2. STRUCTURE AND CHARACTERISTICS
• Weak bases
• Amphiphilic
• 3 structural parts
Hydrophilic site Secondary and tertiary amine
Linkage by Ester or amide bond
Hydrophobic site Aromatic region
4. Ester-linked LAs
• Shorter duration of action
• Less intense action
• Higher risk of hypersensitivity
Amide-linked LAs
• Longer duration of action
• More intense action
• Lower risk of
hypersensitivity reaction
8. MECHANISM OF ACTION
• Blocks the initiation and propagation of action
potential
• Prevents the voltage-dependent increase in
Na+ conductance
• Concn. dependent action
Unaltered
B, c and d shows effect on AP of increasing
conc. of LA
9. Na+
entry is prevented through the Na channels by
activation gate (m gate)
Threshold potential: opens the M gate and inflow of Na+
This depolarize the membrane
LA receptor is located within the receptor in the
intracellular half
LA crosses the axonal membrane in unionized lipophilic
form and re-ionizes
Re-ionized LA (BH) has affinity to the LA receptor
Upon binding to LA receptor, Na channel stabilizes in
inactive state (h gate)
Thus reduces the probability of channel opening and
blocking the impulse conduction
10. PHARMACOLOGICAL ACTIONS
• Nerve endings
• Nerve trunks
• Neuromuscular junctions
• Ganglionic synapses
• Non specific receptors
Local actions
• LA injected or locally applied get absorbed into the
systemic circulation and can produce systemic
effects
Systemic action
11. Local
actions
Ach
release from
motor nerve
endings
Paralysis of
skin and
voluntary
muscles
Myelinated
nerves
blocked
earlier
Small nerve
fibers are
more sensitive
Outer nerve
fiber in nerve
trunk are
blocked earlier
Proximal areas
supplied by
nerve are
affected
earlier
Pain
Temperatur
e
Touch
Deep
pressure
13. LA + Adr(1:50,000
to 1:200,000)
vasoconstriction
removal
Intensity
of block
Systemic
toxicity
Bloodless Sx
field
14. SYSTEMIC ACTIONS
CNS
Stimulation followed by depression
Mental confusion, restlessness,
convulsions
Cocaine is a powerful stimulant
Procaine and other synthetic LA have less
CNS toxicity
CVS
Cardiac depressant
Ventricular tachycardia
Vasodilation – fall in BP
17. PROCAINE
• Introduced in 1905, first synthetic LA
• Low potency, slow onset & short duration of action.
• Use: Infiltration anesthesia
• Toxicity fairly low
• Metabolized to paraminobenzoic acid inhibits the action of
sulfonamides
18. LIGNOCAINE OR LIDOCAINE
• Amide type
• Faster, More intense, Long lasting extensive anesthesia
• Toxicity seen with ing dose
• Clinically significant CV depression usually occurs at levels that produce
marked CNS effects.
• Metabolites contribute to some of these effects.
• Use – LA of intermediate duration, antiarrhythmic agent
20. BUPIVACAINE
• Potent, long acting with more sensory blockade than motor
• Preferred for prolonged analgesia during labor or post-op
period.
• With indwelling catheter – can be given for several days.
• More cardiotoxic than lignocaine
• Cardiotoxicity is difficult to treat & severity is enhanced in
the presence of acidosis, hypercarbia & hypoxemia.
21. ROPIVACAINE
• Slightly less potent than bupivacaine
• Lesser cardiotoxicity – S- enntiomer
has less toxicity.
• Slower uptake
• Suitable for both epidural and spinal
anesthesia.
• Even more motor sparing than
bupivacaine.
22. CHLOROPROCAINE
• Rapid onset, short duration of action
• Reduced acute toxicity – rapid metabolism
• Prolonged sensory and motor blockade after
intradural or spinal anesthesia.
• Toxicity due to preservatives
• Now prepared preservative free
23. PRILOCAINE
• Intermediate acting amide
• Similar to lidocaine
• Causes little vasodilatation – thus can be used without vasoconstrictor
• ed volume of distribution- CNS toxicity.
• Suitable for IV anesthesia
• Causes Methemoglobinemia – dose dependent usually above 8mg/kg
• Restricted use in obstetrics – neonatal methemoglobinemia
24. BENZOCAINE
• Poorly soluble therefore too slowly absorbed
to be toxic.
• Directly applied to wounds and ulcerated
surfaces – remain localized for long periods.
• Incorporated into a large no. of topical
preparations.
• Causes methemoglobinemia.
25. EUTECTIC MIXTURE OF LA (EMLA)
• Lidocaine and prilocaine (1:1 by weight)
• Melting point below room temperature
• Topical anesthetic for use on:
• Normal intact skin for local analgesia
• Genital mucous membranes for superficial minor surgery
• Pretreatment for infiltration anesthesia
26. TECHNIQUES OF LA USE
•Surface anaesthesia
•Regional anaesthesia
•Tumescent anaesthesia
•Infiltration anaesthesia
•Regional anaesthesia
•Intravenous regional anaesthesia
•Central Neuraxial block
•Subarachnoid block
•Epidural block
•Peripheral nerve block
27. ADVERSE EFFECTS
• Excessive absorption:
• Parathesia
• Anxiety
• Tremors & Convulsions
• Cardiovascular collapse – myocardial depression
• Respiratory failure
• Anaphylactoid reactions:
• Exclusively with ester type & extend to chemical gp
• Rare with amide, some are due to preservatives & most are due to co-administration of
epinephrine.
28. MANAGEMENT OF LA SYSTEMIC TOXICITY (LAST)
• Preparation:
Oxygen, standard monitoring, and IV access
Medications and resuscitation equipment
• Immediate management:
Stop LA injection and call for help
Manage ABC (airway, breathing and circulation)
• Intravenous lipid emulsion therapy
29. Intravenous lipid emulsion therapy:
• Shuttles any LA agent from high blood flow organs (heart or brain)
to storage or detoxification organs (muscles or liver)
• Improves the cardiac output and blood pressure
• Post-conditioning myocardial protection
Dose:
• Initial bolus: 100 mL over 2–3 min (1.5 mL kg
⋅ −1
if lean BW <70 kg)
• F/b: 20% infusion of 200–250 mL over 15–20 min (0.25
mL kg
⋅ −1
min
⋅ −1
if lean BW<70 kg)
• If circulatory stability is not attained, re-bolusing up to two further
times or increasing the infusion to 0.5 mL kg
⋅ −1
min
⋅ −1
• Maximum recommended dose: 12 mL kg
⋅ −1
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