Local Anesthetics

Moderator: Dr. Parminder

Presenter : Dr. Moneka
Agenda
• Definition
• History
• Classification
• Mechanism of action
• Nerve fibres classification
• Site of Administration
• Local Anesthetic Drug
• Clinical pharmacology
• Carbonate and pH Adjustment
• Toxicity
 Definition
• LA are drugs which block, generation and conduction of nerve impulse at all parts of
neuron where they come in contact
• Drugs upon topical application or local injection causes reversible loss of pain, in the
restricted region of body without causing permanent damage to tissue
• Applied to mixed nerves causes interruptions of sensory and motor impulse resulting
in loss of autonomic control and muscular paralysis
 History

• First LA, isolated from the leaves of eyrthroxylum coca- was cocaine- naturally
occurring alkaloids by Neiman.
• Anesthesia action was demonstrated by Karl Kollar in 1984 in ophthalmic surgery
• Dibucaine- 1st amide, produced by Mischer in 1929 and clinically used by Mc Elwain
in same year
• Various potent LA found in subsequent 2. AMIDES :
year:
• Mepivacaine -1956
1. ESTERS:
• Bupivacaine- 1951
• Tetracaine 1932
• Prilocaine- 1959
• Chloroprocaine -1955
• Etidocaine - 1971
Classification
Based on structure:

1. Amino amides:
• Eg: lidocaine, mepivacaine, prilocaine, etidocaine, ropivacaine
• Metabolised in the liver
• Stable solution
2. Amino esters:
• Eg: procaine, chlorprocaine, tetracaine, cocaine, benzocaine
• Hydrolysed by esterases ( except - cocaine - liver metabolism)
• High incidence of anaphylactic reaction due to structural similarity to PABA
Based on duration of action:
1. Short duration: low potency
• Procaine
• Chlorprocaine - shortest acting
2. Intermediate duration: intermediate potency
• Lidocaine
• Mepivacaine
• Prilocaine
• Cocaine
3. Long duration: High potency
• Bupivacaine
• Tetracaine
• Etidocaine
• Ropivacaine
• Dibucaine - longest acting
 Difference between Esters and Amides

ESTERS AMIDES

1. Combination of aromatic 1. Combination of organic

acid and alcohol acid and ammonia or amine

2. Detoxified in blood stream

by plasma 2. Detoxified in liver
pseudocholinesterase

3. Sensitivity reactions are

3. Less frequent
frequent

4. Stable and intense, long

4. Esters are unstable
lasting block
Mechanism of action
• All local anesthetics have an aromatic ring (lipophilic end ) and a tertiary amines
group (hydrophilic end ) connected by amide or ester bond.
• MOA: Block the conduction of impulses along the nerve fibres
1. Drugs injected convert into ionised and non ionised groups based on pH of
surrounding solution.

2. Dissociation of drug depends on pH of the media

 3. When local anaesthetic is injected into nerve
Drug converts into non- ionised form in extracellular pH(7.35)
This can penetrate cell membrane
In the cell, pH is slightly lower
Drug gets converted to ionised/ active form
Binds to sodium channels
Blocks conduction of impulses.
More hydrophobic compound - long acting
(More affinity to sodium channels )
Nerve fibres classification
• Nerve fibres classified into :
1. Myelinated

2. Unmyelinated
ERLANGER - GASSER CLASSIFICATION:
1. Vasomotor and sympathetic efferent

2. Temperature - cold

3. Warm

4. Slow pain

5. Fast pain

6. Cutaneous discrimination

7. Touch

8. Pressure

9. Motor fibres

10. Muscle, tendon joint sensation

11. Deep pressure

 Site of Administration
• SLOWEST ONSET:
After peripheral nerve block eg:brachial plexus block deposited away from the nerve
roots and longer time for diffusion to the nerves is required.
• RAPID ONSET :
After subarachnoid block deposition of LA in the vicinity of the nerve roots at spinal
cord level and also due to lack of sheaths around the nerves.
• Greater the vascularity, greater is the absorption
Local Anaesthetic Drugs
1. Cocaine:
• Causes CNS stimulation
• First anesthetic used
• On eye- mydriasis
• Used as 4% strength - only for topical analgesia
• Not metabolised by pseudo cholinesterase
• Potent vasoconstriction (not given i.v)
2. Procaine:
• 1-2 % concentration - nerve blocks
• Metabolised by pseudo cholinesterase
• Local anaesthetic of choice in malignant hyperthermia
• Interacts with sulphonamide antibiotics due to structural similarity to PABA
3. Chlorprocaine:
• Shortest acting ester
• Was out of use due to nerve toxicity
• Toxicity due to preservative
• Now in use for short acting property in day care surgeries
4. Prilocaine
• Used in Bier’s block
• Short acting - use - day care surgery
• Similar to lignocaine, but metabolism is extra hepatic ( metabolised in kidney and
lungs by amidase
• Metabolic product - Ortho toludine - can cause methemoglobinemia
5. Lignocaine:
• Most commonly used for nerve blocks
• Was used in spinal anaesthesia- not used now - transient neurological symptoms
• Dose: 4.5 mg/kg body weight (3.5 to 5)
• With adrenaline - 7mg/kg
• Used in treatment of ventricular arrhythmia
• On metabolism - produce MEG-x (mono ethyl glycine xylidide )
• Depends on liver blood flow for metabolism
6. Bupivacaine:
• Long acting
• Used in spinal anesthesia
• Good differential blockade - labour analgesia
• Dose - 2-3 mg/kg
7. Levobupivacaine:
• s. Isomer of bupivacaine
• Less cardiac and near toxicity
8. Ropivacaine:
• Less cardiac toxicity (than levobupivacaine)
• Less potent
• Preferred for Labour analgesia
Agnets not used routinely

1. Dibucaine: most potent, longest acting, most toxic

2. Meperidine: used in patients allergic to amides and esters

3. Etiodocaine: good surgical relaxation

EMLA Cream
• Eutectic mixture of LA
• Mixture having its melting point less than melting point of individual components
• Contains lignocaine 2.5% +prilocaine 2.5%mixed at 25 degree C to form oil in water
emulsion
• Used for surface anesthesia
• Indication- Skin biopsy/ grafting
Venepucture in children’s arterial puncture

Removal warts

Surgical debridement of leg ulcer

Circumcision
New trends in local anaesthetic

1. Tumescent aesthetic:
• For liposuction
• Large volumes of very diluted lignocaine + adrenaline + hyaluronidase
• Max dose of lignocaine - 35 to 55 mg/kg
• Liposomal encapsulation
2. Synera
• S- caine : lignocaine + tetracaine
• For topical application
 Pregnancy

• Spread of neuroaxial aesthesia more rapid in pregnant mother

• Mechanical effect- dilated epidural vessels, decreases subarachnoid space
• Direct effect - hormones - more susceptibility of nerve in conduction block
• LA drug dose to be decrease in all stages of pregnancy
Clinical Pharmacology
• Concern with potency, speed of onset, duration of action and differential sensory and
motor blockade
• All LA are synthetic compound except cocaine
• Free base is insoluble in water and soluble in lipids and lipid solvents
• Lowers surface tension
• No cross tolerance or cross sensitisation between esters and amides
• Rate of systemic absorption- more potent lipid soluble LA are associated with slower
rate of absorption
 Carbonation and pH Adjustment

• Addition of sodium bicarbonate

1. Accelerate onset

2. Decrease minimum concentration of drug

• Addition of sodium bicarbonate -
Increases pH which increases the amount of drug in the uncharged base - so the rate of
diffusion across nerve sheath - rapid onset of anesthesia
Toxicity of local Anesthetics
1. CNS:
• Tingling and numbness in perioral region
• Flickering of lights
• Halos
• Convulsions movements( seizures )
• Eg : Lignocaine
2. CVS:
• Arrhythmias, increase PR interval and QRS complex
• Decrease depolarisation rate in fast conducting tissues and purkinje fibres
• Eg: Bupivacaine - arrythmia caused by this drug is resistant to treatment
3. Minor Effects :
• Methemoglobinemia- seen with large doses of prilocaine, benzocaine
• Local toxicity - if injected directly into nerve
• Allergic reaction-common with esters
 Treatment of Toxicity
• Call for help - stop injecting
• ABC- 100% oxygen, intubate, IV access
• Control seizures
• CPR if indicated following standard protocol
• Consider treatment with lipid emulsion :
IV bolus 20% intralipid 1.5ml/kg over 1 min. Start an intravenous infusion of Intralipid
@ 20% at 0.25 ml/kg/min. Give two further boluses if necessary.

Increase infusion rate of Intralipid @20 % to 0.5 ml/kg/min if necessary

Thank You