local anesthetics agents

Local Anesthetia

Iyad M.Abou Rabii

Qassim University – College of Dentistry

3rd year - January 2010

Lecture Objective

– Define local anesthesia.

– Classify local anesthetics into the two major categories according to their chemical structure.

– Confer the pharmacokinetics of local anesthetics.

– Describe the anatomical variations and pulpal conditions as complicating factors for local anesthetics.

– Understand the clinical options of different delivery methods of local anesthetics.

– Explain factors Affect the Reaction of Local Anesthetics

– List undesired systemic effects of local anaesthetics and vasoconstrictors

– Describe local anesthesia allergic (anaphylactic) shock etiology and management

– Description of special medical cases in local anesthesia (child, pregnant woman , geriatric, handicapped patient)

– List Local anesthetics interaction with other drugs.

Local anaesthetics

Definition and function

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.

Cell Membrane Receptors

Membrane potential and neurotransmission:

Neuron transmits information mainly by two mechanisms:

– chemical

– and electrical signals.

Information within a neuron is mainly transmitted by electrical signals.

Electrical signals are propagated by the mechanism called action potential.

Mechanism

How Local Anesthetics Work

Altering the basic potential of the nerve membrane

Altering the threshold or firing levelDecrasing the rate of depolarization Prolonging the rate of repolarization

LOCAL ANESTHETICS CALSIFICATION

– Esters : Cocaine, Procaine , Chlore

procaine ,Tetracaine .

– Amids : Lidocaine , Mepivacaine, Prilocaine , Articaine ,

Popivacaine, Etidocaine.

– Ketons :Dyclon.

– Quinoline: Centbucridine .

Differences of Esters and Amides

Two classes of local anesthetics are amino amides and amino esters.

Amides: Esters:

--Amide link b/t intermediate --Ester link b/t intermediate chain and chain and aromatic ring aromatic ring

--Metabolized in liver and very --Metabolized in plasma --Cause allergic reactions

Pharmacokinetics

Following injection into the area of nerve fibers to be blocked, 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 lifes of these drugs are significantly longer and toxicity is more likely to occur in patients with impaired liver function.

Pharmacokinetics

Absorption of local anesthetics is affected by following factors:

– dosage,

– site of injection,

– drug-tissue-binding and

– Presence of vaso-constricting drugs

Vasoconstrictors

Application of local anaesthesia

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.


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

Factors Affect the Reaction of Local Anesthetics

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

Effect of inflammation on the activity of local anaesthetics

Inflammation increases the acidity of the medium

Therefore, administration of local anaesthetics at sites of inflammation increases their ionization .

This leads to lesser penetration into the nerves and, therefore, lesser activity.

Factors affecting absorption of local anaesthetics 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.

Factors Affect the Reaction of Local Anesthetics (cont.)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.

Undesired systemic effects of local anesthetics

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,

– or administration into vascular tissue.

Undesired systemic effects of local anesthetics

Undesired systemic effects of local anesthetics:

Occur due to systemic absorption of large doses due to :

1- accidental intravascular injection

2- Injection of large doses

I- 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..

Undesired effects of local anesthetics

II- Peripheral nervous system:

--- Local anesthetics affect transmission at the neuromuscular junction producing muscle weakness and tremors.

III- Smooth muscles:

--- Depress contractions of intestine, vascular, and bronchial smooth muscle.

IV- 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 allergic .

Undesired effects of local anesthetics

V- 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.

Local Anesthesia Allergic shock

Esters are highly allergenic, their use should be avoided and restricted to special cases after allergy test.

There has never been a true, documented allergic reaction to an amine anesthetic.

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.

Testing for anesthetic allergy using skin test

T.R.U.E. Test®

This is a patch test that applies 23 allergens to the skin contained in 12 polyester patches. One of the patches contains a mixture of several anesthetics and is used to test for allergy to local anesthetics in general. The mixture used includes two ester based anesthetics and one amine based anesthetic. This mixture of anesthetics is called the "Caine Mix"

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)

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 : 1

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. Thanks for Dr. Yasser

Check the carotid artery for heartbeat and use chest compressions if necessary.


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 mgm 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 route.


The following drugs are of little use to the dentist during the initial stages of the emergency since they are generally used by EMS personnel

– Aminophylline This drug opens blocked breathing passages.

– Solu-cortef IV injection. This drug is a corticosteroid and reduces the generalized allergic inflammatory reactions on a longer term basis. It will not act rapidly enough to reverse anaphylaxis immediately, but is more of a long term remedy.

– Wyamine injection. This drug is used to counteract hypotension (low blood pressure and shock) on a prolonged basis.

Choose the right Dose

Preparations

Minimum Toxic Dose

Maximum Dose

Dosage guidelines

Lower concentrations of local anesthetics are typically used for infiltration anesthesia.

Variation in local anesthetic dose is dependent on the procedure, the degree of anesthesia required, and individual patient circumstances.

Reduced dosage is indicated in debilitated or acutely ill patients; in very young children or geriatric patients; and in patients with liver disease, arteriosclerosis, or occlusive arterial disease.

LA Management of Special Ptient

Children should have a comfortable experience when going to the dentist. Local anesthetics are an important tool for

the control of pain and discomfort during dental treatment

Children

What local anesthetic

All local anesthetics have a low margin of safety between the effective dose and the toxic dose. The lethal dose for many local anesthetics is only 3 times that of the effective dose.

Deaths following local anesthetic administration are almost always a result of overdosage.

The maximum safe dose of lidocaine for a child is 4.5 mg/kg per dental appointment.

What local anesthetic

Bupivicaine (Marcaine) is an amide local anesthetic with a high toxic potential, and should not be used in children. The duration of anesthesia with bupivicaine can be as long as 24 hours.

Lidocaine is less toxic than many other local anesthetics, because its interactions with the cardiac sodium channel are “fast in – fast out,” whereas a local anesthetic such as bupivicaine is "fast in – slow out.”

So the best LA to be used with children is

Lidocaine

What Technique

Local infiltration of anesthesia is sufficient for all dental treatment procedures in 90% of cases even in the mandible.

Nerve bloc is not preferable, just in special cases.

Local infiltration is less painful when done correctly

Handicapped Patient

Several issues arise concerning the use of local anesthesia with this population. One of these is lip biting

– Consideration should be given to choosing a short-acting local anesthetic to reduce the possibilityof post-operative trauma from lip biting.

– Another choice would be to avoid mandibular blocks and utilize infiltration, periodontal ligament

A second issue with local anesthesia is the inability to determine from a non-communicative patient when an acceptable level of anesthesia has been obtained.

– When in doubt second injections and alternative routes (e.g., buccal, mylohyoid, intraligamentary)

Handicapped Patient

An unresolved issue in treating these patients is that severely retarded patients have a higher pain threshold than the general population.

Some clinicians therfore choose not to use local anesthetic when the procedures involve minor restorative needs (e.g.,body pits or minor occlusal decay).

These patients are difficult to control. Injecting such a patient can be extremely difficult and may pose a significant danger to the patient and the staff.

One must choose a shorter needle and/or a larger gauge needle which is less likely to be bent or broken.

However it is better to use general anesthesia with Handicapped patients.

Patients receiving anticoagulation or suffering from bleeding disorders

oral procedures must be done at the beginning of the day because this allows more time to deal with immediate re-bleeding problems.

Also the procedures must be performed early in the week, allowing delayed re-bleeding episodes, usually occurring after 24-48 h, to be dealt with during the working weekdays.

Local anesthetic containing a vasoconstrictor should be administered by infiltration or by intraligamentary injection wherever practical.

Regional nerve blocks should be avoided when possible.

Local vasoconstriction may be encouraged by infiltrating a small amount of local anesthetic containing adrenaline (epinephrine) close to the site of surgery.

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.

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

For Information :

Pregnancy drug Clases

Medications are grouped into 1 of 5 categories based on the potential for producing birth defects. The categories are A, B, C, D and X. Generally speaking, drugs that fall into either class A or B are considered safe and are routinely used. There may be exceptions. Category A: Controlled studies in pregnant women fail to demonstrate a risk to the fetus in the first trimester with no evidence of risk in later trimesters. The possibility of harm appears remote.Category B: Presumed safety based on animal studies, with no controlled studies in pregnant women, or animal studies have shown an adverse effect that was not confirmed in controlled studies in women in the first trimester and there is no evidence of a risk in later trimesters.Category C: Studies in women and animals are not available or studies in animals have revealed adverse effects on the fetus and there are no controlled studies in women. Drugs should be given only if the potential benefits justify the potential risk to the fetus.Category D: There is positive evidence of human fetal risk (unsafe), however in some cases such as a life-threatening illness the potential risk may be justified if there are no other alternatives.Category X: Highly unsafe: risk of use outweighs any potential benefit. Drugs in this category are contraindicated in women who are or may become pregnant.

GERIATRIC PATIENT

When choosing an anesthetic, we are largely concerned with the effect of the anesthetic agent upon the patient's cardiovascular and respiratory systems.

increased tissue sensitivity to drugs acting on the CNS

Decreased hepatic size and blood flow may reduce hepatic metabolism of drugs

hypertension is common and can reduce renal function

Same prevention procedures used with children

LIVER DISORDERS

Advanced liver diseases include:

Liver cirrhosis - Jaundice

Potential complications:

1. Impaired drug detoxication e.g. sedative, analgesics, general anesthesia.

2. Bleeding disorders ( decrease clotting factors, excess fibrinolysis, impaired vitamin K absorption).

3. Transmission of viral hepatitis.

Management

Avoid LA metabolized in liver: Amides (Lidocaine, Mepicaine), esters should be used

Drug-Drug Interaction

Local anesthetics and vasoconstrictor may interact with other prescribed drugs.

list of administrated drugs to the patient can play a role in the local anesthetic choice.

References

Calatayud Jesús and González Ángel. History of the Development and Evolution of Local Anesthesia Since the Coca Leaf. © 2003 American Society of Anesthesiologists Volume 98(6) June 2003 pp 1503-1508.

Peter C. Meltzer, Shanghao Liu, Heather S. Blanchette, Paul Blundell, Bertha K. Madras. Design and Synthesis of an Irreversible Dopamine-Sparing Cocaine Antagonist. @ Bioorganic & Medicinal Chemistry Volume 10, Issue 11 , November 2002, Pages 3583-3591

Shigeki Isomura, Timothy Z. Hoffman, Peter Wirsching, and Kim D. Janda. Synthesis, Properties, and Reactivity of Cocaine Benzoylthio Ester Possessing the Cocaine Absolute Configuration. J. AM. CHEM. SOC. 2002, Issue 124, p.3661-3668

Mazoit, Jean-Xavier; Dalens, Bernard J. Pharmacokinetics of local anesthetics in infants and children. Clinical Pharmacokinetics (2004), 43(1), 17-32.

Alejandro A. Nava-Ocampo and Angelica M. Bello-Ramirez. Lipophilicity Affects the Pharmacokinetics and Toxicity of Local Anaesthetic Agents Administered by Caudal Block. Clinical and Experimental Pharmacology and Physiology (2004) 31, 116-118.

Don R Revis, Jr. Local Anesthetics. October 14,2004: (Medline)

http://www.emedicine.com/ent/topic20.htm

http://www.sciencedirect.com/science?_ob=JournalURL&_cdi=5220&_auth=y&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ad641afa273735df4acb139fabed74b6

http://www.sciencedirect.com/science?_ob=IssueURL&_tockey=

http://www.emedicine.com/ent/topic20.htm

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