LOCAC ANAESTHETICS

LOCAL ANAESTHETICS
Local anaesthetics (LAs) are drugs which cause
reversible loss of sensory perception, especially of
pain, in a restricted area of the body where they are
applied
They block generation and conduction of nerve
impulse at any part of the neurones with which they
come in contact, without causing any structural
damage
Local Anaesthetic Properties
Activity of these drugs maybe affected by
Percent of ionization at Physiological Ph
Lipid solubility
Affinity for protein binding
Vasodilatation effect
PROPERTY CONT..
Lipid solubility
This is the most significant property of local
anaesthetics molecules in determining the drug potency
Lipophilic molecules penetrate the nerve cell membrane
and become intracellular, resulting into more blockades’
 E.g Bupivacaine is more lipid soluble and thus more potent
than lidocaine
PROPERTY CONT..
Ionozation
These drugs exists in ionized and non ionized forms
which is determined by Ph of the medium
The non ionized form is the portion that is capable of
diffusing across nerve membranes and blocking sodium
channel
 The non ionized aslo has a fast onset of action due to rapid
diffusion.
 When equilibrium pH of a specific local anaesthetic
approaches the physiological pH of the tissiue (ie 7.35-7.45)
the more rapid onset of action
PROPERTY CONT..
A decrease in pH shifts the equilibrium towards the
ionized form and thus delays onset of action
This explains why local anesthetics have delayed onset
of action and less effective in inflammation as
inflammation creates more acidic environments
Addition of Na bicarbonate to local anesthetic may
reverse this, however; over alkalization can cause local
anesthetic agent to precipitate
Local Anaesthetic Properties
Protein binding
Those with high binding capacity tend to have incraesed duration of
action such as bupivacaine and etidocaine unlike those which are less
protein bound such as pracaine
α -acid glycoprotein and albumin are the main sites for local
1

anaesthetic binding
Vasodilatation
Except cocaine most have biphasic effect on vascular smooth muscles
 At low dosage the cause vasoconstrictions
 At high dosage they cause vasodilatation via direct relaxation of arterioles
smooth muscles fibers
 The more vasodilatory effect it has the more it gets washed away and thus
the short duration of action
General mechanism of actions
They reversibly binds to voltage gated sodium channel
once they reach the neurones; blocking Na+
movement through the channel and thus blocking the
action potential and neural conduction
 Finally, local depolarization fails to reach the
threshold potential and conduction block ensues
General mechanism of action
Na+ channel receptors can be
found in 3 forms
RESTING,ACTIVATED,
INACTIVATED
 LA receptor is located within
the channel in its intracellular
half.
Cationic form(BH)+ of the LA
which primarily binds to the
receptor.
Note atfer intering cell they
dissociates .
The orderof LA ffinity
activated, inactivated and
finally resting .
Mechanism of differential blockade
Fasculi that are located near the surface of the nerve
(mantle bundles) are reached by local anaesthetics
and blocked first and completely
Fasculi found closer to the center of the nerve i.e core
bundles are exposed to less anaesthetic solution and
thus delayed response
Thus small unmyelinated C fibers (pain) and small
myelinated Aδ fibers( pain and touch) are blocked
before larger myelinated Aγ, Aβ and Aα
fibers(postural, touch ,pressure and motor signals)
Classification
Classification cont..
Amides Esters
Produce more intense and longer Short duration of action short
lasting anaesthesia duration
• Bind to α1 acid glycoprotein in  less intense analgesia
plasma
 Higher risk of hypersensitivity
• Not hydrolysed by plasma esterases
 The ester-linked LAs are rarely
• Rarely cause hypersensitivity
reactions; used for infiltration or nerve
no cross sensitivity with ester LAs
block, but are still used topically
Lidocaine,
on mucous membranes.
Cocaine,
 bupivacaine,
dibucaine, procaine,
prilocaine, chloroprocaine,
 ropivacaine. Tetracaine, benzocaine.
Local Anaesthesia systemic Toxicity(LAST)
Central nervous system
Central toxicity results from high levels of local anaesthetic agent within
the brain.
 This may be due to direct spread from subarachnoid injection or by excessive
systemic absorption.
 Transfer across the blood–brain barrier is influenced by lipid solubility and

ionization.
The toxic CNS effects follows..
 Numbness and paraesthesia of tongue, mouth and lips

 Metallic taste

 Light headiness

 Tinnitus

 Slurred speech

 Muscle twitching

 Shivering

 tremors
Local Anaesthesia systemic Toxicity(LAST)
Grand mal convulsions
 Coma

Apnoea
Apnoea and convulsions result in hypoxia,
hypercapnia and metabolic acidosis.
 The acidosis increases the proportion of ionised local
anaesthetic agent.
Toxicity results from the presence of ionised drug
within the cell blocking the ion channel.
 Acidosis effectively reduces the proportion of
diffusible drug within the cells, and slows clearance
SYSTEMIC EFFECTS
Cardiovascular system
Most local anaesthetic agents (except cocaine) relax
vascular smooth muscle, causing vasodilatation.
Direct cardiovascular toxicity is caused by the
membrane-stabilising activity of the drugs on
myocardial muscle, which is a feature of blockade of
voltage-gated fast sodium channels.
SYSTEMIC EFFECTS
Cardiac toxicity may result in any of the
followingeffects:
 Prolongation of PR interval
 Supraventricular tachycardia
 Decreased automaticity
 Widening of QRS complex
Ventricular ectopic beats
 Prolongation of ST interval
 T-wave changes
SYSTEMIC EFFECTS
SYSTEMIC

EFFECTS
Respiratory system
The respiratory effects of local anaesthetic agents are
due to combination of peripheral neuronal blockade and
systemic toxicity.
 Apnoea with systemic toxicity affecting the respiratory centre
 Bronchodilatation secondary to relaxation of bronchial
smooth muscle
Other effects
Local anaesthetic drugs have a weak neuromuscular
blocking action.
 Amides block plasma cholinesterase
They may cause anaphlatic reaction due to preservatives
METABOLISM
Ester local anaesthetics are rapidly metabolised by
plasmacholinesterase, and systemic toxicity is rarely
a problem.
 Amide local anaesthetics are metabolised by the liver,
Hepatic failure must be very severe for their metabolism
to be affected.
THE ISSUES
Glucose
OF ADDITIVES
Standard solutions of local anaesthetic agents are
slightly hypobaric at body temperature and pH.
 Tend to move upwards in the cerebrospinal fluid away
from the gravitational pull.
Glucose is added to these local anesthetics to make
hyperbalic
 Eg hyperbalic lignocaine nad bupivacaine
Epinephrine
Epinephrine is added to local anaesthetic solutions to
reduce vascularity of the area by direct vasoconstriction.
This in turn reduces the systemic uptake of the drug
THE ISSUES OF ADDITIVES
Hyaluronidase
This facilitates facilitate the spread through connective
tissues following subcutaneous or intramuscular injection.
It is supplied as white fluffy powder

 pH manipulation
Alkalization of solutions by addition of bicarbonate
increases tissue pH. This results in a higher proportion of
non-ionised drug, which diffuses into the neurone more
rapidly.
Amide-linked agents

Bupivacaine
Bupivacaine is a long-acting local anaesthetic agent with
a slow onset of action.
Blockade of a large peripheral nerve such as the sciatic
nerve may take 60 minutes, depending on the approach
 Intrathecal injection in contrast produces an acceptable
block within a few minutes
prone to causing myocardial depression.
 Reversal may be slow due to high Pk and high affinity to
cardiac proteins
To avoid systemic effect, this drug should be avoided
in
Avoid bupivacaine in IVRA
Avoid 0.75% bupivacaine in obstetric practices
Limit dose to 2mg/kg .
Metabolism
 N-dealkylation to pipecolylxylidine (N-
desbutylbupivacaine).Hydroxybupivacaine is also
produced.
 The metabolites areexcreted in the urine.
Lidocaine (lignocaine)
Lidocaine is primarily classified as a local anaesthetic
agent but is also a Class IB antiarrhythmic
Has rapid onset of action and intermidiate effect up to
45 min.
May be combined with bupivacaine to balance the onset
of action and duration of action between these two
drugs
Metabolism
N-dealykalation followed by hydrolysis to form
ethylgylcine and xylidide which are excreted by the
kidneys.
Prilocaine
This is more related to lidocaine in terms of
pharmacological effects
They have the same Pka- 7.9
Can lead to Methaemoglobinaemia which can can lead to
cynosis.
Ester-linked agents

Cocaine
Cocaine is a naturally occurring ester derived from
benzoic acid.
Can be extracted from the leaves of Erythroxylumcoca.
Available in solution and paste formulation in conc
of 1% and 10%
It is mainly used for topical anaesthesia and to reduce
bleeding during nasal surgery
Indication-The only indication for cocaine is in ocular
anaesthesia
Ester-linked agents

Effects in the CNS

Cocaine initially blocks the inhibitory pathways resulting.
 euphoria
 hyperthermia
 altered vision and hearing, nausea
 eventually convulsions.
Higher levels of cocaine also block the excitatory
pathways, resulting in central nervous depression leading
to sedation and unconsciousness, with respiratory
depression.
Ester-linked agents

Amethocaine
Amethocaine (tetracaine) is an ester local anaesthetic
agent used for topical anaesthesia.
 It is available as a gel (4%) for local anaesthesia of the
skin before intravascular cannulation.
INDICATIONS OF LOCAL ANAESTHETICS
1. Surface anaesthesia
It is produced by topical application of a surface
anaesthetic to mucous membranes and abraded skin.
2. Infiltration anaesthesia
 Dilute solution of LA is infiltrated under the skin in
the area of operation
blocks sensory nerve endings
. Onset of action is almost immediate and duration is
shorter than that after nerve block,
INDICATIONS OF LOCAL ANAESTHETICS
3. Conduction block
The LA is injected around nerve trunks so that the area
distal to injection is anaesthetised and paralysed.
This can be
 Nerve block- -a specific nerve is blocked
 Field block--all nervescoming to a particular field are blocked.

4. Spinal anaesthesia

5. epidural anaesthesia
6. intravenous regional anaesthesia
References