Introduction
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. LAs block nerve conduction of sensory impulses and
in higher concentrations block motor impulses from the periphery to the CNS.
Chemical aspects
LAs are weak bases with amphiphilic property. The molecules consist of an
aromatic part linked by an ester or amide bond to a basic side chain, they are
weak bases with pka values mainly in the range of 8-9, and consequently they
are mainly ionized at physiological PH.
Ester-linked LAs are: Benzocaine, Chloroprocaine, Cocaine, Procaine,
Tetracaine.
Amide linked LAs are: Bupivacaine, Lidocaine, Prilocaine, Mepivacaine
Ropivacaine.
The presence of the ester or amide bond in local anaesthetic molecules is
important because of its susceptibility to metabolic hydrolysis. Moreover, amide
local anaesthetics have the following features over the ester group of local
anaesthetics.
a. Produce more intense and longer lasting anaesthesia
b. Bind to α1 acid glycoprotein in plasma
c. Not hydrolysed by plasma esterases
d. Rarely cause hypersensitivity reactions, 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. They are however, used topically on mucous membranes.
Mechanism of action
Local anaesthetics block the initiation and propagation of action potentials by
preventing the voltage dependent increase in Na+ conductance.
Local anaesthetic activity is PH dependent, being increased at alkaline PH(that
is when the proportion of ionized molecules is low) and vice versa. This is
because the compound needs to penetrate the nerve sheath and the axon
membrane to reach the inner end of the sodium channel, because the ionized
form is not membrane permeant, penetration is very poor at acid PH. The onset
of action of local anaesthetics is influenced by several factors including tissue
pH, nerve morphology, concentration, PKa and lipid solubility of the drug.
Among all these, the PKa is most important. LAs with a lower PKa have a
quicker onset since more drug exists in the unionized form at physiologic pH,
thereby allowing penetration of the nerve cell membrane. Once at the nerve
membrane, the ionized form interacts with the protein receptor of the Na +
channel to inhibit its function and achieve local anasthecisic
Pharmacokinetics
Soluble surface anaesthetics (lidocaine, tetracaine) are rapidly absorbed from
the mucous membranes and abraded area, however absorption from intact skin
is poor.
Ester linked LAs are rapidly hydrolysed by plasma pseudocholinesterase and
the remaining by esterases in the liver.
Amide-linked LAs are degraded only in the liver microsomes by dealkylation
and hydrolysis.
Systemic Effects
Any local anaesthetic injected or applied locally in ultimately absorbed and can
produce systemic effects depending on the conc. attained in the plasma and
tissues.
CNS
LAs are capable of producing a sequence of stimulation followed by depression.
They can cause drowsiness, confusion, lethargy and tremor. The tremor can
progress to convulsion. It can also cause respiratory depression.
CVS
The Cardiovascular effects are mainly from myocardial depression and
vasodilatation, which lead to hypotension. Reduction of myocardial contractility
may be from an inhibition of the Na + current in cardiac muscle. It can also cause
cardiac arrhythmias.
Methods of administration of LAs
1. Surface Anaesthesia; it is produced by topical applications of a surface
anaesthetics to mucous membrane and abrades skin, only the superficial
layer is anaesthetised. This is used on nose mouth, bronchial tree, cornea,
urinary tract
2. Infiltration anaesthesia; Dilute solution of LAs is infiltrated under the
skin in the area of operation to block sensory nerve endings. Onset of
action is almost immediate and duration is shorter than after nerve block.
3. Conduction block; The LAs is injected around nerve trunks so that the
area distal to injection is anaesthetized and paralysed.
Conduction block could be field block (injecting the LAs subcutaneously
in a manner that all nerves coming to a particular field are blocked) or
Nerve block (produced by injecting the LAs around the appropriate nerve
trunks or plexuses).
4. Spinal anaesthesia. The LAs is injected in the subarachnoid space
between L2-L3 and L3-L4. The primary site of action is the nerve root in
the cauda equina rather than the spinal cord. The lower abdomen and the
lower limbs are anaesthetised and paralysed.
Complication of spinal anaesthesia
i) respiratory paralysis
ii) hypotension
iii) headache
iv) cauda equina syndrome
v) septic meningitis
vi) nausea and vomiting
Contra-indications to spinal anaesthesia
i) hypotension & hypovolemia
ii) uncooperative or mentally ill patient
iii) infants and children
iv) vertebral abnormalities like kyphosis, lordosis
v) sepsis at injection site
5. Epidural anaesthesia: the LAs is injected in the dural spaces through
which nerve roots travel.
Epidural anaesthesia can be divided into three depending on the site of
injection as:
a. Thoracic
b. Lumbar
c. Caudal
