Local anesthetics work by blocking voltage-dependent sodium channels in nerves, preventing the conduction of action potentials. They are classified as esters or amides. Esters are metabolized rapidly via plasma esterases, while amides are metabolized more slowly, some via hepatic cytochrome P450 enzymes. Local anesthetics are used clinically for analgesia via various routes of administration depending on the specific agent. Toxicity can cause central nervous system effects like seizures as well as cardiovascular issues. Treatment focuses on supportive care and controlling symptoms.

1. Local Anesthetics
Dr.M.Usman Khalid
DPT,MS-NMPT

2. Local Anesthetics
 Local anesthesia is the condition that results
when sensory transmission from a local area of
the body to the CNS is blocked.

3. Classification
Esters:
Long action(tetracaine)
Short action(procaine)
Surface action(benzocaine,cocaine)
Amides:
Long action (bupivacaine,ropivacaine)
Medium action(lidocaine)

4. Pharmacokinetics
 Amides:
 Hepatic metabolism via CYP450 in part.
 Half-lives: lidocaine, prilocaine < 2 h, others 3–4 h.
 Esters:
 Rapid metabolism via plasma esterases
• short half-lives

5. Mechanism of Action
 Block voltage-dependent sodium channels.
 Reduce the influx of sodium ions, thereby preventing depolarization of
the membrane and blocking conduction of the action potential.
 The affinity of the receptor site within the sodium channel for the local
anesthetic is a function of the state of the channel, whether it is resting,
open, or inactivated.
 High concentrations of extracellular K+ may enhance local anesthetic
activity, whereas elevated extracellular Ca2+ may antagonize it.

6. Pharmacologic Effects
 Nerves:
 Smaller fibers are blocked more easily than larger fibers, and
myelinated fibers are blocked more easily than unmyelinated fibers.
 Activated pain fibers fire rapidly; thus, pain sensation appears to be
selectively blocked by local anesthetics.
 Fibers located in the periphery of a thick nerve bundle are blocked
sooner than those in the core.

7. Clinical Uses
Amides:
Analgesia via topical use, or injection (perineural,
epidural, subarachnoid)
 Rarely IV.
Esters:
Analgesia
 Topical only for cocaine and benzocaine.

8. Toxicity
 CNS Effects: light-headedness or sedation,
restlessness, nystagmus, and tonic-clonic
convulsions.
 Cardiovascular Effects:
 Vasodilators, heart block, cardiovascular toxicity,
including arrhythmias and hypotension.

9. Treatment of Toxicity
 Severe toxicity is treated symptomatically,there are
no antidotes.
 Convulsions are usually managed with intravenous
diazepam or a short-acting barbiturate such as
thiopental.
 Hyperventilation with oxygen is helpful.
 A neuromuscular blocking drug may be used to
control violent convulsive activity.