Local anesthetics work by reversibly blocking nerve conduction. They alter the nerve membrane potential and decrease nerve firing and depolarization rates. Local anesthetics are classified as esters, amides, or ketones. After injection, esters are quickly broken down while amides have longer half-lives and their toxicity is more likely if liver function is impaired. The onset and duration of local anesthetics are affected by tissue pH, concentration, and lipid solubility, with pH being most important. Adding epinephrine decreases systemic toxicity and increases duration by reducing absorption. Local anesthetic toxicity can cause CNS stimulation or depression as well as cardiovascular effects.

1. Prepared By Raheel Ahmad

2.  Local anesthetics (LA) are drugs that are used to prevent or relieve pain in
specific regions of the body without loss of consciousness. They act by reversibly
blocking nerve conduction.

3. Local Anesthesia works by:
 Altering the basic potential of the nerve membrane
 Altering the threshold or firing level
 Decreasing the rate of depolarization
 Prolonging the rate of repolarization

5.  LOCAL ANESTHETICS CALSIFICATION –
 Esters Cocaine, Procaine Chlore procaine ,Tetracaine . –
 Amids : Lidocaine Mepivacaine, Prilocaine Articaine Popivacaine, Etidocaine. –
 Ketons :Dyclon. –
 Quinoline: Centbucridine

6.  After injection into the area of nerve fibers, local anesthetics are absorbed into
blood.
 Ester-linked local anesthetics are quickly hydrolyzed by butyrylcholinesterase in
blood.
 Amide-linked local anesthetics can be widely distributed via circulation.
 Amide- linked local anesthetics are hydrolyzed by liver microsomal enzymes.
Thus, half life of these drugs are significantly longer and toxicity is more likely to
occur in patients with impaired liver function
 Absorption of local anesthetics is affected by following factors: – dosage, – site of
injection, – drug-tissue-binding and – Presence of vaso-constrictings.

7.  The onset and duration of action of local anesthetics are effected by several factors including :
 tissue pH
 nerve morphology
 Concentration
 pKa
 lipid solubility of the drug.
pH of the tissue and pKa are most important. At physiologic pH, these compounds are charged.
The ionized form interacts with the protein receptor of the Na+channel to inhibit its function and
achieve local anesthesia.
The pH may drop in infected sites, causing onset to be delayed or even prevented. Within limits,
higher concentration and greater lipid solubility improve onset somewhat.
Duration of action depends on the length of time the drug can stay near the nerve to block sodium
channels.

8.  Local anesthetics cause vasodilation, leading to rapid diffusion away from the site
of action and shorter duration when these drugs are administered alone.
 the vasoconstrictor epinephrine, the rate of local anesthetic absorption and
diffusion is decreased.
 This decrease systemic toxicity and increases the duration of action.
 Hepatic function does not affect the duration of action of local anesthesia,
 Some local anesthetics have other therapeutic uses (for example, lidocaineis an IV
antiarrhythmic)

9.  1. Topical Anesthesia
Anesthesia of mucous membranes of the nose, mouth and throat can be produced by
direct application of aqueous solutions of salts of many local anesthetics or by
suspension of the poorly soluble local anesthetics as tetracaine (2%) or lidocaine
(2%). Epinephrine, topically applied, has no significant local effect and does not
prolong the duration of action of local anesthetics applied to mucous membranes
because of poor penetration.
 2. Infiltration Anesthesia:
Infiltration anesthesia is the injection of local anesthetic directly into tissue without
taking into consideration the course of nerves. The local anesthetics used most
frequently for infiltration anesthesia are 1- lidocaine 2- procaine 3- bupivacaine
When used without epinephrine, greater amounts could be given

10.  3- Field Block Anesthesia:
Field block anesthesia is produced by subcutaneous injection of a solution of local
anesthetic in order to anesthetize the region distal to the injection.
 4- Nerve block:
Injection of a solution of a local anesthetic into or about individual peripheral
nerves or nerve plexuses

11.  1. pH influence
 Usually at range 7.6 – 8.9
 Decrease in pH shifts equilibrium toward the ionized form, delaying the onset
action.
 Lower pH, solution more acidic, gives slower onset of action
 2. Effect of inflammation on the activity of local anesthetics
 Inflammation increases the acidity of the medium
 Therefore, administration of local anesthetics at sites of inflammation increases
their ionization .
 This leads to lesser penetration into the nerves and, therefore, lesser activity

12.  3- Factors affecting absorption of local anesthetics into the systemic circulation
 Dosage (higher dose = greater probability of systemic absorption)
 Site of injection (injection at areas of large blood supply increase absorption)
 Presence of vasoconstricting drugs.

13.  4- Vasodilation
 Vasoconstrictor is a substance used to keep the anesthetic solution in place at a
longer period and prolongs the action of the drug
 vasoconstrictor delays the absorption which slows down the absorption into the
bloodstream
 Lower vasodilator activity of a local anesthetic leads to a slower absorption and
longer duration of action
 vasoconstrictor used the naturally hormone called epinephrine (adrenaline).
Epinephrine decreases vasodilator. Side effects of epinephrine
 Epinephrine circulates the heart, causes the heart beat stronger and faster, and
makes people feel nervous

14. FACTOR
ACTION
AFFECTED
DESCRIPTION
pKa Onset
Lower pKa = more rapid onset of action, more RN
molecules present to diffuse through nerve sheath, thus
onset time is decreased
Lipid solubility Anesthetic potency Increased lipid solubility = increased potency
Protein binding Duration
Increased protein binding allows anesthetic cations
(RNH+) to be more firmly attached to protein located at
receptor sites, thus duration of action is increased
Tissue diffusibility Onset Increased diffusibility = decreased time of onset
Vasodilator activity
Anesthetic potency and
duration
Greater vasodilator activity = increased blood flow to
region = rapid removal of anesthetic molecules from
injection site, thus decreased anesthetic potency and
decreased duration

15.  Adverse effects are usually caused by :
 high plasma concentrations of a local anesthetic drug that result from –
inadvertent intravascular injection,
 excessive dose or rate of injection
 delayed drug clearance
 administration into vascular tissue

16.  These effects occur due to systemic absorption of large doses due to
 : 1- accidental intravascular injection
 2- Injection of large doses
Central nervous system: --
 Stimulation of the CNS caused by inhibition of inhibitory neuronal activity, producing
 1- restlessness
 2- tremors that may proceed to convulsions. –
 At high blood concentrations, local anesthetics cause depression and even respiratory
failure
 Administering a 20% lipid emulsion infusion (lipid rescue therapy) is a valuable asse

17.  Peripheral nervous system: --- Local anesthetics affect transmission at the
neuromuscular junction producing muscle weakness and tremors.
 Smooth muscles: --- Depress contractions of intestine, vascular, and bronchial
smooth muscle.
 Allergic reaction: --- Ester-linked local anesthetics may cause allergic reactions in
a small population of patients due to their metabolism producing para amino
benzoic acid which is allergy

18.  Cardiovascular system: ---
 Decrease electrical excitability, conduction rate, and force of contraction in the
myocardium.
 Cause arteriolar dilation.
 Cocaine differs from the other local anesthetics: it blocks norepinephrine
reuptake, resulting in vasoconstriction and hypertension, even cardiac
arrhythmias

19.  Allergic shock:
 Patient reports of allergic reactions to local anesthetics are fairly common, but often
times reported “allergies” are actually side effects from epinephrine added to the local
anesthetic.
 Psychogenic reactions to injections may be misdiagnosed as allergic reactions and may
also mimic them with signs such as urticaria, edema, and bronchospasm.
 True allergy to an amide local anesthetic is exceedingly rare, whereas the ester
procaineis somewhat more allergenic.
 Allergy to one ester rules out use of another ester, because the allergenic component is
the metabolite para-aminobenzoic acid, produced by all esters.
 In contrast, allergy to one amide does not rule out the use of another amide.
 A patient may be allergic to other compounds in the local anesthetic, such as
preservatives in multidose vial

20.  Allergic shock:
 Esters are highly allergenic, their use should be avoided and restricted to special
cases after allergy test.
 a patient may in fact be allergic only to the bisulfite preservative used to stabilize
the vasoconstrictor.
 If the allergic reaction was not too serious, it may be worth trying again with
either mepivicaine or prilocaine without vasoconstrictor. Anesthetic manufactures
do not use preservatives in carpules that do not also contain vasoconstrictor

21.  Signs and symptoms of anesthetics allergic reaction
 The signs and symptoms of allergic reaction include: – generalized body rash or
skin redness – itching, urticaria (hives) – broncospasm (difficulty breathing) –
swelling of the throat – asthma – abdominal cramping – irregular heartbeat –
hypotension (low blood pressure) – swelling of the face and lips (angioneurotic
edema)

22. Anaphylactic shock
 Fortunately, the majority of allergic reactions to local anesthetics are fairly mild
 In a very serious anaphylactic reaction, the patient may experience serious
difficulty breathing due to closing down of the bronchioles in the lungs or swelling
in the throat area due to urticaria as well as seriously low blood pressure leading
to anaphylactic shock. This set of events, left untreated can lead to death
Management of anaphylactic shock
 Position the patient on his or her back with the feet elevated.
 Maintain an airway. If the patient is not breathing on his own, use rescue
breathing like you learned in CPR class.
 Check the carotid artery for heartbeat and use chest compressions if necessary

23.  The two drugs that you must have on hand to stabilize a patient in anaphylactic
shock are as follows: –
 Epinephrine (adrenalin) 1:1000 subcutaneous injection. It opens the bronchioles
allowing free breathing, increases the blood pressure counteracting shock and
evens out and intensifies the heart beat. Its effects are drastic, but short lived.
The standard dose is 1 mg given in three doses five minutes apart. –
 Benedryl (diphenhydramine) 25-50 mg injectable. This is an antihistamine and
can also be taken in pill form an hour before the procedure to help prevent serious
allergic reaction before it begins. Injectable diphenhydrimine which can be
administered either subcutaneously, or in the buccal fold if the dentist is more
comfortable with that rout

24.  Pregnant woman
 Local anesthesia are not teratogenic, and may administered to pregnancy patient
is usual clinical doses.
 Large dose of prilocaine are know to cause methemoglobinemia which could cause
maternal & fetal hypoxia.
 Local vasoconstriction – Delay uptake from the site of injection – Increase the
effectiveness & duration There is no specific contraindication to these
vasoconstrictors in a pregnant patient although it is prudent to use minimal
effective dose.

25.  Pregnant woman
 Lidocaine + vasoconstrictor: most common local anesthetic used in dentistry
extensively used in pregnancy with no proven ill effects• accidental intravascular
injections of lidocaine pass through the placenta but the concentrations are too
low to harm fetus•
 Drug classes: B: lidocaine, prilocaine, etidocaine C: mepivacaine, bupivacaine Not
yet assigned: Procaine• The need for careful Hx taking & for aspiration & slow
injected technique is obvious

26.  Before administering local anesthetic to a child, the maximum dose based on
weight should be calculated to prevent accidental overdose.
 There are no significant differences in response to local anesthetics between
younger and older adults.
 It is prudent to stay well below maximum recommended doses in elderly patients
who often have some compromise in liver function. Because some degree of
cardiovascular compromise may be expected in elderly patients, reducing the dose
of epinephrine may be prudent.
 Local anesthetics are safe for patients who are susceptible to MH