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1. LOCAL ANAESTHETICS
Dr Wairimu Mwaura

2. OBJECTIVES
 What are local anaesthetics?
 Mechanism of action of LA
 Classification of LA
 Pharmacokinetics of LA
 Pharmacodynamics of LA
 Local anaesthesia systemic toxicity and its
management
 Techniques of local anaesthesia

3. LOCAL ANAESTHETICS
 LA are drugs which produce a transient and
reversible loss of sensation in a circumscribed
region of the body without loss of
consciousness.
 LA are widely used for the provision of
anaesthesia and analgesia.

4. STRUCTURAL CLASSIFICATION
 Local anaesthetics have :
i. Lipid soluble hydrophobic aromatic group
ii. Intermediate chain (ester/ amide)
iii. Charged hydrophilic amide group

5. STRUCTURAL CLASSIFICATION OF LA

6. STRUCTURAL CLASSIFICATION OF LA

7. LA CLASSIFICATION
Injectable local anaesthetic:
♦ Low potency,short duration: procaine,chlorprocaine
♦ Intermediate potency: Lignocaine, prilocaine
♦ High potency, long duration: bupivacaine, ropivacaine
Surface anaesthetic:
♦ Soluble : cocaine, lignocaine, tetracaine
♦ Insoluble : benzocaine, procaine, chloroprocaine

8. MECHANISM OF ACTION
LA disrupt Na+ ion channel function preventing
the initiation and propagation of the neuronal
action potential.
Occurs in two ways:-
i. Ionised form of the LA binds to the sodium
channel and holds it in an inactive state so that
no further depolarisation can occur.
ii. Membrane expansion theory: unionised LA
molecules are incorporated into the cell
membrane disrupting ion channel function.

9. MECHANISM OF ACTION

10. PHARMACODYNAMICS
LA are weak bases.
Predominantly ionised an neutral ph.
Structure : esters or amides
Esters are less stable in solution cannot be
stored as long as amides.
Amides are heat stable, can be autoclaved.

11. PHARMACODYNAMICS
Lipid solubility: determines the potency of a LA.
♦ A LA that is more lipid soluble will have more of its molecules
penetrate the nerves, therefore less drug is required to give the same
blockade
Protein binding: affects the duration of action.
The more protein bound = the longer the duration of action as free drug
is more slowly made available for metabolism
Bupivacaine is 95% protein bound, lignocaine 65%.
Duration of action bupivacaine= > 180 minutes, lignocaine= 45-75
minutes.
Length of the intermediate chain, intrinsic vascular effects of the drug
and total dose given also affect duration.

12. PHARMACODYNAMICS
Pka: determines speed of onset of action of LA.
♦ The closer the pka of the LA is to physiological ph the greater
the amount of non ionised drug present and the faster the onset
of the block.
♦ Lignocaine pka is 7.9 , 25% unionised onset within 1.5 minutes
♦ Bupivacaine pka 8.1,15% unionised onset within 5 minutes

13. PHARMACODYNAMICS
Local vascular effects: Majority of LA are
vasodilators except cocaine, ropivacaine and
levobupivacaine.
Degree of vasodilation influences the toxicity and potency of LA.
Vasodilation= systemic absorption, less drug is available for
neural blockade.
Cocaine causes vasoconstriction by inhibiting neuronal uptake
of catecholamines.

14. PHARMACOKINETICS OF LA
ABSORPTION
LA are administered to the areas around the
nerves to be blocked.
This includes: skin, subcutaneous tissue,
mucous membranes, intrathecal and epidural
spaces.
Absorption into the systemic circulation depends
on:
i. Local anaesthetic agent used
ii. Additives such as vasoconstrictors
iii. Vascularity at the site of injection

15. ABSORPTION OF LOCAL ANAESTHETICS

16. PHARMACOKINETICS OF LA
DISTRIBUTION
Influenced by tissue and plasma protein binding.
Esters are minimally bound while amides are
more extensively bound.
LA are bound to α 1 glycoprotein..

17. METABOLISM AND EXCRETION
ESTERS
Broken down rapidly by plasma esterases to
inactive compounds.
Short elimination half life due to rapid hydrolysis.
Metabolism results in the production of para-
amino benzoate (PABA) which is associated
with allergic reactions.
Cocaine unlike other esters undergoes hepatic
hydrolysis.
Ester metabolites are excreted in the urine.

18. METABOLISM AND EXCRETION
AMIDES
Metabolised in the liver by amidases.
Slower process, metabolites can accumulate if
given in repeated doses or infusion.
Reduced metabolism in hepatic dysfunction.
Prilocaine is metabolised in the liver, kidney and
lungs.
O-toludine may precipitate methaemoglobinaemia.
Metabolites are excreted in urine.

19. CLINICAL ASPECTS
Order of blockade: pain >temperature >touch
and pressure > motor function. Recovery is
reverse pain sensation returns last.
Onset of anaesthesia : determined by pka
Duration of anaesthesia:protein binding
Concomitant use of a vasoconstrictor
prolongation of anaesthesia+ toxicity.
Inflammation: susceptibility to anaesthesia
lowered local ph increases proportion of ionised
LA that cannot permeate the nerve membrane.

20. LOCAL ANAESTHETICS AND ADDITIVES
Additives are used in conjunction with local
anaesthetics to:
i. Quicken onset of anaesthesia:bicarbonate
ii. Prolong duration of anaesthesia: epinephrine
iii. Enhance anaesthesia: morphine, fentanyl

21. LOCAL ANAESTHETICS AND ADDITIVES

22. LIGNOCAINE
Rapid onset: 3minutes, pka 7.9 with 25%
unionised.
Moderate duration of action: 65% protein bound
Less toxic than bupivacaine.
Available as injection (0.5-2%), spray (4-10%),
gel (1-2%), ointment (5%), medicated plaster.
Available as 1%& 2% solutions with / without
adrenaline.
Uses : topical, infiltration, spinal, chronic

23. BUPIVACAINE
Slower onset: pka 8.1 , 15% unionised
Greater potency; more lipid soluble
Longer duration of action: 95% pp bound
compared to 65% lignocaine
Greater cardiac toxicity binds avidly to cardiac
muscle.
Contraindicated for IV regional anaesthesia.
Uses: infiltration, spinal, epidural, nerve block.
No topical effect.

24. PRILOCAINE
Used for intravenous regional anaesthesia.
Presented as a 0.5-2% colourless solution.
Fast onset:pka of 7.7, 33 % unionised.
Moderate duration of action, protein binding
55%
Metabolised in the liver,kidneys and lungs
Dose : plain 5mg/kg
with adrenaline 8mg/kg
Maximum single dose:400mg

25. LOCAL ANAESTHETIC USES
1. Surface / topical
anaesthesia
2. Local infiltration
3. Peripheral nerve
blocks
4. Intravenous regional
anaesthesia ( Biers
block)
5. Spinal anaesthesia
6. Epidural anaesthesia

26. 1.SURFACE / TOPICAL ANAESTHESIA
Application to mucous
membranes.
Cocaine 4-10%: ENT
cases, causes
vasoconstriction

27. 1.SURFACE /TOPICAL ANAESTHESIA
Lignocaine
oxymetazoline
Tetracaine 1-2%
Nebulised lignocaine
for intractable coughs,
prior to bronchoscopy
Procaine and
chloroprocaine poor
mucous membrane
penetration.

28. 1.SURFACE /TOPICAL ANAESTHESIA
EMLA: eutectic mixture of local anaesthetics.
The melting point of the mixture is lower than
the melting point of the individual components.
Contains 2.5% lignocaine and 2.5% prilocaine.
Available as a cream/ patch.
Dermal anaesthesia achieved within 60 minutes
and lasts two hours.
Prevent pain associated with IV insertion,blood
sampling, superficial surgical procedures .
Topical anaesthesia for leg ulcers: debridement

29. EMLA

30. 2. LOCAL INFILTRATION
Application of LA subcutaneously to
anaesthetise distal nerve endings.
Uses : suturing, CVC placement, minor
superficial surgery.
Most commonly used: Lignocaine
Others: bupivacaine/ ropivacaine
Epinephrine containing LA solution should not
be injected into tissues containing end arteries:
fingers, toes ,ear lobes, nose.

31. 3. BIERS BLOCK
Injection of LA into the venous system of the
upper or lower limb that has been
exsanguinated and isolated from the central
circulation.
Uses : surgery below the elbow and knee.
Advantages: rapid onset and recovery,easy to
administer, low incidence of block failure.
Disadvantages: LA toxicity,tourniquet
pain,difficulty in providing a bloodless field.

32. BIERS BLOCK

33. 4. PERIPHERAL NERVE BLOCK
Injecting LA near the course of a named nerve.
Uses: surgical procedures in the distribution of
the blocked nerve.
Advantages : small dose of LA to cover a large
area, rapid onset.
Disadvantages :neuropathy, technical
complexity

34. 4. PERIPHERAL NERVE BLOCK

35. 4. PLEXUS BLOCKADE
Injection of LA next to a plexus: brachial, lumbar
Provide surgical anaesthesia and analgesia in
the distribution of the plexus.
Advantages ; large area of anaesthesia with
relatively small dose of LA
Disadvantage: neuropathy, potential for toxicity,
technical complexity

36. PLEXUS NERVE BLOCK

37. 5. SPINAL ANAESTHESIA
Anaesthesia following injection of LA into the
lumbar subarachnoid space.
Provides profound anaesthesia of the lower
abdomen and extremities.
Advantages : rapid onset, high success rate
Disadvantages :post dural puncture headache,
hypotension

38. SPINAL ANAESTHESIA

39. 6. EPIDURAL ANAESTHESIA
Injection of LA into the epidural space.
Uses : anaesthesia + analgesia of the thorax,
abdomen and lower extremities
Advantages: post operative analgesia,controlled
onset of blockade.
Disadvantages : post dural puncture headache,
LA toxicity, technically complex

40. EPIDURAL ANAESTHESIA

41. ADVERSE EFFECTS OF LA
1. Methaemoglobinaemia
Prilocaine, lignocaine and benzocaine.
LA metabolites have significant oxidizing
properties.
Convert haemoglobin to methaemoglobin,
compromised O2 carrying ability.
Treatment: O2 administration,methylene blue

42. ADVERSE EFFECTS OF LA
2.Hypersensitivity
Common with ester linked LA
Rashes,dermatitis, angioedema, anaphylaxis.
3.Neurotoxicity
LA cause concentration dependent nerve
damage to central and peripheral NS.
Permanent neurological injury is rare.
May account for transient neurological
symptoms after spinal anaesthesia.

43. 4.LOCAL ANAESTHESIA SYSTEMIC TOXICITY
Toxicity is caused by
the intrinsic effects of
LA to block conduction
in all excitable tissues
especially in the CNS
and heart.
CNS is more sensitive
to toxic effects, signs
and symptoms
present first.

44. LOCAL ANAESTHESIA SYSTEMIC TOXICITY

45. RISK FACTORS FOR LAST
Administration at >
than recommended
dose.
Inappropriate use of
medical devices.
Proximal injection site
( intercostal > UL
block> head and
neck)
Use of high drug
volumes during

46. PREVENTION OF LAST
i. Adjust dose to patients age, weight and
physical condition.
ii. Gentle aspiration on the syringe prior to
injection.
iii. Labelling of syringes containing LA.
iv. Maintain verbal contact with the patient during
and after the procedure.
v. Use of ultrasound to perform nerve blocks.
vi. Regional blocks should be performed in an area
equipped to deal with cardiorespiratory collapse.

47. LAST MANAGEMENT

48. THANK YOU