Local anesthetics work by reversibly blocking sodium channels and inhibiting nerve impulse conduction. They are classified as esters or amides and include drugs like lidocaine, bupivacaine, and procaine. Amides are metabolized in the liver while esters are metabolized by plasma cholinesterase. Adverse effects include CNS effects like dizziness and cardiovascular effects like hypotension resulting from high systemic levels. Local anesthetics provide benefits of conscious sedation during surgery but risks include potential systemic toxicity if inadvertently injected intravenously or an overdose is given.

1. Local anaesthetics
Dr Andre Mwana Ngoie
MD,Msc anesthesiology

2. cont
Chemistry of LA
Overview
Mechanism of action
Pharmacologic properties
Metabolism
Specific drugs and their therapeutic uses
Adverse effects and toxicity of local
anaesthetic

3. introduction
• A local anesthetic is a drug that causes
reversible local anesthesia and a loss of
nociception. When it is used on specific
nerve pathways (nerve block), effects such
as analgesia (loss of pain sensation) and
paralysis (loss of muscle power) can be
achieved.

5. Overview
• Local anesthetics produce a transient and
reversible loss of sensation (analgesia) in a
circumscribed region of the body without loss
of consciousness.
• Normally, the process is completely reversible.

6. Classification of LA
Local anaesthetics generally have a lipid-
soluble hydrophobic aromatic group and a
charged hydrophilic amide group.

7. Classification‘ cont
Amides include;
Lignocaine,
Bupivacaine
Mepivacaine
Etidocaine
Prilocaine.
.

8. Classification ‘cont
Esters include;
Cocaine
Procaine
Tetracaine
Chloroprocaine
Amethocaine

9. cont
• Local anesthetics are generally classified as
either esters or amides and are usually linked
to:
– a lipophilic aromatic group
– to a hydrophilic, ionizable tertiary (sometimes
secondary) amine.
• Most are weak bases with pKa ( 8 – 9), and at
physiologic pH they are primarily in the charged,
cationic form.

11. cont
• The potency of local anesthetics is positively
correlated with their lipid solubility, which may
vary 16-fold, and negatively correlated with their
molecular size.

12. cont
• These anesthetics are selected for use on the
basis of:
1. the duration of drug action
• Short: 20 min
• Intermediate: 1—1.5 hrs
• Long: 2—4 hrs
2. effectiveness at the administration site
3. potential for toxicity

13. Mechanism of action
Local anesthetics act by blocking sodium channels and
the conduction of action potentials along sensory nerves.
• Blockade is voltage dependent and time dependent.
• Most local anaesthetic agents are tertiary amine bases
that are administered as water-soluble hydrochlorides 9
B.HCI ).
• After injection , the tertiary amine base is liberated by the
relatively alkaline pH of tissue fluid.

14. a. At rest, the voltage-dependent sodium (Na+) channels
of sensory nerves are in the resting (closed) state.
• Following the action potential the Na+ channel
becomes active (open) and then converts to an
inactive (closed) state that is insensitive to
depolarization.
• Following repolarization of the plasma membrane
there is a slow reversion of channels from the inactive
to the resting state, which can again be activated by
depolarization.

16. cont
• During excitation the cationic charged form of local
anesthetics interacts preferentially with the inactivated
state of the Na+ channels on the inner aspect of the
sodium channel to block sodium current and increase
the threshold for excitation.

17. cont
b. This results in a dose-dependent decrease in impulse
conduction and in the rate of rise and amplitude of the
action potential.
• This is more pronounced in rapidly firing axons
• Local anesthetics gain access to the inner axonal
membrane by:
1. traversing sodium channels while they are more often in an
open configuration.
2. passage directly through the plasma membrane.

19. Pharmacologic properties
1. Administration and absorption
a. Local anesthetics, except cocaine, are poorly absorbed
from the GI tract.
• They are administered:
– topically, by infiltration into tissues to bathe local
nerves,
– by injection directly around nerves and their
branches
– by injection into epidural (on or outside the dura
mater) or subarachnoid spaces.

21. cont
a. The rate and extent of absorption to and from nerves
determines:
 the rate of onset of action
 termination of action
 the potential for systemic adverse effects.
• Absorption rate depends on:
 relative lipid solubility of the uncharged form
 the dose
 the drug's physicochemical properties
 tissue blood flow
 drug binding.

22. cont
i. Reduced pH, as in inflamed tissues, increases the
prevalence of the cationic form, which reduces
diffusion into nerves and thereby reduces local
anesthetic effectiveness.
ii. “Carbonation” of local anesthetic solutions
(saturation with carbon dioxide) can decrease
intracellular pH, which increases the prevalence
and activity of the cationic active form inside the
nerve.

23. c. All local anesthetics, except cocaine, are vasodilators
at therapeutic doses.
• Coadministration of a vasoconstrictor (e.g.,
epinephrine) with a local anesthetic (generally of short
or intermediate duration of action) reduces local blood
flow.
• This reduces systemic absorption of the local
anesthetic from the site of application, prolongs its
action, and reduces its potential for toxicity.

24. cont
• Epinephrine:
– should not be coadministered for nerve block in
areas such as fingers and toes that are supplied with
end-arteries because it may cause ischemia or
necrosis
– it should be used cautiously in patients in labor and in
patients with thyrotoxicosis or cardiovascular disease.

25. cont
2. Metabolism
a. Ester-type local anesthetics are metabolized by plasma
butyrylcholinesterase and thus have very short plasma
half-lives.
• The metabolic rate of these anesthetics is decreased in
patients with decreased or genetically atypical
cholinesterase.

26. cont
b. Amide-type local anesthetics are metabolized at
varying rates and to varying extents by hepatic
microsomal enzymes (dealkylation and conjugation).
• They are excreted in metabolized and uncharged form
by the kidney.
• The rate of metabolism of these anesthetics is
decreased:
 in patients with liver disease or
 decreased hepatic blood flow, or
 by drugs that interfere with cytochrome P-450 enzymes (e.g.,
cimetidine, alfentanil, midazolam).

27. Specific drugs and their therapeutic uses
1. Amides
a) Lidocaine, articaine
• Lidocaine is the prototype amide
• it has an intermediate duration of action.
• Lidocaine is generally preferred for:
– infiltration blocks
– epidural anesthesia.
• Articaine has a rapid onset of action with the same pKa
and toxicity as lidocaine.
the duration of drug action
1. Short: 20 min
2. Intermediate: 1—1.5 hr
3. Long: 2—4 hr

28. cont
b) Mepivacaine
• intermediate duration of action that is longer than
that of lidocaine.
• Actions:
– similar to those of lidocaine
– it causes less drowsiness and sedation.
• Mepivacaine is not used topically.

29. c) Prilocaine
 intermediate duration of action that is longer than
that of lidocaine.
 Actions:
– similar to those of lidocaine
– less toxic than lidocaine .
 Prilocaine should not be used in patients with
cardiac or respiratory disease or in those with
idiopathic or congenital methemoglobinemia
Prilocaine O-toluidine
Hgb
methemoglobin
methylene blue
Hgb

30. cont
d) Bupivacaine, Ropivacaine, Etidocaine
• These drugs have a long duration of action.
• Bupivacaine has greater cardiotoxicity than
other amide local anesthetics.
• Ropivacaine may have less cardiotoxicity than
bupivacaine.
• Etidocaine has a rapid onset of action.

31. cont
2. Esters
a) Procaine (prototype)
– Procaine is short-acting.
– Procaine is not effective topically.
b) Chloroprocaine
– Chloroprocaine is very rapidly metabolized by
plasma cholinesterase.
– Chloroprocaine has less toxic than procaine.

32. cont
c) Cocaine
– Cocaine is a short-acting
– used only for the topical anesthesia of mucous
membranes.
– Cocaine is a schedule II controlled substance that is
subject to abuse.

33. cont
d)Tetracaine
• Tetracaine is long acting but has a slow onset of action
(>10 min).
• Tetracaine is often preferred for:
– spinal anesthesia
– ophthalmologic use.

34. cont
e) Dibucaine
• Dibucaine is long acting but has a slow onset
of action (15 min).
• Dibucaine is used only for:
– topical
– spinal anesthesia.

35. cont
f) Benzocaine and butamben picrate.
– These anesthetics are used topically only to treat sunburn,
minor burns, and pruritus.
g) Proparacaine
• used topically for ophthalmology due to:
– rapid onset
– short duration.

36. cont
3. Other local anesthetics
a) Dyclonine
• has a rapid onset of action
• used topically.
b) Pramoxine
• used topically
• too irritating for the eye or nose.

37. Adverse effects and toxicity of local anesthetics
• Adverse effects are generally an extension of therapeutic
action to block the membrane sodium channel.
• They are usually the result of overdose or inadvertent
injection into the vascular system.
• Systemic effects are most likely to occur with
administration of the amide class.

38. cont
Adverse CNS effects
• include light-headedness, dizziness, restlessness,
tinnitus, tremor, and visual disturbances.
• Lidocaine and procaine may cause sedation and
sleep.
• At high blood concentrations, local anesthetics produce
nystagmus, shivering, tonic-clonic seizures, respiratory
depression, coma, and death.

39. cont
Adverse cardiovascular system effects:
• Develop at relatively higher plasma levels than do
adverse CNS effects.
• Bradycardia develops as a result of the block of cardiac
sodium channels and the depression of pacemaker activity.
• Hypotension develops from arteriolar dilation and decreased
cardiac contractility.

40. cont
Allergic reactions
• include rare rash, edema, and anaphylaxis.
– These reactions are usually associated with ester-
type drugs that are metabolized to derivatives of para-
aminobenzoic acid.

41. Types of fibers involved
Type A fibers (largest ) responsible for
conducting pressure and motor
sensations.
Type B fibers are myelinated and moderate
in size.
Type C fibers, transmit pain and
temperature sensations, are small and
unmyelinated.
LA block type C fibers more easily than
type A

42. SYSTEMIC TOXICITY
The magnitude depends on;
Dose injected
Vascularity of the injection site
Inclusion of a vasoconstrictor in the
local
anaesthetic solutions

43. CVS
Arteriolar dilatation
directmyocardial depression.
Bp
Bupivacaine>than lidocaine on
cardiovascular toxicity
Neurotoxicity: Are not neurotoxic except
chloroprocaine.

44. ADVANTAGES
1.The ability to have the patient conscious
during surgery.
2.A smooth recovery.
3.Postoperative analgesia.
4.Reduction in surgical stress.
5.Earlier discharge for out patients of day
patients.
6.Less expensive

45. ADV OF LA ‘CONT
5.Generalized toxicity may occur if the local
anaesthetic drug is given intravenously by
mistake, or an overdose is injected.
6.Some operations, e.g. thoracotomies, are
unsuitable for local anaesthesia.
7.There is a small but definite incidence of
prolonged nerve damage.

46. CLINICAL USES
Topical Anaesthesia
Local infiltration
Intravenous block
Peripheral nerve block
Epidural block
Subarachnoid block

47. Complications of LA
In high doses,LA can have toxic effects
caused by being absorbed through the
bloodstream into the rest of the body
(systemic toxicity).
This may significantly affect your breathing,
heartbeat, blood pressure, and other body
functions.
Adrenaline reduces the side effect;
1;100,000(2.2mls) or 1; 80,000(1.8mls)