Local
anesthesia
stage
rd
3
Pharmacology
Group of drugs which are block impulse conduction reversibly along nerve axons when applied
locally in an appropriate concentration, this can be utilized clinically to loss sensation in a
circumscribed or specific area of body
Local anesthetics can be classified according to their chemical structure into esters and amides,
each consists of a lipophilic aromatic ring connected to hydrophilic end by an ester or amide (the
nature of the intermediate chain defined the type)
Examples:
Esters: - Cocaine, Procaine, Tetracaine and Benzocaine
Amides: - Lidocaine, Prilocaine, Bupivacaine and Mepivacaine
Important practical differences between these two groups of LA agents
1-Esters are relatively unstable in solution (Breakdown in ampule by heat or sun), while amides are
relatively stable in solution
2-Esters are rapidly hydrolyzed in the body by plasma cholinesterase while amides are slowly
metabolized by hepatic amidase
3- One of the main breakdown product of esters is para-amino benzoic acid (PABA) which is
associated with allergic phenomena and hypersensitivity reaction while hypersensitivity reaction
to amides are extremely rare
4- Onset of esters action is slow while for amides is moderate to fast
5- Esters PH is higher than 7.4(8.5-8.9), while for amides close to 7.4 (7.6- 8.1)
6- Systemic toxicity of esters is lower than that with amides
Mechanism of action
Blocking of sodium ion channels, this will lead to increase in the threshold of excitability result in:
1-Prevent the initiation and conduction of nerve impulses
2-Blocks the conduction by sensory, autonomic and motor nerve endings
3- The fibers in the nerve trunks are affected in order depend on diameter size, the smallest
(autonomic) fibers affected first, followed by sensory fibers and lastly the motor fibers Local
anesthetic drugs appear to compete with calcium ions at the sites affect sodium fluxes and
prevent binding of calcium to the nerve membrane phospholipidClinically, there is loss of pain
sensation first followed by loss of heat and cold sensation (temperature) then loss of pressure
sensation (touch) and lastly motor fibers (movement) this evident when an area seems fully
anesthetized for surgery, but the patient still feels the pressure of the surgeon's fingers
Pharmacokinetic
1-Distribution depend on diffusion in the tissue and blood flow and the type of drug
2- Local injection act within 5 minutes and may last up to 1.5 hours and this duration can be
doubled by the use of vasoconstrictor drug in combination with the local anesthetic
3- Absorption from the site of application will terminate the action of the LA, most LA produce
some degree of vasodilatation and they may be rapidly absorbed after local injection
Prolongation of the action of local anesthetics
This can be achieved by giving the LA with vasoconstrictor drug usually Adrenaline that cause
vasoconstriction at the site of injection and will delay the absorption of anesthetic and prolonged
its duration of action ; this combination should not be applied to the end organs such as fingers,
nose and toes ,because may lead to sever vasoconstriction and cause gangrene
Another adverse effects of adrenaline, it may cause elevate blood pressure and cardiac
dysrhythmias; therefor; this combination should be avoided in patients with heart diseases and
hypertension
Felypressin is an alternative vasoconstrictor to adrenaline, it is synthetic analogue of vasopressin,
cause less elevate of blood pressure and less tachycardia
Methods of local anesthetic application:
1- Surface anesthesia (topical anesthesia)
As solution, cream, ointment, spray, and gel applied locally to mucous membranes, eyes, nose,
mouth, and ear, like Lidocaine gel 2 % and Prilocaine
2- Infiltration anesthesia, to paralysis sensory nerve ending and small cutenous nerves, in this
case the anesthetic is injected into the tissue (provide anesthesia for minor surgical procedures),
commonly used amides LA, the site of action is at unmyelinated nerve fibers and onset of action is
immediate
3- Nerve block; can anesthetized a region as brachial plexus, paravertebral nerves or individual
nerves as ulnar, sciatic or pudendal block
4- Intravenous reginal anesthesia (IVRA):
A cuff applied to the arm and inflated above arterial pressure and the vein filled with local
anesthesia e.g. 0.5% of lidocaine; the arm is anesthetized in 6-8 minutes and the effect last up to
40 minutes if the cuff remain inflated, Bupivacaine and Etidocaine should never be used for
IVRA(they are significantly protein binding and once the tourniquet is released there is a risk of
cardiotoxicity
5- Extradural block; used in thoracic, lumbar, and sacral region; the drug is injected in the
extradural space and acts on the nerve root, used mainly in obstetrics
6- Spinal anesthesia; the drug is injected intrathecal and the patient is tilted, hypotension occurs
due to sympathetic block and headache due to CSF leakage (injection directly into the CSF,
subarachnoid space produce spinal anesthesia
Side effects
1-Exessive systemic absorption causes nervousness, tremor, anxiety and even convulsion,
respiratory depression may occur.
2- Myocardial depression, conduction block and hypotension
3- Local allergic reaction as skin rash
Individual local anesthetics
1-Lidocaine (Xylocaine);
it is an amide has a half-life of about 1.5 hours, it is the drug of choice for surface anesthesia as
well as for injection ,it is with low toxicity ,it is also useful in the treatment of cardiac dysrhythmias
especially ventricular arrhythmias (classified as class 1B),sodium channel blockade with shorting
the refractory period)
2- Prilocaine
It is similar to lidocaine, but it is less toxic and can be mixed with lidocaine to form an emulsion
that penetrate skin and used to dermal anesthesia
3- Bupivacaine
It is long acting and used for peripheral nerve block, including epidural and spinal block
4- Cocaine
Is used as a surface anesthetic as 4% solution, it has many adverse effects when injected, cocaine
blocks the uptake of catecholamines (similar to tricyclic antidepressant) this can cause
vasoconstriction; while all other local anesthetics don’t have this action ; cocaine in addition to
local anesthetic effect has direct central effects as it causes euphoria and excitement and it can
cause dependence
5- Procaine has short duration of action and it is less used
6- Tetracaine, useful in topical application and it is rapidly absorbed, should be avoided in damage
skin and useful in ophthalmology
7- Mepivacaine ; used in dentistry with or without adrenalin