Local anesthetics work by blocking sodium channels, preventing the transmission of electrical signals in nerves. They are commonly used for minor surgical procedures and can be administered via different routes. The most commonly used local anesthetics are amide and ester derivatives that exist in both ionized and non-ionized forms, with the non-ionized forms able to more readily cross cell membranes and the ionized forms being the active blocking entities inside axons. Toxicity can occur if local anesthetic blood levels become too high, potentially causing CNS or cardiovascular effects like seizures or arrhythmias. Treatment of local anesthetic toxicity focuses on supportive measures.

1. LOCAL ANESTHESIA

2. DEFINATION
Definition:
“Local anesthetics constitute a group of Chemically similar
agents(esters and amides) that block the sodium channels of excitable
membranes”
Routes of administration:
1. Intravenously
2. Tropical
Objective:
Sensory transmission from a local area of body to the CNS is blocked.

3. Classification of Local anesthetics

4. Chemistry of
local
anesthetics

5. Chemistry of Local anesthetics
● Most local Anesthetic drugs are esters or amides
of simple benzene derivatives.
● Subgroups within the local anesthetics are based
on this chemical characteristic and on duration of
action.
● The commonly used local anesthetics are Weak
bases with at least one ionizable amine function
that can become charged through the gain of a
proton.
● The pH of tissue may differ from the physiologic
pH so the degree of ionization of the drug may
vary.

6. Pharmacokinetics

7. ABSORPTION
Many short acting local anesthetics are readily
absorbed into blood from the injection site after
administration. The duration of local action is
therefore limited unless blood flow to the area is
reduced. This can be accomplished by
administration of a vasoconstrictor with the local
anesthetic agent.
Exception:
● Cocaine has an intrinsic sympathomimetic
action.
● The longer acting agents are also less
dependents on the coadministration of the
vasoconstrictor.

8. Metabolism:
● Biotransformation of amides occurs
primarily in the lever in part by
cytochrome p450 isozymes.
● Esters are bio transformed by the
plasma cholinesterase. Patients with
pseudocholinesterase deficiency may
metabolize ester local anesthetics
more slowly. Metabolism is very rapid
for procaine, slower for cocaine, and
very slow for tetracaine.

9. Eliminations:
● Liver dysfunction may increase the
elimination half life a amide local
anesthetics.
● Acidification of urine promotes
ionization of local anesthetics. The
charged forms of such drugs are more
rapidly excreted than non-ionized
forms.

10. Mechanism of Action

11. Local anesthetics block voltage-gated
sodium channels and reduce the influx of
sodium ions, thereby preventing
depolarization of the membrane and
blocking conduction of action potential.

13. Local Anesthesia Entry Inside Sodium Channel
● Drug molecule should be lipophilic to cross the lipid membrane to
reach the cytoplasm.
● The more lipid soluble (non-ionized and uncharged) form reaches
effective intracellular concentrations more rapidly than does the
ionized form.
● Inside the axon, the ionized (charged) form of the drug is the most
effective blocking entity.
Conclusion: Both ionized and non-ionized forms of the drug play important
roles:
○ The first in reaching the receptor site
○ The second in causing the effect

16. Pharmacological
effects

17. Nerves:
● Smaller nerve fibers are
easily blocked compared to
larger fibers.
● Myelinated fibers are blocked
easily than unmyelinated.

18. Activated pain fiber:
● Fires rapidly thus pain sensation
appears to be blocked selectively by
local anesthetics.
● Fibers located in periphery of thick
bundle are blocked sooner than those
in the core.

19. Other tissues:
● Most local anesthetics also
have weak blocking effects
on skeletal muscle
neuromuscular transmission
but these actions have no
clinical application.

20. The mood elevation induced by cocaine
reflects action on dopamine or other
amide mediated synaptic transmission in
CNS rather than local anesthetic action.
Some of these local anesthetics confer
additional benefits such as anti-
arrhythmic effects of Lidocaine when
administered Intravenously.

21. Clinical Uses of Local
Anesthetics

22. 1. Minor surgical procedures
The local anesthetics are commonly used for minor surgical
procedures, often in combination with vasoconstrictors such as
epinephrine.
Onset of action may be accelerated by the addition of sodium
bicarbonate, which enhances intracellular excess of these weekly
basic compounds. Arti Caine has the fastest onset of action.

23. 2. Spinal anesthesia:
Local anesthetics are also used in spinal anesthesia and to produce
autonomic blockade in ischemic conditions. Slow epidural infusion at
low concentrations has been used successfully for postoperative
analgesia.
• Epidural injection
Repeated epidural injection in anesthetic doses may lead to
tachyphylaxis.

24. • Intravenous local anesthetics
Intravenous local anesthetics may be used for reducing pain In the
perioperative period.
• Order and parenteral local anesthetics:
oral and parenteral forms of local anesthetics are sometimes used in
neuropathic pain states.

25. Toxicity of Local
anesthetics

26. “Toxicity refers to how poisonous or harmful a
substance can be. ”
Causes of toxicity:
• Toxic blood level of drug
• Each drug has a weight base toxic
threshold.

27. Local anesthetics cause toxicity of different systems of body (CNS ,CVS etc.)
Effects of toxicity:
CNS effects:-
• Sedation
• Restlessness
• Nystagmus
• Tonic-colonic convulsions
• Coma + respiratory and cardiovascular depression

28. CVS effects:
1. Patients with preexisting cardiovascular disease may
develop: Heart block and other disturbances of Cardiac
electrical Functions.
2. Bupivacaine = arrhythmias and hypotension
3. Cocaine when used as drug of abuse = hypertension
with cerebral damage , Cardiac arrhythmias and
myocardial infarction.

29. Other toxic effects:
• Allergic reactions
• Metabolized product of Prilocaine Converts hemoglobin
into methemoglobin ,causes decompensation In patient
of Cardiac and pulmonary disease.
• May cause local neurotoxic action that includes
histologic damage and permanent impairment of
function.

30. Treatment of toxicity

31. • Severe toxicity is treated symptomatically, there is no antidotes
• Convulsions are managed with intravenous diazepam or short
acting barbiturate such as thiopental
• To control violent convulsive activity a neuromuscular blocking
drug may be used
• Hypoventilation with oxygen is also helpful
• But cardiovascular toxicity of bupivacaine overdose is difficult to
treat and cause fatalities in young adults

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