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The following structure is common to all local anaesthetic agents

Aromatic ->Ester or Amide portion ->Amine portion
The two types of local anaesthetics differ with respect to their intermediate chain, which may contain an ester or an amide.
  1. Local anaesthetics work by blocking sodium channels
  2. The agent, a weak base, is injected as hydrochloride salt in an acid solution - tertiary amine group becomes quaternary and suitable for injection (i.e. dissolves in solution).
  3. Following injection, the pH increases (due to the higher pH of the tissues, which is usually 7.4) and the drug dissociates, the degree of which depends on pKa, and free base is released.
  4. Lipid soluble free base enters the axon. Inside the axon the pH is lower (because the environment is more acidic), and re-ionization takes place.
  5. The re-ionized portion enters the Na+ channels and blocks them, preventing depolarization
Classification of LA
  Esters Amides
Short acting procaine
Intermediate acting   lignocaine
long acting tetracaine

Classification of LA

  1. Injectable anaesthetic
    1. Low potency, short duration
      1. Procaine
      2. Chloroprocaine
    2. Intermediate potency and duration
      1. Lidocaine (Lignocaine)
      2. Prilocaine
    3. High potency, long duration
      1. Tetracaine (Amethocaine)
      2. Bupivacaine
      3. Ropivacaine
      4. Dibucaine (Cinchocaine)
  2. Surface Anaesthetic
    1. Soluble 
      1. Cocaine
      2. Lidocaine
      3. Tetracaine
      4. Benoxinate
    2. Insoluble
      1. Benzocaine
      2. Butyl amino benzoate (Butamben)
      3. Oxethazaine

Ways of accelerating the speed of onset of blockade with a local anaesthetic

  1. Decreasing latency and prolongation of action of the local anaesthetic agent
    1. Alpha 1 agonists
      1. Noradrenaline (5mg/ml)
    2. Addition of a vasoconstrictor, e.g. adrenaline (1:50,000 to 1:200,000):
      1. Adrenalin (5mg/ml) (1:200 000) increases block by 50% and systemic absorption by 1/3
      2. Prolongs duration of action of LAs by decreasing their rate of removal from the local site into the circulation.
      3. Enhances the intensity of nerve block. Reduces systemic toxicity of LAs: rate of absorption is reduced and metabolism keeps the plasma concentration lower.
      4. Makes the injection more painful.
      5. Provides a more bloodless field for surgery.
      6. Increases the chances of subsequent local tissue edema and necrosis as well as delays wound healing by reducing oxygen supply and enhancing oxygen consumption in the affected area.
      7. May raise BP and promote arrhythmia in susceptible individuals.
    3. Alpha 2 agonist (clonidine) cause vasoconstriction and delay systemic absorption.
    4. Combination Alpha 1 and 2 agonist
    5. Addition of NaHCO3 (1ml per 10ml of lig and 0.1ml per 10ml of bup) raises local pH thus increasing the unionized % and increases transfer across the lipid membrane .
    6. Warming the solution to 37oC possibly decreases the pKa of the local anaesthetic and hastens the onset
    7. Combining a short onset local anaesthetic with a long duration local anaesthetic should provide the best of both worlds. Mixtures of local anaesthetic show additive toxicities
    8. Combining a local anaesthetic with an opioid will lower the total amount and concentration of local anaesthetic necessary and increase the duration of the block itself.
    9. Addition of CO2 @ 700mmHg (carbonation) increases local CO2 concentration which passes into cells and decreases intracellular pH therefore increasing the ionized concentration and so promoting receptor binding.
    10. Time release preparations decrease the rate of release and increase the local availability of the local anaesthetic preparationsBiodegradable polyanhydride polymers for regional blockadeLipid depot in neuraxial blockade using iophendylateLiposomal encapsulation with egg yolk phosphatidyl choline and cholesterol in neuraxial blockade
    11. Local anaesthetics have preferential effects on any particular types of nerve fibre
      1. As a general rule of thumb, the greater the diameter of the nerve fibre, the greater the concentration of LA required to produce conduction blockade. Small unmyelinated fibres are more vunerable to blockade than large myelinated fibres.
      2. There is a progressive loss of function, for example with epidural anaesthesia, as the dose of the LA is increased in the following order:
Type of nerve Function Effect
B Pre-Ganglionic Autonomic Warm limb
C Pain and post ganglionic sym  
A-delta Pain & Temperature Loss of pain sensation
A-gamma Proprioception Loss
A-beta Touch and pressure Loss
A-alpha Motor Paralysis
  1. Bupivacaine 2mg/kg
  2. Lignocaine 3mg/kg
  3. Prilocaine 6mg/kg
Table: comparative properties of important local anaesthetics
Safe max*
dose (inj.)
(without Adr)
Metabolism in Duration of
nerve block
  surface injection toxic Onset plasma liver
Cocaine 1 1 1 not injected fast - + -
Procaine 1/10 1/2 1/6 6 slow + + 30-60
Lidocaine 1 2 1/6 4.50 fast   + 60-120
Tetracaine 4 10 2 1.2 slow + + 180-480
Bupivacaine - 10 2 1.5 interm.- + + 180-360
Dibucaine 6 15 3 1 slow   + 180-600

Side Effect Of LA

  1. CNS effects are light-headedness, dizziness, auditory and visual disturbances, mental confu­sion, disorientation, shivering, twitching, invo­luntary movements, finally convulsions and respiratory arrest. This can be prevented and treated by diazepam.
  2. Cardiovascular toxicity of LAs is manifested as bradycardia, hypotension, cardiac arrhyth­mias and vascular collapse.
  3. Injection of LAs may be painful, but local tissue toxicity of LAs is low. However, wound healing may be sometimes delayed. Addition of vasoconstrictors enhances the local tissue damage; rarely necrosis results. Vasoconstrictors should not be added for ring block of hands, feet, fingers, toes, penis and in pinna. Bupivacaine has the highest local tissue irritancy.
  4. Hypersensitivity reactions like rashes, angio­edema, dermatitis, contact sensitization, asthma and rarely anaphylaxis occur. These are more common with ester-linked LAs, but rare with lidocaine or its congeners. Cross reactivity is frequent among ester compounds, but not with amide-linked LAs.
CC/CNS ratio is 4 for bupivicaine, 7 for lignocaine

What is this CC/CNS ratio?

This is the ratio of dosage or blood levels required to produce irreversible cardiovascular collapse to that level required to produce convulsions. The lower the ratio, the more potentially hazardous the drug is. This is the reason why we don't use bupivicaine for iv regional blocks.

Important points

Naturally occurring,

Vasoconstrictor &

Earliest used


Vaso-ineffective, Causes

(neither dilator nor

Constrictor, Safest





so C/I in same


LA of choice in

Malignant hyperpyrexia



injections are

C/I &




  1. Local anaesthetics (LAs) are drugs which upon topical application or local injection cause rever­sible loss of sensory perception, especially of pain, in a restricted area of the body.
  2. They block generation and conduction of nerve impulse at all parts of the neuron where they come in contact, without causing any structural damage.
  3. Thus, not only sensory but also motor impulses are interrupted when a LA is applied to a mixed nerve, resulting in muscular paralysis and loss of autonomic control as well.
Toxicity depends on the amount of free drug in plasma this relates to three factors:
  1. Dose given
  2. Rate of injection (the effective dose given).
  3. Site of injection (the greater the blood supply to the area injected the greater the systemic absorption). Sites of absorption from greatest to least:
Intravascular > tracheal > interpleural > intercostal > pudendal > caudal > epidural > brachial plexus > infiltration


Extra Edge
Out of the four routes A. Intercostal B. Epidural C. Brachial D. Caudal,
The fastest route for absorption of LA is intercostal block, due to close location of blood vessel around the nerve, so that is why LA are rapidly taken by in intercostal block. (AIIMS Nov 08)


  1. A natural alkaloid – from leaves of Erythroxylon coca
  2. It is earliest used anaesthesia and first used for ocular anaesthesia in 1884
  3. Only ester LA which is not hydrolyzed by pseudocholine esterase.
  4. Should never be injected as it is protoplasmic poison.
  5. Unique among drug of abuse for not producing significant tolerance on repeated use.
    1. Cocaine stimulates Vagal centre– brady cardia
    2. Vasomolor centre – Hypertension
    3. Temperature Regulating centre– Pyrexia
    4. Vomitting centre– Nausea & Vomiting
  6. In periphery, it blocks uptake of NA and Adrenaline causing sympathomimetic effect.
    1. Local Vaso constriction
    2. Hypertension
    3. Tachycardia
    4. Mydriasis
  7. So it should not be used with adrenaline (increase chances of cardiac arrhythmias & V.F)


  1. 1st synthetic LA
  2. PABA is released on hydrolysis which can antagonize sulfonamides and PAS.
  3. Forms poorly soluble salt with Benzyl penicillin called as procaine penicillin, which on I.M injection acts for 24 hrs d/t slow absorption.
  4. LA of choice in Malignant hyperpyrexia


  1. Shortest acting LA
  2. Intradural injections are c/I as it may lead to paraplegia due to sodium metabisulfate which is a preservative in this LA.

Amethocaine (Tetracaine)

  1. Only agent which is completely hydrated in body and is not excreted.
  2. It is very toxic due to slow metabolism & may cause cardiac asystole and VF.
  3. Absorption from Tracheobronchial spray is very fast and concentration approach similar to that of iv injection. Therefore it is used for laryngeal block.

Lignocaine / Lidocaine / Xylocaine

  1. Most commonly used LA
  2. Vaso ineffective – Neither Vaso contrictor, Nor Vaso dilator
  3. No mydriasis & Cycloplegia
  4. Propranolol increases risk of toxicity by decreasing clearance
  5. Contraindicated in malignant hyperpyrexia and pt. with history of convulsion due to CNS toxicity.
  6. Used as DOC in – Ventricular Tachycardia
    - Ventricular Extra systole (VES)
    - In acute MI
    - Digitalis induced
  7. Dose in VT & VES is 1-15 mg/Kg /min
Lignocaine Conc.
5% 4% 0.5%
In spinal anaesthesia For topical use
- Eye

- Pharynx
Epidural Anaesthesia
Maximum Safest Dose  
With Adrenaline Without Adrenaline
7 mg/Kg or 500 mg 3 mg/Kg or 200 mg
  • S/E (twitching, convulsions, apnoea, cardiac arrest etc.) decreased by acidification of urine which increases excretion.


  1. Safest LA
  2. Causes maximum methemoglobinemia esp. over 600 mg of dose so C/I in congenital and acquired methemoglobinemia (AIIMS May 2009)
  3. Drugs causing methemoglobinemia. 1. Lignocaine, 2. Benzocane, 3. Prilocaine (PGI June 2005)
  4. Treatment of methemoglobinemia –
    1. DOC Methylene Blue, Dose 1 – 2 mg/Kg.
    2. Mechanism of Action of Methylene Blue converts Met Hb into Cyanomet Hb.
  5. Max safe dose 400 mg (5 mg/Kg), and with adrenaline 600 mg (8 mg/Kg)
  6. Most suitable for Bier’s block, also known as IVRA (I. V regional Anaesthesia)


  1. DOC for hyperbaric spinal Anaesthesia as it is most potent
  2. C/I in intravenous regional Anaesthesia, as it is most cardiotoxic (VT, cardiac depression)
  3. Very popular in obstetrics.
    1. Adequate analgesic without significant motor block, causes active co-operation of mother in vaginal delivery.
    2. High lipid solubility causes more conc. Of drug in tissue then in blood – so less likely to reach fetus and produce neonatal depression. (Due to low materno fetal transfer)
  4. Not used for surface Anathesia.
  5. Bupiva-caine is more prone to prolong QTc interval and induce ventricular tachycardia or cardiac depression should not be used for intravenous regional analgesia (Bier’s).
Levobupivacaine is equally potent butless cardiotoxic and less prone to cause seizures then bupiva caine.


  1. Newly developed bupivacaine congener with
    1. Less cardiotoxicity
    2. More degree of separation between sensory & motor block
  2. Also used in labour & post operative relief.


  1. Only agent which is most metabolized by neonates so C/I in labour and neonates.
  2. Only agent which resist Acid & Alkali hydrolysis.


  1. Unique in ionizing to a very small extent even at low pH values.
  2. So highly effective in anaesthetizing gastric mucosa.
  3. And useful in -
    1. Gastritis
    2. Gastroesophageal reflux
    3. Heart burn of pregnancy
  4. Decrease gastro colic reflex so reduce post prandial urgency in irritable Bowel syndrome.
Recent trends-
Ropivacaine (Naropin) is the pure S(-)-enantiomer of Propivacaine, and is a long-acting amide local anaesthetic agent,.
The efficacy of ropivacaine is similar to that of bupivacaine and levobupivacaine for peripheral nerve blocks and, although it may be slightly less potent than bupivacaine when administered epidurally or intrathecally, equi-effective doses have been established.
Clinically adequate doses of ropivacaine appear to be associated with a lower incidence or grade of motor block than bupivacaine.
Ropivacaine, with its efficacy, lower propensity for motor block and reduced potential for CNS toxicity and cardiotoxicity, an important option for regional anaesthesia and for the management of postoperative and labour pain.
Only LA which has    
Max retention in body

- Ionise very little at low pH
- Anaesthetise gastric mucosa
- Decrease gastro colic reflex

- DOC for isobaric anesthesia (spinal)
- C/I IV regional anesthesia


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