Local Anesthetics

Dr. maged bin hariz

• Definition
 A local anesthetic (LA) is a drag that induces a
reversible loss of sensation in a localized area of the
body without inducing loss of consciousness or sleep
• Chemistry:
 Are weak bases formed of lipophilic group connected
to ionizable hydrophilic group by an intermediate chain
which may be amide or ester
 Classification
I. Esters
 Rapidly hydrolyzed by plasma
pseudocholine esterases
 Short duration of action.
 less liable to systemic toxicity.
 Duration of action prolonged in
genetic enzyme deficiency
 More liable to allergy
 Members: Cocaine, procaine,
tetracaine, benzocaine
II. Amides
 redistributed & metabolized by liver.
 Long duration of action.
 more liable to systemic toxicity
 Duration of action prolonged in liver
disease& reduced hepatic blood flow
(e.g. heart failure).
 Members : Lidocaine,, bupivacaine,
mepivacaine
 Mechanism of Action of LA
• LA bind to receptors on inner surface of Na channel in
nerve membranes resulting in their blockade → inhibition
of generation & propagation of action potential→↓ nerve
conduction
 Absorption
• The rate and extent of absorption to and from
nerves are important in determining onset and
duration of action and also the potential for
systemic adverse effects.
• This rate is correlated with the relative lipid
solubility of the uncharged form and is
influenced by the dose and the drug's
physicochemical properties, as well as by
tissue blood flow and drug binding .
 LAs are weak bases (pKa between 7.7 and 9) .
 In order to increase their solubility and stability they are
prepared as acid salts (e.g. lidocaine HCI).
 The local anesthetic exists in 2 forms in equilibrium
according to its pKa & to the extracellular pH :
 1. Ionized form 2. Unionized form.
 Only the unionized form can cross the nerve membrane.
 Once inside nerve cell, the amount that crossed will again
re-equilibrate into unionized & ionized forms according to
the intracellular pH.
 The intracellular ionized form is the active form that blocks
Na~ channel.
 Reduced pH , as in inflamed tissues, increases the
prevalence of the cationic form , which reduces diffusion
into nerves and thereby reduces local anesthetic
effectiveness.
 Adjuvants of local anesthetics

• Vasoconstricotors e.g. adrenaline:

• prolongs duration of action and ↓systemic toxicity.
 Vasoconstrictors are added to LA (except cocaine) to reduce
blood flow and reduce absorption and thus prolongs the
duration of the anesthetic and ↓systemic toxicity.

• Sodium bicarbonate:
 All local anesthetics are weak bases. Adding NaHC03 to
LA solution → ↓ extracellular acidity →↑extracellular
unionized form (↑ lipid solubility )→ ↑LA penetration of
the anesthetic into the nerve sheath → ↑activity (rapid
onset).
 Uses & Administration
1. Surface (topical) anesthesia (for minor surgeries):
 • Applied to skin &mucous membranes of nose, mouth &cornea as a
solution, jelly or cream.
 Treatment of itching caused by insect bites or irritant condition.
 To relieve pain caused by oral, laryngeal, or rectal disorders e.g. piles.
 Corneal anesthesia in ophthalmic surgery.
2. Infiltration (for minor surgery):
 Injected sc &in submucosal tissues to reach nerve branches & terminals.
 Used for minor surgical procedures e.g. dental procedures.
 Epinephrine may be added to prolong the duration of action.
3. Nerve block (for dentistry &surgery):
 Injected close to nerve trunks proximal to the intended area of anesthesia
(e.g. dental nerves - brachial plexus).
4. IV regional anesthesia:
 A double cuff is applied to the arm & inflated above arterial BP & the LA is
injected IV after elevation of arm to drain the venous system.
5. Spinal anesthesia:
 Injected in subarachnoid space below L2(lumber vertebra) acts on spinal
cord.
 Used for surgery of abdomen, pelvis & lower limb when general
anesthesia is contraindicated.
• Side effects:
 Headache (due to CSF leakage & traction on sensitive structures, avoided
by use of pencil point needles).
 Hypotension (shock) → sympathetic nerve block.
 sometimes respiratory paralysis.
 Infection.( Septic meningitis)
6. Epidural anesthesia:
 Injected outside the dura, blocks spinal roots.
 Same indications as spinal anesthesia with ↓risk of side effects.
 Commonly used in obstetrics for painless labor.
 Adverse Effects &Toxicity
 Over dose or accidental iv injection→ ↑ systemic absorption
 CNS:
• Stimulation → restlessness, tremors and convulsions.(Low
concentration )
• Depression → respiratory failure → death (High concentration)
 CVS :
• Heart: →↓heart rate→ cardiac arrest.
• Blood Vessels: vasodilatation→↓BP
 Bupivacaine is extremely cardiotoxic in high doses .

 Neurotoxicity: due to the direct local effect of high concentration of

LA injected close to nerve trunks or spinal cord.
 Allergy: with esters that are derivatives of PABA e.g. procaine.