This document provides an overview of local anesthetics. It discusses their history, mechanisms of action, pharmacokinetics, clinical uses, and ideal characteristics. Local anesthetics work by reversibly blocking sodium channels in nerve cell membranes, inhibiting nerve impulse conduction. They are classified as esters or amides depending on their chemical structure. Factors like drug potency, onset of action, and duration are influenced by properties like lipid solubility and pKa. Local anesthetics have various clinical applications for procedures requiring temporary loss of sensation. The ideal local anesthetic would have characteristics like rapid onset and safe duration without side effects.

1. BRANCH OF
PHARMACOLOGY
LOCAL ANESTHETICS

2. OBJECTIVES FOR LOCAL ANESTHETICS
 General considerations and history
 Na +channels, cellular electrophysiology, & local anesthetic
actions
 Classify local anesthetics
 Mechanisms of action
 General characteristics of local anesthesia
 LA pharmacokinetics
 Pharmacological effects
 Clinic use
 LA toxicity
 Specific LA agents and actions
 Summary

3. WHAT ARE LOCAL ANESTHETICS?
 Local anesthetics are drugs applied topical or local
injection to produce a temporary loss of sensation
in a restricted area of body.
 Reversible loss of sensory perception by block
generation, and propagation oscillations of
electrical impulses [Prevent conduction of electrical
impulses from the periphery to the CNS], and also
in motor nerve and autonomic conduction without
a loss of consciousness.

4. WHAT ARE LOCAL ANESTHETICS?
 Unlike general anesthetics cause loss of feelings
without inducing unconsciousness.
 They normally do not cause central nervous system
(CNS) depression.
 General anesthetics act on the CNS or autonomic
nervous system to produce analgesia, amnesia, or
hypnosis.

5. HISTORY OF LOCAL ANESTHETICS
 Local anesthetics are derivatives of cocaine which is a
derivative of the coca leaf. The natives of Peru have
chewed the leaves of the indigenous plant “Erythroxylon
coca” the source of cocaine, to induce a feeling of well-
being
 Koller used cocaine for the eye in 1884
 1884 William S. Halsted used cocaine as nerve block
 Einhorn First synthetic local—procaine (Novocaine) in
1904
 Lofgren synthesized Lidocaine in 1943

6. HISTORY OF LOCAL ANESTHETICS
 Procaine was prepared in 1943.
 In 1957, Boaf Ekenstam et al. synthesized mepivacaine
and bupivacaine
 in 1969, prilocaine was synthesized by Nils Löfgren and
Cläes Tegner ; and
 in 1972, Adams et al. developed etidocaine
 Currently, the pharmaceutical industry continues to
explore the development of safer and more effective
local anesthetics in a pursuit that has come a long way
since the earliest experiments with cocaine

7. LOCAL ANESTHETICS SEQUENCE OF EVENTS WHICH
RESULT IN CONDUCTION BLOCKADE
 LAs are weak bases (pKb7–8).
 They exist as an equilibrium between ionized (LAH+)
and unionized (LA) forms.
 The unionized forms are lipid soluble and cross the
axonal membranes into the axoplasm.
Intracellularly, after that the part of the unionized
forms protonates into the ionized [cationic] forms.
 The ionized [cationic] forms bind to the intracellular
end receptors, obstruct, and block Na+ channel.

8. LOCAL ANESTHETICS SEQUENCE OF EVENTS WHICH
RESULT IN CONDUCTION BLOCKADE
 Inhibiting the Na permeability into the nerve
cytoplasm, thus inhibiting the flow of K out of the
cell that underlies action potential.
 Failure to achieve the threshold potential
 Decrease in the rate and degree of the
depolarization phase of the action potential
 Lack of development of a propagated action
potential [Blockade of impulse conduction]

9. LOCAL ANESTHETICS SEQUENCE OF EVENTS WHICH
RESULT IN CONDUCTION BLOCKADE
 This blocking is nonselective, which means that both
sensory and motor impulses are affected.
 Its action is use-dependence. Reasons:
Anaesthetic molecules gain access to the channel
more readily when the channels is open.
Anaesthetic molecules have higher affinity for
inactivated than for resting channels.
 Increase in extracellular Ca+ partially antagonizes the
action of LA, this is probably because LA compete with
Ca ions for a site in the nerve membrane that controls
the passage of Na+ through these channels.

10. STRUCTURAL CHARACTERISTICS OF
NA CHANNELS
 Large α subunit
Homotetramer and
1 or 2 smaller β subunits

11. ONSET MODE OF ACTION

12. PHARMACOLOGIC EFFECTS OF
LOCAL ANESTHETICS
 The main pharmacologic effect of the local
anesthetic is to reversibly block peripheral nerve
conduction.
First, autonomic activity is lost [Sympathetic block
(vasodilatation)]
Then pain, temperature sensation and other
sensory functions [proprioception (touch and
pressure sensation)] are lost.
Last, motor activity is lost.

13. PHARMACOLOGIC EFFECTS OF
LOCAL ANESTHETICS
 As local drugs wear off, recovery occurs in reverse
order (motor, sensory, then autonomic activity are
restored)
 Direct relaxation of smooth muscle & inhibition of
neuro-muscular transmission in skeletal muscle
producing vasodilatation.
Intra-arterial procaine reverse arteriospasm
during I.V. Sedation

14. PHARMACOLOGIC EFFECTS OF
LOCAL ANESTHETICS
 Class I antidysrhythmic-like action on the heart:
Local anesthetics also have a direct effect on the
cardiac muscle by blocking cardiac Na channels
and depressing abnormal cardiac pacemaker
activity, excitability, and conduction.
 Stimulation and/or depression of the CNS.

15. LOCAL ANESTHETICS BIND AND INHIBIT MANY
DIFFERING CHANNELS, AND RECEPTORS
 Na, K, Ca channels
 G-protein modulation of channels or with many
enzymes
Adenylyl cyclase
Guanylyl cyclase
Lipases
 Many receptors
Nicotinic acetylcholine
NMDA

16. MANY CLASSES OF COMPOUNDS
BIND AND INHIBIT SODIUM CHANNELS
 Prolongation of local anesthetics action
General anesthetics [Halothane]
Ca channel blockers [Dihydropyridine]
Alpha2 agonists [Clonidine]
Tricyclic antidipressants
Substance P antagonists [Opioids]
Many nerve toxins[Batrachotoxin – Grayanotoxin–
Veratridine- Tetrodotoxin(TTX) -Saxitoxin]

17. CHEMICAL STRUCTURE
AND CLASSIFICATION
 All local anesthetics [ LA ] contain an aromatic ring
[Benzene ring ] at one end of the molecule and an
amine [tertiary amine functional group at the
other, separated by intermediate bond either an
ester or amide group linking them
 LAs segregate into esters and amides, based on the
chemical link between them.

19. LOCAL ANESTHETICS

23. PHYSIOCHEMICAL PROPERTIES
 Therefore, all local anesthetics are classified as
esters or amides.
 This is important because the amides are chemically
stable in vivo, Metabolized by mixed function
oxidases (CYP450) longer half-lives
 Whereas the esters are more rapidly subject to
hydrolysis by blood and tissue estrases short half-
lives. In addition, the hydrolysis of an ester local
anesthetic leads to the formation of para-
aminobenzoic acid (PABA), which causes an allergic
response in some individuals.

25. A DIFFERENTIAL SENSITIVITY OF NERVE
FIBERS TO LOCAL ANESTHETICS
The fibers in the nerve trunks are affected according to:
1- Fiber diameter:
 Type B (preganglionic autonomic) then type C
(dorsal root for pain) and then Smaller fibers [un-
myelinated fibers] [Aδ fibers (pain and temperature)
more LA-sensitive than Aβ fiber (touch and pressure) and
then Aα fibers (proprioception, motor)].The time of onset
of action is shorter for the smaller fibers and the
concentration of the drug required is also less.

26. A DIFFERENTIAL SENSITIVITY OF NERVE
FIBERS TO LOCAL ANESTHETICS
2- Myelination:
 All LAs will block myelinated before unmyelinated
fibers of smaller diameter at lower concentration
than are required to block larger fibers of the same
type for this reason pre-ganglionic B fibers may be
blocked before the unmyelinated C fibers involved
in pain transmission. For myelinated fibers at least
two successive nodes must be blocked by The LA to
halt impulse propagation.

27. A DIFFERENTIAL SENSITIVITY OF NERVE
FIBERS TO LOCAL ANESTHETICS
3- Firing frequency (conduction velocity):
 LA effect is more marked on fibers of higher
frequencies of depolarization and longer periods of
depolarization especially pain fibers. Motor fibers
fire at a slower rate and have shorter action
potential duration.
4- Fiber position:
 The location of the fiber in the peripheral nerve
bundle whether sensory or motor is important.
Fibers located circumferentially are blocked first
because they are the first to be exposed to the
drug therefore it is not uncommon that motor
nerves are blocked before the sensory in large

28. A DIFFERENTIAL SENSITIVITY OF NERVE
FIBERS TO LOCAL ANESTHETICS
 Smaller nerve fibers have a proportionally smaller
critical length.
 Bupivacaine and ropivacaine are relatively selective for
sensory fibers ; adequate sensory analgesia , with little
or no motor block.
 By increasing concentration: The general order of
loss of function is as follows
Pain fibers
Sensory fibers [temperature-touch-proprioception]
Motor fibers [skeletal muscle tone]

29. PHARMACOKINETICS OF
LOCAL ANESTHETICS
 Absorption: Systemic absorption of injected local
anesthetic from the site of administration is
modified by several factors, including:
Dosage
Site of injection
Drug-tissue binding
The presence of vasoconstricting substances
The physiochemical properities of the drug.

30. PHARMACOKINETICS OF
LOCAL ANESTHETICS
 Peak LA concentrations vary by the site of
injection.
After plexus, epidural, or intercostal blocks, the
latter consistenly produced the greatest peak LA
concentrations.
 Distribution: be related with tissue perfusion,
liposolubility, and pH.
The least potent, shortest-acting LAs are less
protein-bound than the more potent, longer-
persisting agents.

31. PHARMACOKINETICS OF
LOCAL ANESTHETICS
 Metabolism (Biotransformation)
Ester Local Anesthetics: hydrolyzed in the plasma by
the enzyme pseudocholinesterase. Metabolic
products is para-aminobenzoic acid (PABA)
allergen. Ester metabolism can, theoretically, be
slowed by cholinesterase deficiency or long-term
cholineserase inhibition.
Amide Local Anesthetics: primary site of metabolism
of amide local anesthetics is microsomal enz. in the
liver. Amide clearance is highly dependent on hepatic
blood flow, hepatic extraction and enz. function.
Used with care in patients had severe liver disease.

32. PHARMACOKINETICS OF
LOCAL ANESTHETICS
 Excretion: [in urine 2-5% of active drug form] first-
order kinetics, t ½ is constant.

33. EFFECTS OF MEDICAL CONDITIONS &
DRUGS ON LA DOSING & KINETICS
 Renal failure: ↑Vd; ↑accumulation of metabolic
products
 Hepatic failure: ↑amide Vd, ↓amide clearance
 Cardiac failure: β and H2 blockers: ↓hepatic blood
flow and ↓amide clearance
 Cholinesterase deficiency or inhibition: ↓ester
clearance
 Pregnancy: ↑hepatic blood flow; ↑amide
clearance; ↓protein binding

34. LA PHARMACODYNAMICS
Potency, duration of action , speed of onset, and
tendency for differential block.
 LA potency
The larger, more lipophilic LAs permeate nerve
membranes more readily and bind Na channels
with greater affinity.
Potency = lipid solubility [Higher solubility = can
use a lower concentration and reduce potential
for toxicity]

35. LA PHARMACODYNAMICS
 LA Duration : regulated by protein binding
It is a misconception that the duration of regional
anesthesia directly relates to LA protein binding.
More lipid soluble LAs are less relatively water -
insoluble and, therefore, highly protein - bound. It
is more logical to state that LA duration of action
relates to LA lipid solubility.

36. LA PHARMACODYNAMICS
 Local anesthetic should be used generally depends
on the duration of action of the procedure.
For short procedures, procaine would be
recommended [2-chloroprocaine]
An intermediate duration of action is found with
cocaine, lidocaine, and mepivacaine.
Long-acting local anesthetics include (bupivacaine
and levobupivacaine), ropivacaine, tetracaine, and
etidocaine.

37. LA PHARMACODYNAMICS
LA Speed of Onset : Controlled by pKa
 At any pH , percentage of LA molecule present in the
uncharged form is largely responsible for membrane
permeability decrease with increasing pKa.
 LAs are weak bases more potently block action
potential at basic pH , where there are increase amount
of LA in the uncharged form, than at more acid pH.
 Generally faster onset of clinical anesthesia when
bicarbonate added (esp. LA + Epi)

38. LA PHARMACODYNAMICS
LA Speed of Onset : Controlled by pKa
 Once injected into local tissue. If there is an
infection or inflammation, the free base form
decreases and less drug penetrates the tissue.
 One should consider the two LAs of fastest onset in
the clinic : eticocaine and chloroprocaine.

39. LA PHARMACODYNAMICS
Other Factor Influencing LA Activity.
 A variety of factor influence the quality of regional
anesthesia, including LA dose, site of
administration, additives , temp. , and pregnancy.
 Site of administration: In general , the fastest onset
and shortest duration of anesthesia occurs with
spinal or subcutaneous injections ; a slower onset
and longer duration are obtain with plexus blocks.

40. LA PHARMACODYNAMICS
Other Factor Influencing LA Activity.
 Additives
 Epinephrine is frequently added to LA solution in a
:100,000 dilution.
 Other popular LA additives include clonidine,
opioids, neostigmine, hyaluronidase, and that the
addition of [NaHCO3] sodium bicarbonate to Las
speeds the onset of nerve blocks.

41. LA PHARMACODYNAMICS
Other Factor Influencing LA Activity.
 Temperature
 The potency of LAs increase in vitro and in vivo with
cooling in some circumstances, but not in others.
 Pregnancy
 Spread of epidural or spinal anesthesia increase
during pregnancy. Pregnancy appears to increase
the susceptibility of nerves to LAs.

43. THE CHARACTERISTICS OF THE IDEAL
LOCAL ANAESTHETIC
1. Sterilization by autoclave: sterilize a local anesthetic solution
by autoclave.
2. Water soluble & Stability in solution
3. Potent
4. Adequate tissue penetration
5. Rapid onset and satisfactory duration: one desires a local
anesthetic with a relatively rapid onset of action.
6. Reversible & selective blockade of sensory nerves without
motor blockade.
7. Absence of local reactions: Local reactions such as irritation
are considered untoward and undesirable.
8. Absence of systemic reactions & allergic reactions
9. Low cost

44. CLINICAL USES
 Topical Surface Anesthesia (2–5%) (Application to
cornea, nasal or oral mucosa): nose, mouth, bronchial
tree (usually in spray form). Not effective for skin.
 Topical (usually ester): benzocaine, tetracaine, lidocaine,
prilocaine.

45. CLINICAL USES
 Infiltration anesthesia can produce with 0.25–0.5% (the
injection of local anesthetics under the skin) : direct
injection into tissues to reach nerve branches and
terminals).Used in minor surgery. Adrenaline often added
as vasoconstrictors (not with fingers or toes, for fear of
causing ischaemic tissue damage) through infiltration
(injection into the dermis and soft tissues located near
peripheral nerve endings). Infiltration: lidocaine,
procaine, bupivacaine, mepivacaine, prilocaine

46. CLINICAL USES
 Regional block Conduction anaesthesia: Local anaesthetics
is injected close to nerve trunks (e.g. branchial plexus,
intercostal or dental nerves), to produce a loss of
sensation peripherally. Used for surgery, dentistry.
Four types:
1. Nerve block: e.g. lidocaine, bupivacaine
2. Extradural(epidural): e.g. lidocaine, bupivacaine
a. Lumbar Epidural anaesthesia: LA injected into epidural
space, blocking spinal roots. Used for spinal anaesthesia,
also for painless childbirth. Epidural: bupivacaine.
b. Caudal space is sacral portion of epidural space. Needle
penetration of sacrococcygeal ligament from sacral hiatus.
Common regional technique in pediatric pts. Caudal:
lidocaine, bupivacaine

47. CLINICAL USES
3- Subarchnoid (intra thecal) or called spinal anesthesia: e.g.
tetracaine (preferred), lidocaine, mepivacaine.
Subarachnoidal anaesthesia (spinal anaesthesia):LA
injected into the subarachnoid space, to act on spinal roots
and spinal cord. Used for surgery to abdomen, pelvis or
leg. Main risks are respiratory depression and
hypotension. Spinal: bupivacaine, tetracaine
4- Intravenous: e.g. lidocaine, prilocaine.
Control of Cardiac Arrhythmias as lidocaine the primary
drug for treating cardiac arrhythmias. Minor operation
which need no loss of consciousness. In combination with
general anesthesia in order to decrease the dose of
general anesthetics. Relieve pain and itching.

49. ADVERSE REACTIONS LOCAL ANESTHETICS
Adverse reactions and toxicity of local anesthetics are
directly related to drug plasma levels. The factors that
influence toxicity include:
 Drug itself
 Concentration
 Route of administration
 Rate of injection
 Vascularity
 Patient’s weight

50. ADVERSE EFFECTS
 Local effects include
 Physical injury caused by poor injection technique: Pain,
Irritation, Ecchymosis, Hematoma and inflammation.
 Local hypoxia (if co-administered with vasoconstrictor).
 Longer acting local anesthetics (Bupivacaine) produce more
damage to skeletal muscle than do shorter acting agents.
 Tissue damage (sometimes necrosis) following
inappropriate administration (accidental intra-arterial
administration or spinal administration of an epidural
dose).
 Local neurotoxic actions that include histologic damage and
permanent impairment of function after spinal anesthesia
there might be prolonged sensory and motor deficit.

51. ADVERSE EFFECTS
 Central nervous system: Both CNS stimulation and
depression can occur.
More potent LA consistently produce seizure at
lower blood concentration and lower doses than
less potent LAs. Both elevated pCO and acidosis
decrease the LA convulsive dose.
At low doses, they include sleepiness, light-
headedness, visual and auditory disturbances.

52. ADVERSE EFFECTS
 Central nervous system: Both CNS stimulation and
depression can occur.
At higher concentration, restlessness, disorientation,
tremors, nystagmus and muscular twitching may
occur. Finally, overt tonic-clonic convulsions.
Treatment by drugs to control the seizures. (The
ultra–short-acting barbiturates and the
benzodiazepine derivatives, such as diazepam).
Continued exposure to high concentrations results in
general CNS depression; death occurs from
respiratory failure secondary to medullary
depression. Treatment requires ventilatory
assistance.

53. ADVERSE EFFECTS
 Respiratory and cardiovascular system:
local anesthetics have a direct relaxant action on
bronchial smooth muscle. Respiratory failure
secondary to CNS depression is a late stage of
intoxication.
Depress hypoxic drive
Apnea : central or peripheral

54. ADVERSE EFFECTS
 Respiratory and cardiovascular system:
CV Toxicity [Occur when blood concentration is at
least 3 times that producing seizure].
Cardiac toxicity is generally the result of drug-
induced depression of cardiac conduction [Negative
chronotropic effect] (AV block, intraventricular
conduction block) and these effects may progress to
severe hypotension and cardiac arrest.
Hypotension is a late effect that can occur as the
result of myocardial depression [Negative ionotropic
effect]. Peripheral arterial vasodilation and
autonomic nerves except with cocaine.

55. ADVERSE EFFECTS
There are reports of simultaneous CNS and CV
toxicity with bupivacaine and related agents.
The bupivacaine R[+] isomer binds cardiac Na
channels more avidly than the S [-] isomer ,
forming the basis for the development of
ropivacaine and levo-bupivacaine.
Bupivacaine can cause serious arrhythmias) or the
CNS (tetracaine can cause convulsions and eye
disturbances; cocaine – euphoria, hallucinations,
and drug abuse).

56. ADVERSE EFFECTS
 Complictions of spinal anesthesia :
 Hypot. or spinal shock
 Headache due to CSF leakage
 Septic meningitis
 Respiratory paralysis
 Allergic reactions:
 Uncommon. Include allergic dermatitis, urticaria,
hypotension, tachycardia and arrhythmia.
 True anaphylaxis has been documented with esters
(procaine, tetracaine, benzocaine) particularly those which
are metabolized directly to PABA [para-aminobenzoic acid]
which is a competitive antagonist of the sulfonamides.
 Anaphylaxis to amide anesthetic is much less common.

57. ADVERSE EFFECTS
 Some systemic unwanted effects due to the
vasoconstrictors - NA or adrenaline. They include
hypertension and tachycardia.
 Malignant hyperthermia only occurs in those persons
with the inherited autosomal dominant gene. It is not
related to amide local anesthetic use.
 Prilocaine and benzocaine may cause
methemoglobinemia, oxidation of ferric form of
hemoglobin to ferrous form. Visible cyanosis results
when concentration exceeds 1.5 g/dL. Usually benign.
 Mepivacaine is not used in obstetrics due to increased
toxicity in neonates

58. TREATMENT OF LA TOXICITY
 Essential treatment of LA-induced seizure should
include maintaining the airway and providing
oxygen. Seizures may be terminated with IV
thiopental , BZP, or a paralytic dose of succinyl
choline followed by tracheal intubation.
 Hypotension may be treated by IV fluid and
vasopressors.

59. ESTER LOCAL ANESTHETICS
Amino-esters (“Esters”)
 Older class of drugs. Derivatives of PABA (p-
aminobenzoic acid). Hydrolyzed by serum
cholinesterase.
 Commonly used local anesthetics containing the
ester functional group are Cocaine, Benzocaine,
Procaine, 2-chloroprocaine, Tropocaine, Eucaine,
(Novocaine), Tetracaine, and Amethocaine.

60. COCAINE
 1860 - cocaine isolated from erythroxylum coca
 Koller & Gartner - 1884 uses cocaine for topical
anesthesia
 Halsted - 1885 performs peripheral nerve block with local
cocaine directly into mandibular nerve and brachial
plexus
 Bier - 1899 first spinal anesthetic

61. COCAINE
 Blocking reuptake of cathecholamines in the presynaptic
neurons: Norepinephrine Dopamine and Serotonin
 Cholinergic stimulation
 Blocking sodium channels : Local anesthetic, Class I
antiarrhythmic

62. PHARMACOLOGICAL EFFECTS OF
COCAINE
EFFECTS OF COCAINE ON HEMODYNAMICS
 HR, BP, myocardial contractility, cardiac
output, Cardiac function (Direct myocardial
toxicity).
 CVS effects: It causes vasoconstriction, hypertension
emergency/Pulmonary edema, tachycardia,
Arrhythmias and Myocardial ischemia and infarction
because cocaine blocks the uptake of
catecholamines at the adrenergic terminal.

63. COCAINE
 Cocaine is 2 times as potent as procaine.
 Cocaine: useful in topical use because of the
vasoconstriction [Cocaine prevents the uptake of
catecholamines (adrenaline, noradrenaline) into
sympathetic nerve endings], thus increasing their
concentration at receptor sites, so that cocaine has a
built-in vasoconstrictor action. Which is why it retains a
(declining) place as a surface anesthetic for surgery
involving mucous membranes. It is used for ear, nose and
throat procedures.

64. COCAINE
 Cocaine has a rapid onset of action (1 minute), Half-life
30 minutes. and duration of up to 2 hours, depending on
the dose.
 The CNS is stimulated, The euphoria and cortical
stimulation it produces is responsible for the drug’s
abuse.
 Over dosage leads to convulsions followed by CNS
depression.
 Tolerance, abuse, anorexia and hyperpyrexia.
 Toxicity prohibits its use for other than topical anesthesia.

65. BENZOCAINE
 Benzocaine (Solarcaine, Orajel, Lanacaine etc)
 Topical use only, due to its poor water solubility, and
because of its low toxicity, it is used in concentration up
to 20%. It is used for minor mouth conditions (i.e
teething, canker sores) sore throat, sunburn, and other
minor skin conditions.
 Hydrolyzed rapidly by plasma esterase to p-aminobenzoic
acid [PABA] accounting for its low toxicity.
 Rapid sensitization-Avoid

66. PROCAINE (NOVOCAIN)
 1904 Einhorn discovers procaine (Novocaine)
 First synthetic LA
 Procaine is the prototype drug of the local anesthetics.It has
the lowest potency (except for Benzocaine). It’s an ester of
diethyl amino ethanol.
Pharmacokinetics:
 It is well absorbed following parenteral administration.
 Slow onset. It has short duration of action (30-45min). Very
short half-life.
 Metabolism: Rapidly metabolized by plasma pseudo-
cholinesterase. The metabolic product of procaine hydrolysis
is PABA, which inhibits the action of sulfonamides.

67. PROCAINE
Therapeutic uses:
 It can be used in all kinds of anesthesia except surface
anaesthesia.
 It is used for nerve block, epidural and spinal anesthesia.
Novocaine is generally not used in dentistry anymore.
 It has an excellent vasodilatory properties. Used intra-
arterially, as part of the recognized regimen, to treat the
arteriospasm which might occur during intravenous
sedation.

68. PROCAINE
 Adverse effects:
 CNS-restlessness, shivering, anxiety, occasionally
convulsions followed by respiratory depression.
 CVS-bradycardia and decreased cardiac output,
vasodilation.
 Allergic reactions.

69. 2-CHLOROPROCAINE
 Ester local anesthetic. Best suited for short procedures
 Initially associated with disconcerting neurotoxicity
(adhesive arachnoiditis) when administered in the
intrathecal space (inadvertently) Attributed to bisulfate
concentrations.
 Since the change in formulation no more reports of
neurotoxity.
 Large volumes of local anesthetic injected inadvertently
into the subarachnoid space may still cause neurotoxicity.

70. 2-CHLOROPROCAINE
 Other problem, back pain after large doses of > 25 ml of
local anesthetic
 Formulations contained EDTA, thought that it “leached”
calcium out of the muscle and resulted in hypocalcemia.
 Available in concentrations of 2% (for procedures that do
not require absolute muscle relaxation) and 3% which
provides for dense muscle relaxation.
 2-chloroprocaine will interfere with the action of
epidurally administered opioids

71. 2-CHLOROPROCAINE

72. TETRACAINE (PONTOCAINE)
Pharmacokinetics:
 It is approximately 10 times more potent (more toxic) than
procaine.
 Its onset of action is approximately 1-3 min, and its duration
of action is between 2 and 3 h.
 Addition of epinephrine or phenylephrine (0.5 mg) will make
it last up to 5 hours for lower extremity surgical procedures
Pharmacokinetics:
 Epinephrine can increase the duration of blockade by up to
50%.
 Compared to bupivacaine, tetracaine produces a more
profound motor block

73. TETRACAINE
 Therapeutic uses:
 A 2% solution is used topically on mucous membranes.
Surface anesthesia of the eye, nose and throat.
 Tetracaine hydrochloride is a commonly used local
anesthetic for spinal anesthesia requiring 2 to 3 hours of
anesthesia and , in this context, usually is combined with
10% dextrose to increase the specific gravity so that the
solution is heavier than cerebrospinal fluid.

74. DIBUCAINE
 Dibucaine is long acting but has a slow onset of action (15
min).
 Dibucaine is used only for: topical spinal anesthesia.

75. AMIDE LOCAL ANESTHETICS
Amino-amines (“Amines”)
 Newer class of drugs. Derivatives of aniline. Hepatic
degradation
 Commonly used local anesthetics containing the amide
functional group are Lidocaine, Bupivacaine (Marcaine,
Sensoricaine, Polocaine), Cinchocaine, Mepivacaine
(Carbocaine), Prilocaine, Ropivacaine, and Etidocaine

76. LIDOCAINE (LIGNOCAINE; XYLOCAINE)
 In 1943 Lofgren discovers lidocaine (Xylocaine)
 Prototypical amide local anesthetic.
 1.5-2% concentrations used for surgical anesthesia.

77. LIDOCAINE
Pharmacokinetics:
 It highly lipophilic, It is rapidly absorbed after parenteral
administration. Has half-life (t0.5) of 90 minutes.
 It is metabolized in the liver by microsomal mixed-
function oxidases and its metabolites are less toxic with
no action.
Pharmacokinetics:
 Epinephrine will prolong the duration of action by 50%
 Addition of fentanyl will accelerate the onset of analgesia
and create a more potent/complete block

78. LIDOCAINE
 Pharmacologic effects:
 Rapid onset of anesthesia.
 Its duration of action is 1.5 h.
 A greater potency and longer duration of action than
procaine in the area of dental anesthesia.
 Minimal local irritation.
 Moderate topical activity.

79. LIDOCAINE
Therapeutic uses:
 It be used widely for local anesthetic, and intravenously,
as an antiarrhythmic agent from class IB [Decreases the
duration of AP], used for the treatment of ventricular
tachyarrhythmia from myocardial infarction, ventricular
tachycardia, and ventricular fibrillation.
 Used topically for minor dermatological procedures (i.e
skin tag removal)
 ADRs: Bradycardia, AV block, (-) inotropic effect,
disturbances of GIT, rashes
 As procaine, but less tendency to cause CNS effects.

80. LIDOCAINE

81. PRILOCAINE
 Similar to lidocaine.
 A very potent local anaesthetic and is less toxic than
Lignocaine / Low CV toxicity profile.
 It produces less vasodilatation than lignocaine
 Rate of clearance is higher than other amide-types,
suggesting extra-hepatic metabolism with relatively low
blood concentration. It’s metabolite o-toluidine lead to
methaemoglobinaemia (more than 600 mg in adults)
after large IV bolus.
 Crystals of prilocaine and lignocaine base, when mixed,
dissolve in one another to form a eutetic emulsion that
penetrates skin in EMLA cream for premedication
venepuncture in children.

82. MEPIVACAINE (CARBOCAINE)
 Similar to lidocaine. Amide local anesthetic used in similar
concentrations.
 Onset & duration: Rapid onset but slightly shorter duration.
 Lasts about 15-30 minutes longer than lidocaine.
 Metabolized in the liver and has t0.5 of 120 minutes.
 Possess the least vasodilating effect.
 Epinephrine will prolong the duration of action by 50%.
 It’s main indication is when local anaesthetic without
vasoconstrictor is needed. 3% plain is more effective than
lignocaine.
 This local anesthetic is used for dental procedures, surgical
procedures and during labor and delivery.

83. MEPIVACAINE

84. BUPIVACAINE
Pharmacokinetics:
 It is more potent and has a longer duration of action than
other LA, lasting for more than 24 h in some situations,
due grater binding capacity to plasma protein and
possibly as a result of increased tissue proteins binding.
 Bupivacaine has a high degree of protein binding and
lipid solubility which accumulate in the cardiac
conduction system and results in the advent of refractory
reentrant arrhythmias.
 Metabolized in the liver.

85. BUPIVACAINE
Therapeutic uses:
 It can be used in infiltration anaesthesia, conduction
anaesthesia, and epidural anaesthesia.
 0.125-.25% used for epidural analgesia
 0.5-0.75% concentrations used for surgical anesthesia
 Epinephrine will prolong duration of action but not to the
extent of lidocaine, mepivacaine, and 2-chloroprocaine.
Adverse effects:
 As lidocaine, Bupivacaine (as well as etidocaine) but greater
cardiotoxicity than the other long acting local anesthetics.
 (-)-Bupivacaine: S- (or L-) enantiomer Less toxic than (±)-
bupivacaine

86. BUPIVACAINE

87. LEVOBUPIVACAINE
 S isomer of bupivacaine
 Used in the same concentrations
 Clinically acts just like bupivacaine with the exception
that it is less cardiac toxic

88. ROPIVACAINE (NAROPIN)
 Mepivacaine analogue
 This is used for surgical procedures, including caesarian
sections. Although it is similar pharmacologically to
bupivacaine in onset, duration, and quality of anesthesia, it is
less cardiotoxic.
 Used in concentrations of 0.5-1% for surgical anesthetic
 Used in concentrations of 0.1-0.3% for analgesia [in doses for
analgesia there is excellent sensory blockade with low motor
blockade].
 Ropivacaine is unique among local anesthetics since it
exhibits a vasoconstrictive effect at clinically relevant doses.

89. ROPIVACAINE
Adverse effects
 a. Low concentration dosages: Dizziness-Sleepiness-
Restlessness
 b. Higher concentration dosages:Muscular twitching-
Seizures.
 Hypotension (except for cocaine, which can result in
vasoconstriction and hypertension, as well as cardiac
arrhythmias).

90. ROPIVACAINE

91. ETIDOCAINE
 Long acting amide local anesthetic, similar to Bupivacaine
but with faster onset.
 Metabolized in the liver.
 Not used clinically very often due to the profound motor
blockade it induces
 When used for surgical anesthesia it is used in a
concentration of 1%

92. LOCAL ANESTHETICS - SUMMARY
 LA bind and inhibit Na+ channels. Block dependent on
state of channel
 Tonic versus phasic block
 Potency increases with lipid solubility. Protein binding
not important
Pharmacokinetics
 Esters versus Amides
Toxicity
 Signs of CNS toxicity. CNS before CV toxicity
 Allergy

93. THANK YOU