Local anesthetics are drugs that cause reversible loss of sensation, especially pain, in a restricted area of the body when applied topically or injected locally. They block nerve impulse generation and conduction by stabilizing sodium channels in the inactive state. Common examples include lidocaine, bupivacaine, and procaine. Local anesthetics are used for surface anesthesia, infiltration anesthesia, nerve blocks, spinal anesthesia, and epidural anesthesia.

1. Dr. Subhash R. Yende
Asst. Professor,
Gurunanak College of Pharmacy, Nagpur

2.  Local anaesthetics (LAs) are drugs which upon topical application
or local injection cause reversible loss of sensory perception,
especially of pain, in a restricted area of the body.
 They block generation and conduction of nerve impulse at any part
of the neurone with which they come in contact, without causing any
structural damage.
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Dr. Subhash R. Yende

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5.  Weak bases with amphiphilic property
 A hydrophilic and a lipophilic are joined by an alkyl chain through an ester
or amide linkage
 Ester-linked LAs - Cocaine, Procaine, Chloroprocaine, Tetracaine,
Benzocaine
 Amide-linked LAs - Lidocaine, Bupivacaine, Dibucaine, Prilocaine,
Ropivacaine
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Dr. Subhash R. Yende

6. Features of amide LAs (compared to ester LAs)
• Produce more intense and longer lasting anaesthesia
• Bind to α1 acid glycoprotein in plasma
• Not hydrolysed by plasma esterases
• Rarely cause hypersensitivity reactions
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Dr. Subhash R. Yende

7.  The LAs block nerve conduction by
decreasing the entry of Na+ ions during
upstroke of action potential (AP)
 Bind with LA receptor, which is located
in the S6 segment of domain IV of
α subunit of Na+ channel
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Dr. Subhash R. Yende

8.  Binding of LA to its receptor stabilizes the channel in the inactivated
state and thus reduces the probability of channel opening
 Potency of a LA generally corresponds to the lipid solubility of its
base form (B)
 LA activity is pH dependent and use dependent
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Dr. Subhash R. Yende

9. Local action
 No/minimal local irritant action and block sensory nerve endings, nerve
trunks, neuromuscular junction, ganglionic synapse and receptors
 The sensitivity to LA is determined by diameter of the fibres as well as by
fibre type Small myelinated > non myelinated > large myelinated
 The LA often fails to afford adequate pain control in inflamed tissues
 Addition of a vasoconstrictor, e.g. adrenaline prolongs duration of action
of LAs
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Dr. Subhash R. Yende

10. Systemic action
CNS
 Stimulation followed by depression in a dose dependent manner
C.V.S.
 Heart -Cardiac depressants, but no significant effects are observed at
conventional doses. At high doses they decrease automaticity,
excitability, contractility, conductivity and prolong effective refractory
period (ERP).
 Blood vessels - LAs tend to produce fall in BP. This is primarily due to
sympathetic blockade, but high concentrations
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Dr. Subhash R. Yende

11.  Procaine is negligibly bound to plasma proteins, but amide LAs are bound
to plasma α1 acid glycoprotein.
 Ester-linked LAs (procaine) are rapidly hydrolysed by plasma
pseudocholinesterase and the remaining by esterases in the liver
 Amide-linked LAs (lidocaine) are degraded only in the liver microsomes
by dealkylation and hydrolysis.
 After oral ingestion both procaine and lidocaine have high first pass
metabolism in the liver
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Dr. Subhash R. Yende

12.  CNS effects – light headedness, dizziness, auditory and visual
disturbances, mental confusion, disorientation, shivering, twitchings,
involuntary movements, finally convulsions and respiratory arrest.
 Cardiovascular toxicity - bradycardia, hypotension, cardiac arrhythmias
and vascular collapse
 Hypersensitivity reactions like rashes, angioedema, dermatitis, contact
sensitization, asthma and rarely anaphylaxis occur
 Injection of LAs may be painful
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Dr. Subhash R. Yende

13. 1. Surface anaesthesia- topical application to mucous
membranes and abraded skin
2. Infiltration anaesthesia -infiltrated under the skin
in the area of operation—blocks sensory nerve endings
3. Conduction block -Injected around nerve trunks so that the area distal to
injection is anaesthetised and paralysed
a.) Field block - all nerves coming to a particular field are blocked Eg. herniorrhaphy,
appendicectomy, dentalprocedures, scalp stitching, operations on forearms and legs.
b) Nerve block - around the appropriate nerve trunks or plexuses Eg lingual, intercostal,
ulnar, sciatic, femoral, brachial plexus, trigeminal, facial, phrenic.
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Dr. Subhash R. Yende

14. 4. Spinal anaesthesia - injected in the subarachnoid
space between L2–3 or L3–4
Used for operations on the lower limbs, pelvis,
lower abdomen e.g. prostatectomy, fracture setting,
obstetric procedures, caesarean section, etc.
5. Epidural anaesthesia -The spinal dural space is
filled with semiliquid fat through which nerve roots
travel.
The LA injected in this space acts primarily on nerve roots (in the epidural as
well as subarachnoid spaces to which it diffuses) and small amount
permeates through intervertebral foramina to produce multiple paravertebral
blocks.
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16. KD Tripathi. Essentials of Medical Pharmacology, 8th edition, 2019,
Jaypee Brothers Medical Publishers (P) Ltd. New Delhi.
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