATION

69. Properties of ideal LA
 Reversible action.
 Non-irritant.
 No allergic reaction.
 No systemic toxicity.
 Rapid onset of action.
 Sufficient duration of action.
 Potent.
 Stable in solutions.
 Not interfere with healing of tissue.
 Have a vasoconstrictor action or compatible with VC.
 Not expensive

70. CONCLUSION

73. Mechanism of action
- Inhibiting excitation of nerve endings or blocking
conduction in peripheral nerves. Binding to and inactivating
sodium channels.
- Local Anaesthetics are alkaloid bases that are combined with
acids, usually hydrochloric, to form water soluble salts. All
anaesthetic salts are formed by a combination of weak base
and a strong acid. The salts are used because they are
stable and soluble in water; water solubility isnecessary for
their diffusion through interstitial fluids to the nerve fibers.

74. - Sodium influx through these channels is necessary for the
depolarization of nerve cell membranes and subsequent propagation
of impulses along the course of the nerve.
- when a nerve loses depolarization and capacity to propagate an
impulse, the individual loses sensation in the area supplied by the
nerve

75. - block nerve fiber conduction by acting on nerve membranes
- inhibit sodium ion activity
- blocks depolarization--> blocks nerve conduction

76.  When the influx of sodium is interrupted, an action potential cannot
arise and signal conduction is inhibited. LA drugs bind more readily
to sodium channels in activated state, thus onset of neuronal
blockade is faster in neurons that are rapidly firing. This is referred
to as state dependent blockade.