Local Anaesthetics
Dr S. I. Ozomma, MBBS, FMCP
Consultant Neurologist
University of Calabar Teaching Hospital
Local anaesthetics (LAs)
• 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.
• They block generation and conduction of nerve
impulse at any part of the neurone with which they
come in contact, without causing any structural
damage.
• 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.
Comparative features of general and local
anaesthesia
Classification of Local anaesthetics (LAs)
1. Injectable anaesthetic
• Low potency, short duration; Procaine, Chloroprocaine
• Intermediate potency and duration; Lidocaine(Lignocaine), Prilocaine
• High potency, long duration; Tetracaine (Amethocaine), Bupivacaine,
Ropivacaine, Dibucaine (Cinchocaine)
2. Surface anaesthetic
• Soluble; Cocaine, Lidocaine, Tetracaine, Benoxinate
• Insoluble; Benzocaine, Butylaminobenzoate (Butamben), Oxethazaine
• Mepivacaine, Etidocaine, Articaine, Dyclonine, Proparacaine are other
local anaesthetics, occasionally used
• Local anaesthesia can be produced by cooling as well, e.g. application
of ice, CO2 snow, ethylchloride spray.
• The clinically useful LAs
are weak bases with
amphiphilic property. A
hydrophil or tertiary
amine on one side and
a lipophilic aromatic
residue on the other are
joined by an alkyl chain
through an ester or
amide linkage
Structural classification of Features of amide LAs (compared to
ester LAs)
LAs
• Ester-linked LAs Cocaine, • Produce more intense and
procaine, chloroprocaine, longer lasting anaesthesia
tetracaine, benzocaine. • Bind to α1 acid glycoprotein
in plasma
• Not hydrolysed by plasma
• Amide-linked LAs esterases
Lidocaine, bupivacaine, • Rarely cause
dibucaine, prilocaine, hypersensitivity reactions;
ropivacaine no cross sensitivity with
ester LAs
Because of their short duration, less intense analgesia and
higher risk of hypersensitivity, the ester-linked LAs are rarely
used for infiltration or nerve block, but are still used topically on
mucous membranes.
MECHANISM OF ACTION
• The LAs block nerve conduction by decreasing the entry of Na+
ions during upstroke of action potential (AP). As the concentration
of the LA is increased, the rate of rise of AP and maximum
depolarization decreases
• Potency of a LA generally corresponds to the lipid solubility of its
base form, because it is this form which penetrates the axon.
• However, the predominant active species is the cationic form of
the LA which is able to approach its receptor only when the
channel is open at the inner face, and it binds more avidly to the
activated and inactivated states of the channel, than to the resting
state.
• The onset time of blockade is related primarily to the pKa of the
LA. Those with lower pKa (7.6–7.8), e.g. lidocaine, mepivacaine are
fast acting
LOCAL ACTIONS
• The clinically used LAs have no/minimal local irritant
action and block sensory nerve endings, nerve
trunks, neuromuscular junction, ganglionic synapse
and receptors (non-selectively), i.e. those structures
which function through increased Na+ permeability.
• Injected around a mixed nerve they cause
anaesthesia of skin and paralysis of the voluntary
muscle supplied by that nerve.
• Myelinated nerves are blocked earlier than
nonmyelinated
The LA often fails to afford adequate pain
control in inflamed tissues
• The likely reasons are:
• a. Inflammation lowers pH of the tissue— greater
fraction of the LA is in the ionized form hindering
diffusion into the axolemma.
• b. Blood flow to the inflamed area is increased—
the LA is removed more rapidly from the site.
• c. Effectiveness of Adr injected with the LA is
reduced at the inflamed site.
• d. Inflammatory products may oppose LA action.
Addition of a vasoconstrictor, e.g. adrenaline
(1:50,000 to 1:200,000):
• Prolongs duration of action of LAs by decreasing their rate of
removal from the local site into the circulation: contact time of the
LA with the nerve fibre is prolonged.
• Enhances the intensity of nerve block.
• Reduces systemic toxicity of LAs: rate of absorption is reduced and
metabolism keeps the plasma concentration lower.
• Provides a more bloodless field for surgery.
• 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.
• May raise BP and promote arrhythmia in susceptible individuals.
SYSTEMIC ACTIONS
• All LAs are capable of producing a sequence of stimulation followed by
depression
• Early neurological symptoms of overdose with lidocaine and other
clinically used LAs include, abnormal sensation in the tongue, dizziness,
blurred vision, tinnitus followed by drowsiness, dysphoria and lethargy.
• Still higher doses produce excitation, restlessness, agitation, muscle
twitching, seizures
• LAs are cardiac depressants, but no significant effects are observed at
conventional doses
• LAs tend to produce fall in BP.
• However, Cocaine has sympathomimetic property; increases
sympathetic tone, causes local vasoconstriction, marked rise in BP and
tachycardia
PHARMACOKINETICS
• Because LAs act near their site of administration,
pharmacokinetic characteristics are not important
determinants of their efficacy, but markedly influence their
systemic effects and toxicity.
• Procaine is negligibly bound to plasma proteins, but amide LAs
are bound to plasma α1 acid glycoprotein.
• Ester-linked LAs (procaine, etc.) are rapidly hydrolysed by
plasma pseudocholinesterase and the remaining by esterases
in the liver.
• Amide-linked LAs (lidocaine, etc.) are degraded only in the
liver microsomes by dealkylation and hydrolysis
• After oral ingestion both procaine and lidocaine have high first
pass metabolism in the liver. Thus, they are not active orally
for antiarrhythmic purposes
ADVERSE EFFECTS
• (1) CNS effects are light-headedness, dizziness auditory and visual
disturbances, mental confusion, disorientation, shivering, twitchings,
involuntary movements, finally convulsions and respiratory arrest. This
can be treated with 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..
• (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.
Precautions and interactions
• 1. Before injecting the LA, aspirate lightly to avoid
intravascular injection.
• 2. Inject the LA slowly and take care not to exceed the
maximum safe dose, especially in children.
• 3. Propranolol (probably other β blockers also) may reduce
metabolism of lidocaine and other amide LAs by reducing
hepatic blood flow.
• 4. Vasoconstrictor (adrenaline) containing LA should be
avoided for patients with ischaemic heart disease, cardiac
arrhythmia, thyrotoxicosis, uncontrolled hypertension, and
those receiving β blockers (rise in BP can occur due to
unopposed α action) or tricyclic antidepressants (uptake
blockade and potentiation of Adr).
Comparative properties of important local
anaesthetics
USES AND TECHNIQUES OF LOCAL
ANAESTHESIA
• 1. Surface anaesthesia
• 2. Infiltration anaesthesia
• 3. Conduction block
• (a) Field block
• (b) Nerve block
• 4. Spinal anaesthesia
• 5. Epidural anaesthesia
• (i) Thoracic
• (ii) Lumbar
• (iii) Caudal
Sites and uses of surface anaesthesia
Drugs used for spinal anaesthesia
and their duration of action
Contraindications to spinal anaesthesia
• Hypotension and hypovolemia.
• Uncooperative or mentally ill patients.
• Infants and children—control of level is
difficult.
• Bleeding diathesis.
• Raised intracranial pressure.
• Vertebral abnormalities e.g. kyphosis, lordosis
• Sepsis at injection site.
Complications of spinal anaesthesia
• 1. Respiratory paralysis
• 2. Hypotension
• 3. Headache
• 4. Cauda equina syndrome
• 5. Septic meningitis
• 6. Nausea and vomiting
