PCO 501
LOCAL ANAESTHETICS
Ms. Funmilayo Adeniyi
DEPT OF PHARMACOLOGY & TOXICOLOGY,
COLLEGE OF PHARMACY, ABUAD 1
WHAT ARE LOCAL
ANAESTHETICS?
• Local anaesthetics (LAs) are drugs which cause reversible loss
of sensory perception, especially of pain, in a restricted area
of the body upon topical application or local injection.
• They block generation and conduction of nerve impulse at
any part of the neuron without causing any structural
damage.
• Local anesthetics produce a transient and reversible loss of
sensation (analgesia) in a restricted region of the body
without loss of consciousness.
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CLASSIFICATION OF LOCAL
ANESTHETICS
• Local anaesthetics can be classified as:
• Esters & amides.
• The ester-type anesthetics, contain an ester linkage in their
structure.
• In contrast, the amide-type agents, contain an amide linkage.
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CLASSIFICATION OF LOCAL ANESTHETICS
Esters Amide
• Benzocaine • Bupivacaine
• Procaine • Lidocaine/Lignocaine
• Proparacaine • Levobupivacaine
• Mepivacaine
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Structure of local anaesthetics
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Mechanism of action of local
anaesthetics
• Local anesthetics stop axonal conduction by blocking sodium
channels in the axonal membrane. By blocking axonal sodium
channels, local anesthetics prevent sodium entry, and
thereby blocking conduction.
• The LAs block nerve conduction by decreasing the entry of
Na+ ions during upstroke of action potential (AP). As the
concentration of the LA is increased, the rate of rise of Action
potential and depolarization decreases causing slowing of
conduction and blockage of conduction. 6
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Absorption
• Local anesthetics are absorbed into the blood and become
distributed to all parts of the body. The rate of absorption is
determined largely by blood flow to the site of administration.
• Many factors influence entry of local anaesthetics into the
circulation:
• Vasodilating ability of the drug.
• Volume and concentration.
• Vascularity of the tissues.
• The route of administration.
• The presence of vasoconstrictor.
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PHARMACOKINETICS DURATION OF ACTION
• Effective within 5 min • Duration = protein binding
• Duration of action – 1-1.5 h
• Bupivacaine 95%
• Activity is Ph dependent
Lidocaine 65%
• Increased action in acidic
pH
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Metabolism
• The process by which a local anesthetic is metabolized depends
on the class—ester or amide—to which it belongs.
• Ester-type local anesthetics are metabolized in the blood by
enzymes known as esterases.
• In contrast, amide-type anesthetics are metabolized by enzymes
in the liver.
• For both types of anesthetic, metabolism results in inactivation.
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Ester type drugs
• Cocaine: is the first and most potent local anaesthetic agent, rarely used
because of the problems of misuse. Cocaine is an excellent local anesthetic.
• Administered topically, the drug is employed for anesthesia of the ear, nose, and
throat. Anesthesia develops rapidly and persists for about an hour.
• Unlike other local anesthetics, cocaine causes intense vasoconstriction (by
blocking norepinephrine uptake at sympathetic nerve terminals on blood
vessels).
• In addition to causing local anesthesia, cocaine has pronounced effects on the
sympathetic and central nervous systems. These sympathetic and CNS effects
are due largely to blocking the reuptake of norepinephrine by adrenergic
neurons. Half life 30 minutes.
• Dosage: Used as topical 4 – 10% solution
Maximum dose is 1.5 mg/kg – 100mg max.
• Used intranasally during apical surgery. 11
Ester type drugs
• Procaine:
• For many years, procaine was the preferred injectable local
anesthetic. However, with the development of newer agents, use
of procaine has sharply declined. It is rarely used.
• The only indication for its use in dentistry is in patients with
proven allergy to the amide group.
• Used intra-arterially, as part of the recognized regimen, to treat
the arteriospasm which might occur during intravenous sedation.
• It has an excellent vasodilatory properties. 12
Ester type drugs
• Procaine continuation
• The drug is not effective topically, and must be given by injection.
Administration in combination with epinephrine delays absorption.
• Onset & duration of Action:
• Procaine has a very shot duration (5 minutes) and a long onset
time of 10 minutes
• Dosage:
• The maximum dose is 6 mg/kg, 400 mg max.
• Used as 2% with 1:80 000 epinephrine to increase efficacy.
• Metabolism:
• Procaine is rapidly by plasma esterase.
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Ester type drugs
• Benzocaine:
• Used mainly as topical, due to its poor water solubility, and
because of its low toxicity, it is used in concentration up to 20%.
• Hydrolyzed rapidly by plasma esterase to p-aminobenzoic acid
accounting for its low toxicity.
• Topical benzocaine can cause methemoglobinemia. Most cases
were in children under 2 years of age treated with benzocaine gel
for teething pain. Because of this risk, topical benzocaine should
not be used in children younger than 2 years of age without
medical advice. It should be used with caution in children and
adults. 14
Metabolism of Ester drugs
• They are metabolized in plasma by pseudocholinesterase
enzyme, and some in the liver.
• People, who lack the enzyme, are at risk of an overdose by the
ester type local anaesthetics.
• Para-aminobenzoic acid (PABA) is the major metabolite of ester
with no anaesthetic effect.
• It is the agent responsible for ester allergies.
• Rapid metabolism: procaine half-life is 2 minutes
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Amide type drugs
• Lignocaine (Lidocaine):
• Synthesized in 1943 and used in dentistry since 1948 and is also known as
Xylocaine.
• Lidocaine can be administered topically and by injection.
• Anesthesia with lidocaine is more rapid, more intense, and more prolonged
than an equal dose of procaine.
• Effects can be extended by coadministration of epinephrine.
• It highly lipophilic (partition coefficient 3) , rapidly absorbed.
• Has half-life (t0.5) of 90 minutes
• Metabolized only in the liver and its metabolites are less toxic with no
action.
• If plasma levels of lidocaine is too high, CNS and cardiovascular toxicity 16can
Lignocaine (Lidocaine)
continuation
• Lidocaine hydrochloride [Xylocaine, others] is available in several
formulations (cream, ointment, jelly, solution, aerosol, patch) for
topical administration.
• Dosage:
• 4.4 mg/kg – 300 mg max
• Used as 2% plain or with 1:80 000 epinephrine
• 4 and 10% spray, 2% gel and 5% ointments.
• Onset & duration of action
• Rapid onset 2 – 3 minutes
• Short duration (10 minutes)
• With epinephrine- intermediate duration (45 – 60 minutes) 17
Amide type drugs
• Prilocaine:
• A very potent local anaesthetic and is less toxic than
Lignocaine.
• It produces less vasodilatation than lignocaine
• Rate of clearance is higher than other amide-types, suggesting
extra-hepatic metabolism with relatively low blood
concentration.
• It’s metabolite o-toluidine lead to methaemo-globinaemia
(more than 600 mg in adults)
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Amide type drugs
• Used either plain 4% or 3% combined with 0.03IU/mL of
Felypressin as vasoconstrictor.
• Onset & Duration:
• Slower onset – 4 minutes.
• It’s duration of action is similar to Lignocaine.
• Dosage;
• 6.0 mg/kg – max. 400 mg.
• Combined with Lignocaine as a topical anaesthetic agent to be
used prior to vene-section and during dental sedation in
children.
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Amide type drugs
• Mepivacaine:
• Possess the least vasodilating effect.
• Metabolized in the liver and has t0.5 of 120 minutes.
• It’s main indication is when local anaesthetic without
vasoconstrictor is needed. 3% plain is more effective than
lignocaine.
• Onset & duration:
• Rapid onset but slightly shorter duration.
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Amide type drugs
• Bupivacaine:
• A long-acting local anaesthetic agent, with a t0.5 of 160 minutes
due grater binding capacity to plasma protein and tissue proteins
• Metabolized in the liver.
• Used mainly in Oral surgical procedures for its long-lasting pain
control.
• Longer onset and longer duration (Regional 6 – 8 hors)
• Dosage:
• 1.3 mg/kg – Max 90 mg
• 0.25 – 0.75% with or without adrenaline 1:200 000
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Amide type drugs
• Etidocaine:
• A long-acting agent similar to Bupivacaine but with faster onset.
• Metabolized in the liver.
• Dosage:
• 8 mg/kg – Max 400 mg
• 1.5% with 1:200 000 epinephrine.
• Lignocaine is the most common used agent both topically
and by injection as 2% with or without adrenaline, with a
maximum dose of 4.4 mg/kg.
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Metabolism of Amide type drugs
• Amide Drugs:
• They are metabolized in the liver, except Prilocaine which undergo
some biotransformation in the kidney and lungs.
• Some of the metabolites possess local anaesthetic and sedative
properties.
• Normal local anaesthetic dose in patient with impaired liver function
will result in relative overdosage.
• Old age patient shows reduction in liver function. Reduce dose in old
patients.
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SYSTEMIC EFFECTS OF LOCAL ANAESTHETICS
CNS EFFECTS
• Cocaine is a powerful CNS stimulant causing sequence of euphoria,
excitement, mental confusion, restlessness, tremor and twitching of
muscles.
• At safe clinical doses, they produce little CNS effects. Higher dose or
accidental i.v. injection produces CNS stimulation followed by depression.
• Others include convulsion, unconsciousness, respiratory depression and
death, in a dose-dependent manner.
• Neurological symptoms of lidocaine overdose and other LAs are circumoral
numbness, abnormal sensation in the tongue, dizziness, blurred vision,
tinnitus followed by drowsiness, dysphoria and lethargy.
• Higher doses produce excitation, restlessness, agitation, muscle twitching,
seizures and finally unconsciousness 24
Cardiovascular System
• LA’s suppress excitability in the heart myocardium and conducting
system.
• They can cause bradycardia, heart block, reduced contractile force,
and even cardiac arrest.
• LAs are cardiac depressants, but not significant effects are observed
at conventional doses.
• At high doses they decrease automaticity, excitability, contractility,
conductivity and prolong effective refractory period (ERP).
• They have a quinidine like antiarrhythmic action.
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Allergic Reactions
• An array of hypersensitivity reactions, ranging from allergic dermatitis
to anaphylaxis, can be triggered by local anesthetics.
• Patients allergic to one ester-type anesthetic are likely to be allergic to
all other ester-type agents.
• Fortunately, cross-hypersensitivity between the esters and amides has
not been observed.
• Therefore, the amides can be used when allergies contraindicate use
of ester-type anesthetics.
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Blood vessels
• In blood vessels, anesthetics relax vascular smooth muscle.
• The resultant vasodilation can cause hypotension.
• The cardio-suppressant actions of one local anesthetic—lidocaine—
are used to treat dysrhythmias.
Use in Labor and Delivery
• Local anesthetics can depress uterine contractility and prolong labor.
• Also, local anesthetics can cross the placenta, causing bradycardia
and CNS depression in the neonate.
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Adverse effect of local
anaesthetics
• CNS effects are light-headedness, dizziness, auditory and visual disturbances,
mental confusion, disorientation, shivering, twitchings, involuntary movements,
finally convulsions and respiratory arrest.
• This can be prevented and treated by diazepam/midazolam.
• Cardiovascular toxicity of LAs is manifested as bradycardia, hypotension,
cardiac arrhythmias, asystole and vascular collapse.
• Injection of LAs may be painful, but local tissue toxicity of LAs is low. However,
wound healing may be sometimes delayed. Addition of vasoconstrictors
enhances the local tissue damage; rarely necrosis results.
• Vasoconstrictors should not be added for ring block of hands, feet, fingers,
toes, penis and in pinna.
• Bupivacaine has the highest local tissue irritancy.
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