LOCAL ANESTHETICS

(Drugs that eliminate pain locally)

Anesthetics:
Anesthetics are the agents which causes a loss of sensation with or without producing the loss of
consciousness.
Local Anesthetics:
Local anesthetics are the agents which when applied topically or parenterally to a localized area,
produce a condition of local anesthesia by reversibly blocking the nerve conductance that
transmit the feeling of pain from this locus (affected area) to brain.
Mechanism of action of local Anesthetics:
Local anesthetics bind to receptor near intracellular ends of Na-channels. This results in the
blockade of sodium current, resulting in:
1. Increase threshold for excitation
2. Slow impulse conduction
3. Decline of rate of rise of action potential
4. Decrease action potential amplitude
5. Blockade of ability to generate action potential
All these effects results in the loss of pain sensation as well as impairment of motor functions.
Characteristics for ideal local Anesthetics:
An ideal local anesthetic should possess following characteristics:
1. It should produce reversible blockade of sensory nerve fibers with minimal effect on the
motor fibers
2. It should have rapid onset of action and prolonged sufficient duration of action for the
completion of major surgical procedures without any systemic toxicities.
Classification of local Anesthetics:
Chemically local anesthetics are classified into two main classes:
I. Esters:
 Cocaine
 Procaine
 Tetracaine
 Benzocaine
II. Amides:
 Lidocaine
 Mepivacaine
 Ropivacaine
 Bupivacaine

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  Etidocaine
 Prilocaine
Pharmacological Actions of Local Anesthetics:
I. Effect on nerves:
 Local anesthetics preferentially block the small fibers because the distance over which
such fibers can previously propagate an electrical impulse is shorter. E.g, Type B
(preganglionic fibers) are blocked before Type C (dorsal,pain fibers and sympathetic post
ganglionic fibers).
 Myelinated nerves are blocked before unmyelinated nerves.
 In large nerve trunks ,motor nreves are blocked first because they are located
circumferentially.
 In extremities, proximal sensory fibers are blocked before the distal sensory fibers.
II. Effect on other excitable membranes:
 Local anesthetics have weak neuromuscular blocking effects
 They have antiarrhythmic activity.
Adverse effects of local Anesthetics:
I. CNS:
 Euphoria
 Sleepiness
 Headache
 Visual disturbance
 Auditory disturbance
 Restlessness
 Shivering
 Convulsions
 Depression
II. CVS:
 Hypotension
 CV collapse
III. Respiratory system:
 Respiratory depression
IV. Blood:
 Methemoglobinemia
V. Allergic reactions: are present
SAR of local anaesthetics:
1) Lipophilic portion of the molecule is essential for local anaesthetic activity.
2) In case of Amino esters (e.g., benzocaine, procaine) an electron donating substituent in
ortho- and para- or both positions increase local anaesthetic potency whereas in Meta
position only decrease the lipophilicity of molecule.

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 3) Electron withdrawing groups (such as –NO2, -C=O-, -C≡ N ) decreases local anaesthetics
activity.
4) Insertion of methylene group (-CH2-) between aromatic moiety and carbonyl function in
procaine, decrease the local anaesthetics activity.
5) Lengthening alkylene chain in lidocaine decreases the local anaesthetics activity.
6) In amides, the O, O-dimethyl group (e.g., in lidocaine) resist amide hydrolysis, thus,
increases the duration of action
7) Tertiary amine series (hydrophilic portion) is needed only for formation of water soluble
salts.
8) Local anaesthetics with higher lipid solubility and lower pKa values show more rapid
onset and lower toxicity.

Details of some local anesthetics:

I. Benzocaine: (synthesis)

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Clinical uses:
It is used for topical anesthesia.
Procaine hydrochloride:
Synthesis:
It can be prepared by two methods.But method 2 is more preferable.
(I)

( II )

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Clinical uses:
 Topical anesthesia
 Infilteration anesthesia
 Nerve block anesthesia
 Spinal anesthesia
I. Lidocaine or Xylocaine or Lignocaine Hydrochloride:
Synthesis:

Clinical uses:
It is used for
 Topical anesthesia
 Infiltration anesthesia
 Nerve block anesthesia
 Spinal anesthesia
 Arrhythmia

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