Everything you need to know about Local Anesthetics. Dose, mechanism of action, toxicity, management. How to use, where to use. It also contains receptors which are involved. Which factors prolongs and makes the drug work quicker.

1. LOCAL ANAESTHETICS
DR SAUD ABBAS
PG-III
ANAESTHESIA, KTH

2. CONTENTS
 CLASSIFICATION
 MECHANISM OF ACTION
 CLASSIFICATION OF NERVE FIBRE
 ONSET OF ACTION
 DURATION OF ACTION
 SYSTEMIC TOXICITY
 COMMONLY USED L.A
 SUMMARY

3. CLASSIFICATION
BASED ON CHEMICAL STRUCTURE:
ESTERS AMIDES
PROCAINE LIGNOCAINE
CHLOROPROCAINE MEPIVACAINE
TETRACAINE PRILOCAINE
BENZOCAINE BUPIVACAINE
COCAINE ROPIVACAINE
NOTE:
ESTERS ARE METABOLIZED BY
PSEUDOCHOLINESTERASE
(except cocaine which is metabolized in liver)
AMIDES re metabolism primarily in liver

4. MECHNISM OF ACTION
 Local anesthetics are deposited all around the nerve.
 Drug in undissociated (nonionized) form penetrates the axonal membrane.
 Once inside it gets dissociated (ionized).
 It is this dissociated(ionized, protonated, cationic or uncharged) form which binds to
sodium channel (alpha subunit) from inner side, blocking the channel, preventing
depolarization and action potential.
 Although local anesthetics can block sodium channel in any state however activated
channels (positive resting H+ {local anesthetic Axonal in undissociated form)
Membrane Na+ Local anesthetic in dissociated form blocks sodium channel from inside
very rapidly.

5. BASED ON DURATION OF ACTION
 SHORT DURATION (15-30 MIN)
1) Chloroprocaine: shortest acting local anesthetic
2) PROCAIEN
 INTERMEDAIATE (3O-90 MIN)
 Lignocaine
 Mepivacaine
 Prilocaine
 Cocaine

6. Based on Duration of Action
Long duration (2-3 hours):
 Bupivacaine.
 Levobupivacaine
 Ropivacaine.
 Tetracaine (Amethocaine).
 Etidocaine.
 Dibucaine: Longest acting local anesthetic

7. OTHER DRUGS WITH LOCAL
ANESTHETIC
PROPERTIES
 Opioids
anesthetics can be given pethidine in place of local anPethidine: Patients hypersensitive to
local
esthetics.
 Buprenorphine: Because of its local anesthetic properties it is frequently used to
supplement the effect of local anesthetics For nerve blocks.
 Tramadol: Although weak but tramadol do havelocal anesthetic properties.
 Methoxyflurane: The droplets o f methoxyflurane has got local anesthetic properties.

8. CLASSIFICATION OF NERVE FIBRE

9. ONSET OF ACTION AND FACTORS
EFFECTING IT.
 Depends on number of factors like:
 Dose and concentration: Higher dose or higher concentration facilitates onset
 pKa: It is the pH at which a local anesthetic is 50% ionized and 50% non ionized.
 Since local anesthetics are weak bases, agents with pKa closer to physiologic pH will
have more drugs in non ionized form which can diffuse through axonal membrane
enhancing the onset.
 That is why lignocaine with lower pKa of 7.8 has fast onset as compared to bupivacaine
with higher pKa of 8.l.

10. Continued
 Type of nerve fiber: A fibers are blocked earlier than B which are blocked earlier than C
 Frequency of nerve stimulation: Since activated channels are blocked more easily, a
stimulated nerve will be blocked earlier as compared to non stimulated nerve.

11. DURATION OF ACTION FACTORS
EFFECTING IT.
 It depends on:
1. Dose: Increased dose increases the duration.
2. Pharmacokinetic profile of drug: It includes:Potency (lipid solubility): Potency,
which correlates with lipid solubility, is directly proportional to duration; more the
potency, longer is the duration with the exception of chloroprocaine which in spite of
having intermediate potency is shortest acting.
3. Plasma protein binding (a l acid glycoprotein): Agents with high protein binding like
bupivacaine have prolonged action.

12. SYSTEMIC TOXICITY
CNS
 As central nervous system is the first system involved in local anesthetic toxicity.
 Typical sequence is excitation followed by depression of cerebral tissue (inhibitory
neurons are more sensitive than excitatory neurons). The common signs and symptoms
a numbness, dizziness, tongue paresthesia, visual and auditory disturbances,
twitching, tremors, convulsions followed by coma and death. Convulsions as first
presentation are quite common in local anesthetic toxicity.
 Treatment includes maintenance of adequate ventilation and oxygenation. Convulsion
can be controlled by diazepam/ midazolam or thiopentone.

13. Cardiovascular System
 Electrophysiological effects of local anesthetics on cardiac tissue are decrease in rate
of depolarization (main effect), effective refractory period and duration of action
potential
 All local anesthetics have negative inotropic action on myocardium, causes depression
of conduction system (prolonged PR interval and increased duration of QRS complex).
 At very high doses they may block conduction of sinus node producing bradycardia or
even sinus arrest. In addirion the above effects bupivacaine (and to lesser effect
levobupivacaine and ropivacaine) can also produce ventricular arrhythmias. Therefore,
either the isolated or combined actions like bradycardia, decreased myocardial
contractility, ventricular arrhythmias, hypotension can produce cardiac arrest with local
anesthetics. Management of cardiac arrest is immediate CPR.

14. Respiratory symptoms, Immunology,
 Lignocaine depresses hypoxic drive. Direct depression of medullary respiratory Centre
can occur at high dose
 Immunologic: Allergic reactions are common with esters but rare with amides. The
reaction with amides is because of the preservative (methyl paraben) it contains. Cross
sensitivity does not exist between classes (i.e. esters and amides) but exist between
agents of same class.

15.  Methemoglobinemia :
1. Usually seen with Prilocaine however benzocaine can also cause methemoglobinemia.
2. Treatment: IVmethylene blue.
 Coagulation: Lignocaine can inhibit coagulation

16. COMMONLY USED L.A
Lignocoine (Xylocoine, Lidocoine)
 Metabolism
Metabolized in liver, excreted by kidney.
t½: 1.6 hrs.
 Duration of Effect
Without adrenaline 45-60 minutes.
With adrenaline 2-3 hours.
 Maximum Safe Dose
Without adrenaline 4.5 mg/kg
(maximum 300 mg)
With adrenaline 7 mg/kg
( maximum 500 mg)

17.  Concentration used
1. Surface (topical) analgesia 4% and 10%
2. Nerve blocks 1-2%
3. Urethral procedures (as jelly) 2%
4. Spinal 5% (heavy)
5. Epidural 1-2%
6. Intravenous regional analgesia 0.5%
7. (Bier's block) Infiltration block 1-2%

18. BUPIVACAINE
 It is 4 times more potent than lignocaine.
 Metabolized in liver, t ½: 3.5 hours.
 MAXIMUM DOSE:
WITHOUT ADRENALINE: 2.5 MG/KG
(MAXIMUM DOSE 175MG)
WITH ADRENALINE 3 MG/KG
(MAXIMUM DOSE 225MG)
 DURATION OF EFFECT
WITHOUT ADRENALINE 2-3 hours.
WITH ADRENALINE 3-5 hours.
 Addition of adrenaline only prolongs the duration of sensory block.

19.  Concentration Used
1. For nerve block 0.5%
2. Spinal 0.5% (heavy)
3. Epidural 0.125-0.5% (depending whether used for sensory block or motor block)
 Cardiot0xicity of bupivacaine may manifest as bradyarrhythmias, conduction blocks,
ventricular arrhythmias or cardiac arrest. Its high tissue binding (slow reversal of
sodium channels} and high degree of protein binding makes resuscitation after cardiac
arrest prolonged and very difficult.
 Management of cardiac arrest
includes CPR along with the rapid bolus of lntralipid 20%, 1.5 mL/kg followed by
infusion if required. Intralipid binds the active form of bupivacaine

20. SUMMARY

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