local anaesthesia and local anaesthetics

1. L0CAL ANAESTHETICS AND LOCAL ANAESTHESIA
BY :DR. RAJESH CHOUDHURI
PGT, DEPARTMENT OF ANAESTHESIOLOGY
MODERATOR: Dr. V. MAJUMDER, Asst. Prof
AGMC & GBP HOSPITAL, AGARTALA

2. OBJECTIVES
• Introduction.
• History.
• Uses of local anaesthetics.
• Structure and classification.
• Mechanism of effect.
• Clinical pharmacology ( Pharmacokinetics and pharmacodynamics)
• Factors influencing the action of LAs.
• Effects on organ system and toxicity.
• Management of severe local anaesthetic toxicity .
• Measures to prevent local anaesthetic toxicity.

3. INTRODUCTION
• Local anesthetics—that produces transient loss of sensory, motor, and autonomic
function in a specific part of the body when the drugs are injected or applied in
proximity to neural tissue- without loss of conciousness.
• Prosperities of ideal LA
Reversible action.
Non-irritant.
No allergic reaction.
No systemic toxicity.
Rapid onset of action.
Sufficient duration of action.
Potent.
Stable in solutions.
Not interfere with healing of tissue.
Have a vasoconstrictor action or compatible withVC.
Not expensive

4. HISTORY
• The first LA, cocaine, was isolated in 1860.
• Cocaine introduced into practice in 1884 as a topical
ophthalmic anesthetic.
• Despite its addictive property, cocaine was used for 30
years.
• In 1905 procaine was synthesized, which became the
dominant LA for the next 50 years.
• Lidocaine, which is still a widely used LA, was
synthesized in 1943

5. USE OF LOCAL ANAESTHETICS
• Local anesthesia. Six Placement Sites are:
1.Surface/topical anesthesia,
2.Local infiltration,
3.peripheral nerve block,
4. Bier block (IV regional anesthesia),
5.Epidural anesthesia,
6. Spinal anesthesia
• Ventricular arrhythmia.
• Decrease haemodynamic response to tracheal intubation also decrease
cough.
• Treatment of epileptic fits.

6. STRUCTURE AND CLASSIFICATION
Ester-linked
Short acting, less stable in solution
Metabolized in the plasma and tissue fluids
by cholineestarase to produce PABA.
May cuase allergic reaction.
Excreted in urine
Amide-linked
Longer acting, heat stable
Metabolized by liver microsomal P450 enzymes
Rarely cause allergic reaction
Excreted in urine
ALL LOCAL ANAESTHETICS ARE WEAK BASES

7. Agent
Techniques
Maximum
Dose
(mg/kg)
Typical
Duration of
Neural
Blockade1
(h)
Benzocaine Topical NA2 0.5–1
Chloroprocaine Epidural, infiltration, peripheral nerve block 12 0.5–1
Cocaine Topical 3 0.5–1
Procaine Spinal, infiltration, peripheral nerve block 12 0.5–1
Tetracaine
(amethocaine)
Spinal, topical 3 1.5–6
EXAMPLE AND CLINICAL USE OF ESTERS

8. Agent Techniques
Maximum Dose
(mg/kg)
Typical Duration of
Neural Blockade1 (h)
Bupivacaine Epidural, spinal,
infiltration, peripheral
nerve block
3 1.5–8
Lidocaine (lignocaine) Epidural, spinal infiltration,
peripheral nerve block,
intravenous regional,
topical
4.5 0.75–2
7 (with epinephrine)
Mepivacaine Epidural, infiltration,
peripheral nerve block
4.5 1–2
7 (with epinephrine)
Prilocaine Peripheral nerve block
(dental)
8 0.5–1
Ropivacaine Epidural, spinal,
infiltration, peripheral
nerve block
3 1.5–8
EXAMPLE AND CLINICAL USE OF AMIDES

9. MECHANISM OF ACTION OF LAs
• Primary target of action: voltage gated sodium channels in the phospholipid bilayers
encapsulating neurons.
• Lipid soluble non-ionised LAs diffuse across the neural sheath to gain access to the
cytoplasm changed to cation form gain access to the open channel from
inside of the cell bind a specific region of the α subunit ofVASC
Prevent channel activation inhibit Na+ influx prevent generation of
action potential.
• As the conc. of LAs increases, the height of the AP reduced, the firing threshold
elevated, the spread of impulse conduction slowed and the refractory period
lengthened. Finally nerve conduction is completely blocked.
• Las are “use-dependant” blockers.

10. MECHANISM OF ACTION OF LAs

11. PHARMACOKINETICS
• More important determinants of elimination and toxicity than desired clinical effect.
• ABSORPTION
Most mucous membranes provide a weak barrier to local anesthetic penetration.
Intact skin requires a high water concentration for its penetration and a high
concentration of lipid-soluble local anesthetic base to ensure analgesia.
Systemic absorption of injected local anesthetics depends on :
1) Site of Injection: vascularity of the site of injection: intravenous > tracheal >
intercostal > caudal > paracervical > epidural > brachial plexus > sciatic >
subcutaneous.
2) Presence ofVasoconstrictors : The effects of vasoconstrictors are more
pronounced with shorter-acting agents.
3) Local Anesthetic Agent: highly tissue bound are more slowly absorbed.

12. PHARMACOKINETICS
• DISTRIBUTION
• Depends on the following factors:
1) Tissue Perfusion: The highly perfused organs (brain, lung, liver, kidney, and heart) are
responsible for the initial rapid uptake ( α phase), which is followed by a slower redistribution ( β phase) to
moderately perfused tissues (muscle and gut).
2)Tissue/Blood Partition Coefficient: Strong plasma protein binding tends to retain anesthetic
in the blood, whereas high lipid solubility facilitates tissue uptake.
3) Tissue Mass: Muscle provides the greatest reservoir for local anesthetic agents
• METABOLISM AND EXCRETION
1)Esters: metabolized by pseudocholinesterase , metabolites are excreted in the urine. ( except
Cocaine).
Procaine and benzocaine are metabolized to p-aminobenzoic acid (PABA).
2) Amides: metabolized (N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the
liver. Much slower than ester hydrolysis. Depends on the specific agent.
Metabolites of prilocaine (o-toluidine derivatives), which accumulate after large doses of
drug (> 10 mg/kg), convert hemoglobin to methemoglobin.

13. FACTORS INFLUENCING THE ACTION OF LA
1. Lipid solubility: more lipid solubility-more potency.
2. Aromatic ring and alkyl group: larger the alkyl group-more lipid solubility-more potency. ( eg.
Tetracaine vs. procaine, Bupivacaine vs. Mepivacaine)
3. Size, type and myelination of nerve fibre: order of blocking nerve fibres-(i) Autonomic
preganglionic B fibres ; (ii) temperature fibres-cold before warm; (iii) pin prick fibres; (iv) fibres coveying pain
greater than pin prick; (v) touch fibres; ( vi) deep pressure; (vii) somatic motor fibres; (viii) vibratory sense
and propioception.
4. PH : acidic PH antagonizes block. ( eg. Infectected tissue).
5. Frequency of nerve stimulation.
6. Electrolyte concentration: hypokalaemia and hypercalcaemia antagonizes block.
7. pKa : Local anesthetics with a pKa closest to physiological pH generally have a more rapid onset.

14. FACTORS INFLUENCING THE ACTION OF LA
8. Onset of action : depends on lipid solubility and pKa. Less potent , less lipid soluble agents
generally have a faster onset than more potent, more lipid soluble agents.
9. Duration of action: correlates with potency and lipid solubility. Highly lipid-soluble local
anesthetics have a longer duration of action.
10. Commercial formulation with epinephrine: they have slower onset of action comparing
to to the ‘plain’ solution.
11. Tachyphylaxis: decereased efficacy of repeated doses.
12. Alkalinization of the LA solution: speeds the onset and improves the quality of block. Also
decreases pain during subcutaneous infiltration. Done by adding 1 ml 8.4% sodium
bicarbonate per 10 ml local anaesthetic.

15. EFFECTS ON ORGAN SYSTEM AND TOXICITY
1. Central nervous system: central stimulation followed by depression.
Early symptom-circumoral numbness,tongue paresthesia, dizziness,tinnitus and blurred vision. Excitatory signs-
restlessness, agitation,nervousness, garrulousness and a feeling of impending dome, seizure. At higher doses-coma
and respiratory failure.
Neurological deficit, cauda equina syndrome, transient neurological symptoms.
2. Respiratory toxicity: may cause respiratory depression progressing to apnoea.—delayed onset.
Lidocaine depresses hypoxic drive.
3. Cardiovascular system: depresses myocardial autimaticity. At higher concentration-depresses myocardial
contractility and conduction velocity. All except cocain cause arteriolar vasodilatation.
At still increased concentration arrhythmia, heart block, depressed ventricular contractility and
hypotension may lead to cardiac arrest.
4. Immunological: esters may induce a true allergic reaction. Amides due to presence of Methylparaben may cause
allergic reaction.
5. Musculoskeletal: mildly myotoxic.
6. Hematological:lidocaine mildly depresses normal blood coagulation and enhnace fibrinolysis of whole blood.

16. Management of severe local anaesthetic toxicity: AAGBI safety guideline
1. RECOGNITION:
-Sudden alteration of mental status, severe agitation or loss of consciousness, with or without
tonic-clonic convulsions.
-Cardiovascular collapse: sinus bradycardia, conduction blocks, asystole and ventricular
tachyarrhythmias.
2. IMMEDIATE MANAGEMENT:
-Stop injecting the LA.
-Call for help.
-Maintain the airway and, if necessary, secure it with a tracheal tube.
-Give 100% O2 and ensure adequate lung ventilation.
-Confirm or establish IV access.
-Control seizures: give a benzodiazepine, thiopental or propofol in small increamental doses.
-Assess cardiovascular status throughout.
-Consider drawing blood for analysis, but do not delay definitive treatment to do this.

17. Management of severe local anaesthetic toxicity: AAGBI safety guideline
3.TREATMENT:
IN CIRCULATORYARREST WITHOUT CIRCULATORYARREST
Start CPR using standard protocol.
Manage arrhythmia using the same protocols ,
recognizing that arhrythmia may be very
refractory.
Consider the use of CPB if available.
Consider lipid emulsion
ContinueCPR with lipid emulsion.
Recovery may be > 1 hr.
Use conventional therapies to treat:
Hypotension, bradycardia, tachyarrhythmia.
Consider lipid emulsion
Propofol is not a suitable substitute for lipid
emulsion.

18. Management of severe local anesthetic toxicity: AAGBI safety guideline
• FOLLOW UP :safe transfer to a clinical area with appropriate equipment and suitable
staff until sustained recovery is achieved.
Exclude pancreatitis by regular clinical review, including daily amylase or lipase
assays for two days.
• INTRALIPID DOSES:
Immediately: an initial IV bolus inj. of lipid emulsion @ 1.5 mi/kg over 1min and
start an IV infusion of 20% lipid emulsion @ 1.5 ml/kg/ hr.
After 5 min: a max. of two repeat boluses at 5 min interval ( same dose) if
cardiovascular stability has not been restored .
A maximum of 3 boluses can be given( including initial bolus)
AND continue infusion at same rate, but double the rate at any time
after 5 min, if cardiovascular stability has not been restored .
Continue infusion until stable or maximum dose of lipid emulsion
given.

19. MEASURES TO PREVENT SEVERE LA TOXICITY
1. Perform RA in an area equipped to deal with cardiorespiratory collapse.
2. The age, weight and infirmity of the patient should be taken into account,
and doses adjusted accordingly.
3. Clear labeling of syringes.
4. Gentle aspiration of the syringes before every injection.
5. Keep talking to the patient– both during and after drug administration.
6. Appropriate test dosing depending on the situation.
7. USG guided nerve block– if available.