This presentation gives you a detail information about the Local Anesthetics and its history, mechanism of action, Pharmacological action along with its indication and adverse effect. It also contains the information about techniques used for Injecting Local Anesthesia.

1. Dr. Rajendra Gode Institute of Pharmacy, Amravati
Drugs acting on PNS (Somatic)-
Local Anesthetics
Presented by
Shraddha S. Raut
M. Pharm (Pharmacology) 1
Guided by
Dr. Prashant Ajmire
M. Pharm, Phd, (Pharmacology)

2.  Contents
Introduction
Properties for ideal LAs
History
Chemistry
Classification
Mechanism of action
Pharmacodynamic
Pharmacokinetic
Adverse effects
Individual agents
Uses and techniques of LAs
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3.  Introduction
Pain : Pain is an unpleasant sensory experience to us that something hurts.
Anesthetics : Drugs used to induce anesthesia causing temporary loss of sensation.
Local Anesthetics : Drugs which upon topical application or local injection causes
reversible loss of sensory perception in a restricted area of body.
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Types of anesthetics
General anesthetics Local anesthetics

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 Properties of Ideal LAs
1) Non-irritating to the tissue
2) Should be effective whether injected or applied topically
3) Rapid onset of action
4) It should not cause allergic reactions
5) Duration of action must be long enough to complete the procedure
6) Should not cause loss of consciousness
7) Should not causes structural damage to the nerve
8) Should be sterile

5.  History
5
• In 19th century, coca leaves (Erythroxylum coca) have
been chewed for their stimulatory and euphoric action.
• Albert Niemann – in 1860, isolated cocaine from coca
leaves, he tasted it and noted its numbing effect on mouth
and tongue.
• Sigmund Freud – studied cocaine’s physiological action
• Carl Koller – introduced cocaine as topical anesthetic
for ophthalmological surgery
• In 1905, a synthetic substitute Procaine was discovered.
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 Chemistry
Local Anesthetics
Aromatic
group
Ester/Amide
group
Basic side
chain
+ +
(hydrophilic)
(hydrophobic)
consists of 3 parts
1 3
2
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• LAs consists of 3 parts responsible for
Aromatic group - Penetration
Absorption
Ester/Amide group - Metabolism
Elimination
Basic side chain - MOA
• All LAs are weak bases with amphiphilic
property, hence ionizes at physiological pH.
• It is able to penetrate axon membrane and
nerve sheath only in unionized form.

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 Classification
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• On the basis of linkage LAs are also classified as -
Conti…….
Local Anesthetics
Ester-linked LAs Amide-linked LAs
Lidocaine
Bupivacaine
Dibucaine
Prilocaine
Ropivacaine
Cocaine
Procaine
Chlorprocaine
Tetracaine
Benzocaine
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 Mechanism of action
• LAs prevents both generation and conduction of nerve impulse by decreasing the entry
of Na+ ions during upstroke of action potential.
• Increase in concentration of LA leads to
decrease in the rate of action potential generation
decrease in the maximum depolarization
• Finally depolarization fails to reach the threshold potential.
• The LAs acts by interacting with the receptor situated within the voltage sensitive Na+
channel and thereby interrupting the impulse conduction.
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Conti…..
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BH+
BH
+
B- H+

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Conti……
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 Pharmacodynamic
• LAs shows two kinds of actions – Local action and Systemic action
• Local Actions
1) They blocks sensory nerve endings, neuromuscular junction and ganglionic receptors.
2) They reduces release of Ach from motor nerve endings.
3) LAs are also used for pain relief of perineum stretching in normal labour.
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Conti…..
• Systemic Actions
 CNS
a. It causes sequence of stimulation followed by depression.
b. Dysphoria, muscle twitches, restlessness, tremors, convulsions.
c. In high dose, it causes respiratory depression and death.
 CVS
a. Heart - Conductivity, Excitability, Contractility, Conductivity
effective refractory period
High plasma conc. of LAs causes prolonged QT interval
b. Blood Vessels - BP by sympathetic blockade
Cocaine - local vasoconstriction and BP

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 Pharmacokinetic
• Surface anesthetics are rapidly absorbed from mucous membrane.
• Rate of absorption depends upon the blood flow to the area of application or
injection.
• LAs are widely distributed and rapidly enters highly perfused organ.
• Ester linked LAs - rapidly hydrolyzed by Esterases in liver.
• Amide linked LAs - degraded only in liver microsomes (CYP450) by dealkylation
and hydrolysis.
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 Adverse effects
CNS Effects Hypersensitivity
reactions
Cardiovascular
toxicity
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 Individual agents
Pharmacology of Procaine
• Procaine is a benzoic acid derivative and most commonly
used in dental procedure to numb the area around the tooth.
• It has slow onset and short duration of action.
Bioavailability NA
Protein binding NA
Half-life 7.7 min
Metabolism Hydrolysis by plasma pseudocholinesterase
Route of elimination Urine
Dose 1–2% Topical
• Pharmacokinetic
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• Adverse Drug Reaction - Hypersensitivity
Restlessness and shaking
Weakening of myocardium leading to cardiac arrest
• Contraindications
a. In cases of septicemia and cerebrospinal diseases such as meningitis
b. It should be undertaken cautiously in patients with cardiac arrythmia and asthma
• Indications
a. Used as LA in oral surgery
b. Used in dental procedure like tooth extraction, root canal and cavity filling
c. Co-administered with intramuscular penicillin for treatment of syphilis, pneumococcal
pneumonia, scarlet fever, pharyngitis and rheumatic fever

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Pharmacology of Lidocaine
• Lidocaine, also known as Lignocaine is a synthetic amino-
ethyl amide.
• It is commonly used for local and topical anesthesia.
Bioavailability 35 % orally, 3 % topical
Protein binding 60 - 80 %
Half-life 1.5 - 2 hrs.
Metabolism 90 % in liver by CYP3A4
Route of elimination Urine
Dose 0.5 - 2 % topical
• Pharmacokinetic
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• Adverse Drug Reaction
Drowsiness, mental clouding, dysphoria, altered taste, tinnitus
Overdose can cause muscle twitching, convulsion, fall in BP, coma
• Contraindications
a. In heart block
b. In severe sinoatrial block
• Indications
a. Used as local numbing agent
b. Intravenous lidocaine is used as a second-line treatment for neonatal seizures
c. Inhaled lidocaine can be used as a Cough suppressor
d. Lidocaine along with ethanol, acetic acid and ammonia may also help in treating
jellyfish sting.

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Pharmacology of Bupivacaine
• Bupivacaine is more lipophilic and more potent long-acting
amide-linked LA.
• It is used for infiltration, epidural and spinal anesthesia.
Bioavailability NA
Protein binding > 95 %
Half-life 2.7 hrs. (adult), 8.1 hrs. (neonates)
Metabolism In liver by CYP450 3A4
Route of elimination Urine
Dose Vary as per type
• Pharmacokinetic
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• Adverse Drug Reaction
CNS : facial tingling, vertigo, tinnitus, anxiety, dizziness, coma, seizure
CVS : hypotension, arrythmia, bradycardia. Cardiac arrest, heart block
• Contraindications
a. G6PD deficiency
b. Methemoglobinemia
c. Atrioventricular heart block
• Indications
a. Used for producing local or regional anesthesia for oral surgery
b. Used during obstetrics
c. Used to give postoperative pain relief

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 Uses and techniques of LAs
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Surface Anesthesia
Infiltration anesthesia
Conduction block
Spinal anesthesia
Epidural anesthesia
Intravenous regional anesthesia
1
2
3
4
5
6

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Surface Anesthesia
1
• The topical application of LAs are used to anesthetize skin,
mucous membrane or cornea.
• LAs can be applied to skin to treat Pruritus (itching) caused
by insect bites, poison ivy and eczema.
• Onset and duration depends on site, drug, its concentration
and form. Ex: Lidocaine
Infiltration Anesthesia
2
• Dilute solutions of LA is infiltrated under the skin to block
sensory nerve endings.
• It is used in minor operations like incision, hydrocele, etc.
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Conduction block
3
• LA is injected around the nerve trunks so that the area distal to injection is anesthetized
and paralyzed.
a) Field block
• It is produced by injecting the LA subcutaneously in a manner that all nerves coming to
a particular field are blocked.
• It is used for appendicectomy, dental procedure, scalp stitching, operation on fore arms
and legs, etc.
b) Nerve block
• It is produced by injecting LA around appropriate nerve trunks.
• Muscles supplied by the nerve can be paralyzed.
• It is used for lingual, ulnar, femoral, facial area.
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Spinal anesthesia
4
• The LA is injected in subarachnoid space between L2-L3 or
L3-L4 below the spinal cord.
• The lower abdomen and hind limbs are anesthetized and
paralyzed.
• The level of anesthesia depends on volume and speed of
anesthesia.
• Spinal anesthesia is used in operation of lower abdomen,
lower limbs and pelvis.
• Advantages of SA over GA are -
a. It is safer
b. Produces good analgesia and muscle relaxation
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Epidural anesthesia
5
• The LA is injected in epidural space which acts primarily on nerve roots.
• It is divided into 3 categories depending on site of injection.
Epidural Anesthesia Region of injection Used in
Thoracic Mid-thoracic region Upper abdominal
surgery
Lumbar Lumbar region Operation of –
Lower abdomen
Pelvis
Hind limb
Sacral Sacral canal Vaginal delivery
Genitourinary
operation
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Intravenous regional anesthesia
5
• The LA is injected in distal vein of tourniquet occluded limb.
• The safety of procedure depends upon rapid uptake of LA by peripheral tissues.
• It is mainly used for upper limb and orthopedic procedure.
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 References
1) Essentials of Medical Pharmacology, 8th Edition by KD Tripathi, Pg no. 386-397
2) Rang and Dale's Pharmacology, 8th Edition by H. P. Rang, J. M. Ritter, R. J.
Flower, G. Henderson; Elsevier Churchill Livingstone; Pg no. 530-535
3) Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th Edition
by Laurence L. Brunton and Bjorn C. Knollmann; Pg no.489-504
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29. T H A N K
Y O U
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Any questions