SOURCES Contemporary_Oral_and_Maxillofacial _ Surgery_4th_Ed_By_Peterson. Peterson's Principles of Oral and Maxillofacial Surgery 2nd Ed 2004. Oral Surgery. Hand Book Local Anasthesia.

LOCAL ANEASTHESIA

Definition of local anesthesia L.A. defined as a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve ending or an inhibition of the conduction process in peripheral nerves.

Methods of inducing L.A. In the “old days” the following were used for anesthesia. Alcohol Drugs Ice for numbing Blow to the head Strangulation

Methods of inducing L.A. Mechanical trauma Low temperature Anoxia Chemical irritation Neurolytic agents like alcohol Chemical agents such as L.A.

Properties of ideal L.A. Onset of anesthesia should be short while duration and effect of anesthesia should be long and powerful L.A should not irritate tissues L.A should not cause permanent damage to nerves L.A should be effective even with lower doses L.A should has lower systemic adverse effects L.A should not be allergic

Properties of ideal L.A L.A can be sterilized easily L.A should be soluable within water L.A should be cheap L.A should be stabile L.A should not get interaction with vasoconstrictors

Neurophysiology

Electrochemistry of nerve conduction Resting state Depolarization Re polarization

Mode of action of L.A. Altering the basic resting potential Altering the threshold potential(firing level) Decreasing the rate of depolarization Prolonging the rate of repolarization

What functions are lost with local anesthetics? Answer Pain perception Temperature Touch sensation Proprioception (reception of information about body position movements by the sensory systems ) Skeletal muscle tone

Factor affecting the local anesthetic action 1- PH value. Acidification of tissue decrease LA effectiveness Inadequate anesthesia result when local anesthetics are injected in to inflamed or infected areas since the inflammatory process produce acidic products. 2- Lipid solubility .↑ lipid solubility ↑ local anesthetic effect. 3- Protein binding . ↑ protein binding ↑LA duration . 4- Non nervous tissue diffusibility . 5-↑ Vasodilator activity ↓ LA solution activity.

Pharmacokinetic of local anesthetics Administration. Distribution. Metabolism. Excretion.

Induction of L.A. Recovery of L.A. 1-Diffusion 2-Blocking process Recovery of L.A. note all LA readily cross the blood brain barrier & also readily cross the placenta & enter the circulatory system of developing fetus.

Administration Oral rout Topical rout Injection

Distribution The blood level of L.A. influenced by Rate at which the drug is absorbed into CVS Rate of distribution from vascular component into the tissue Elimination by excretion

One half life =50% reduction Two half life=75% reduction Continue The rate at which the drug is removed from the blood mentioned as half life One half life =50% reduction Two half life=75% reduction Three half life=87.5 reduction Four half life=94% reduction Five half life=97% reduction Six half life= 98% reduction

Metabolism Metabolism of L.A is important because the overall toxicity of the drug depend on the rate of absorption of the drug into the blood stream and its rate of metabolism and excretion. Esters→ Hydrolysis in Plasma Amides→ Liver

Excretion Kidneys are the primary excretory organ for both local anesthetic drug and its metabolite.

Summary Clinical Pharmacology The potency of Local Anesthetics, their onset and duration of action are primary determined by physicochemical properties of various agents and their inherent vasodilator activity of same local anesthetics. Lipid solubility is the primary determinant of anaesthetic potency. Protein binding influences the duration of action. (acidity constant) of Local anaesthetics determines the onset of action. The addition of vasoconstrictors, such as epinephrine or phenylephrine can prolong duration of action of local anaesthetics, decrease their absorption (and the peak plasma level) and enhance the blockade.

Chemistry Three structural domains 1) Aromatic or Lipophilic portion -necessary for penetration lipid rich nerve membranes 2) Amino end (hydrophilic end) -confers water solubility -ensures solubility of local in cartridge and prevent precipitation 3) Intermediate chain (-COO-) or (-NHCO-) -provides spatial separation and divides local into esters or amides

Local Anesthesia Esters Short acting Metabolized in the plasma and tissue fluids Excreted in urine

Ester L.As are more allergic than amide L.As Local Anesthesia Amides Longer acting Metabolized by liver enzymes Excreted in urine Ester L.As are more allergic than amide L.As

Drug List Local Anesthesia Esters Cocaine. Benzocaine. Procaine. Tetracaine.

Drug List Local Anesthesia Amides Bupivacaine. Articain. Lidocaine (Xylocaine). Mepivacaine.

Properties of Local Anaesthetic Agents AMINOESTERS AMINOAMIDES Metabolism rapid by plasma cholinesterase slow, hepatic Systemic toxicity less likely more likely Allergic reaction possible - PABA derivatives form very rare Stability in solution breaks down in ampules (heat,sun) very stable chemically Onset of action slow as a general rule moderate to fast pKa's higher than PH = 7.4 (8.5-8.9) close to PH = 7.4 (7.6-8.1) Benzocaine Chloroprocaine Dyclonine Procaine tetracaine bupivacaine (Marcaine) levobupivacaine Lidocaine (Xylocaine) lidocaine-prilocaine (EMLA) mepivacaine (Carbocaine

CNS→The primary action is depression Systemic action of L.A. CNS→The primary action is depression Anticonvulsant properties Analgesia Mood elevation

Preconvulsive signs and symptoms of CNS toxicity Signs Symptoms Slurred speech Numbness of Tongue and circumoral region Shivering Warm flushed feeling of skin Tremor of muscle of face Pleasant dream like and extremities state Dizziness Visual disturbance Tinnitus Drowsiness Disorientation Signs Symptoms Slurred speech Numbness of Tongue and circumoral region Shivering Warm flushed feeling of skin Tremor of muscle of face Pleasant dream like and extremities state Dizziness Visual disturbance Tinnitus Drowsiness Disorientation

CVS Direct action of L.A. on myocardium: It will cause myocardial depression ↓ electrical excitability ↓ Conduction rate ↓ force of contraction

Direct action on peripheral vasculature Continue Direct action on peripheral vasculature Cocaine is the only local anesthetic drug that cause vasoconstriction all others produce vasodilatation.

Local tissue toxicity Skeletal muscles are subjected to the action of local anesthetic drugs more than other tissues intraoral and intramuscular injection of lidocaine,atricaine, mepivicaine, prilocaine, bupivacaine and etidocaine will produce skeletal muscle alteration.

Respiratory system At a non overdose Local anesthetic drugs have a direct relaxant action on bronchial smooth muscle At overdose level they may produce respiratory arrest as a result of generalized CNS depression

for local anesthetic agents Vasoconstrictors for local anesthetic agents

Vasodilatation Local Anesthetics Procain (highest vasodilatation effect) Vasodilatation Prilocain, mepivacain

Vasodilatator effect of local anesthetics… Increases absorbtion of anesthetic solution leading rapid move away of solution from injection area Decreases depth and duration of anesthesia Increases the plasma level of L.A that may cause possible TOXICITY Causes increased bleeding due to increased vasodilatation

Vasoconstrictor (vasopressor) agents acts opposite to local anesthetics by constricting vessels

Why adding vasoconstrictors to L.A. (Advantages of vasoconstrictors) ↓ blood flow to the site of administration Absorption of L.A. to the CVS is slowed resulting in lower level of anesthetic drug in the blood Minimize the risk of toxicity by lowering the blood level of L.A. drug ↑ duration of action ↓bleeding at side of administration

Classification of vasoconstrictors according to chemical structure Catecholamine's Noncatecholamines Epinephrine Amphetamine Nor epinephrine Methamphetamine Levonordefrin Ephedrine Isoproterenol Mephentermine Dopamine Hydroxyamphetamine Metaraminol Methoxamine phenylephrine

Classification of vasoconstrictors according to mode of action Direct acting Indirect acting Mixed acting Epinephrine Tyramine Metaraminol Norepinephrine Amphetamine Ephedrine Levonordefrin Methamphetamine Isoproterenol Hydroxyamphytamine Dopamine Methoxamine Phenylephrine

Dilutions of vasoconstrictors The most common dilutions of vasoconstrictors used in dentistry are: 1:50000 1:80000 1:10000 1:100000 1:200000 1:300000 1:400000

Epinephrine Norepinephrine

Pharmacology of vasoconstrictors EPINEPHRINE: Mode of action: Act directly on α and β receptors but more predominate on β receptor Systemic action: 1-Myocardium: Adrenaline stimulate β1 receptors of the myocardium ↑ cardiac output and heart rate

↑ incidence of dysarthmias 3-coronory arteries: Continue 2-Pacemaker cells: ↑ incidence of dysarthmias 3-coronory arteries: ↑ coronary arteries blood flow 4- BP: In small doses ↑ systolic BP, ↓ Diastolic BP In larger doses ↑ diastolic BP

Continue Cardiovascular dynamic: ↑ Systolic and diastolic pressure ↑ Cardiac output ↑ Heart rate ↑ strength of contraction

Continue 5- Vasculature: Adrenaline produce constriction of vasculatures which supplying skin, mucous membrane and kidneys While its effect on vessels supplying skeletal muscle in small doses it produce dilatation while in larger doses produce vasoconstriction 6-Hemostasis: Adrenaline is used frequently as vasoconstrictor during surgical procedures 7- Respiratory system: It’s a potent dilator of bronchiole smooth muscle

Continue 8- CNS: Side effects of overdose: In normal therapeutic doses it have no effect on CNS while in an excessive dose it stimulate CNS ↑ fear, anxiety, restlessness, headache, tremor, weakness and dizziness. Side effects of overdose: Cardiac dysarthmia Ventricular fibrillation Dramatic increase in both systolic and diastolic BP Angina episode

Clinical applications Management of acute allergic reaction Management of bronchospasm Management of cardiac arrest For haemostatic Increase depth of anesthesia Increase duration of anesthesia To produce mydriasis

Availability in dentistry Epinephrine dilution LA 1:50,000 Lidocaine 1:80,000 Lidocaine 1:100,000 Lidocaine Atricaine 1:200,000 Atricaine Bupivacaine Etidocaine Lidocaine Mepivacaine Prilocaine 1:300,000 Lidocaine

NOREPINEPHRINE (NORADRENALINE, LEVARTERENOL) Released from similar source like epinephrine Effectiveness is one fourth of epinephrine It has intensive adrenargic stimulative effect which may cause possible tissue necrosis. (especially within palatinal region in the mouth) Its use with L.A is controversial.

SYSTEMIC EFFECTS OF NOREPINEPHRINE Cardiovascular system Increases systolic and diastolic blood pressure Decreases heart rate Increases volume of heart It has no bronchodilatator effect Increases metabolism but less effective than epinephrine It causes vasoconstriction

Selection of vasoconstrictors 1-length of dental procedure. 2-Requirement of haemostatic. 3-Medical status of patient.