Pharmacology of Local Anesthesia(Mode of Action, dosage and Available Forms)Dr. Ana Maria Ospina. Department of Oral and Maxillofacial Surgery NOVA Southeastern University

Local AnesthesiaA loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings or an inhibition of the conduction process in peripheral nerves, without inducing a loss of consciousness.

Depressant

effect on excitable membranes

L.A. are chemicals that reversible block action potentials in excitable membranes. All drugs regardless of the route of administration must enter into the circulatory system before they begin to exert a clinical action; L.A. however cease to provide a clinical effect when they are absorb from the site of administration into the circulation.

All local anesthetics produce a peripheral vasodilation local blood flow rate of absorption blood levels depth and duration bleeding

Pharmacological Characteristics

Three components common to LAs:

Aromatic Lipophilic Group (Hydrophobic). Intermediate chain > Either ester or amide. Hydrophilic Amino Group.

Esters of benzoic acid:Butacaine Cocaine Ethyl aminobenzoate (benzocaine) Hexylcaine Piperocaine Tetracaine

Esters paraaminobenzoic acid:Chloroprocaine Procaine Propoxycaine

Amide Articaine Bupivacaine Dibucaine Etidocaine Lidocaine Mepivacaine Prilocaine Ropivacaine Quinoline Centbucridine (

Composed ofEsters:

Amides:

Cocaine Ethyl Aminobenzoate (Benzocaine) Tetracaine Procaine Propoxycaine

Lidocaine (Xylocaine) Mepivacaine (Carbocaine) Prilocaine (Citanest) Bupivacaine (Marcaine) Etidocaine (Duranest) Articaine (Septocaine)

UPTAKE of local anesthetic molecules

Factors that influence the uptake:

Access of the agent: Topical

application. Injection.

Closeness of the solution to the nerve. Diameter of the nerve. Vascularity Vasoactivity and concentration

Blood level is influenced by

Rate of absorption Rate at which the drug is absorbed into cardiovascular system

Blood level is influenced by

Rate of distribution (From vascular compartment to tissues, more rapid in healthy patients)

Blood level is influenced byDISTRIBUTIONThroughout the body to all tissues... Highly perfused organs, higher blood levels

Blood level is influenced by

Elimination (metabolic or excretory)

Time to Achieve Peak Blood LevelRouteIntravenous

Time1 min

IntramuscularTopical Subcutaneous

5-10 min5 min 30-90 min

Metabolism Overall

toxicity depends on a balance between its rate of absorption and its rate of removal

Metabolism (Biotransformation)

EsterHydrolyzed by the enzyme

Pseudocholinesterase

AmideMetabolism occurs in the liver.

Contraindications

Absolute: under no circumstance should the drug be administered Relative: May be administered after weighing the risk and benefits

Contraindications(relative vs. absolute) For EstersAtypical form of Pseudocholinesterase. (1/2800 person) PABA allergy Significant liver dysfunction, or Heart failure. ASA IV Allergy

For Amides

Contraindications for Local Anesthetics

Doubt: medical consultation to be sought

The biotransformation products of some LAs can cause certain clinical activity if they are permitted to accumulate in the blood. E.g., large doses of PrilocaineOrthotoluidine Methemoglobin Methemoglobinemia

Methemoglobinemia

Blood appears chocolate brown Deficient delivery Oxygen to tissues Cyanosis like state Respiratory depression Syncope Treatment: IV Methylene blue

Duration of ActionFactors:

Individual response to the drug. Accuracy in deposition of the local anesthetic. Anatomical variation. Status of the tissues at the site of drug deposition. Type of L.A. administered. Vasoconstrictor.

Excretion

Occurs mainly in the kidneys. 12-24 hours. Patients with significant renal impairment

Components for a cartridge of local anesthesia:

Each cartridge has 1.7 ml solution Local Anesthetic Agent. Sodium Chloride. (Alkalinizing Agent) Vasoconstrictor (and Antioxidant) Sterile water. (diluent)

Local Anesthetics Available in United States(Cartridges)Local Anesthetic + Vasoconstrictor Articaine 4% + epinephrine 1:200,000 1:100.000 Bupivacaine 0.5% + epinephrine 1:200,000

Duration of Action Intermediate ( ~ 60 min) Long (more than 90 min) Short (less than 30 min) Intermediate Intermediate

Lidocaine 2% 2% + epinephrine 1:50,000 2% + epinephrine 1:100,000Mepivacaine 3% 3% + levonerphrine 1:20.000 Prilocaine 4% 4% + epinephrine 1:200,000

Short IntermediateShort Intermediate

Local Anesthetics Available in United States (Other presentations)Local Anesthetic

Lidocaine (2%, 2.5%, 4%, 5%) /Prilocaine 2.5%Benzocaine 20%, 18% and 16%Benzocaine 14% + Butamben 2%

GelSpray

Gel Tetracaine 2% Gel Bupivacaine 0.5%, 0.25% Mepivacaine 1%, 2% Lidocaine 1%, 2%

Multi vials

Dosages

Maximum Recommended Dosages (MRDs) of Local Anesthetics Available in North America

MRD

The least concentrate solution that produce effective pain control should be used

Recommended Maximum Local Anesthetic Doses Hupp et al.

Cartridge1.7 ml of local anesthetic solution (USA) How to calculate # of mg of LA in a cartridge? By multiplying: Percent Concentration x 1.7 ml Example: Lidocaine 2% 2 % = 20 mg/ml 20 mg/ml x 1.7 (ml) = 34 mg of anesthetic agent in the cartridge.

Cartridge

Lidocaine Mepivacaine Articaine Bupivacaine

2% 3% 4% 0.5%

2 % = 20 mg/ml 3 % = 30 mg/ml 4 % = 40 mg/ml 0.5 % = 5 mg/ml

Case 122 Years old, healthy, 70 kg.Lidocaine 2 % = 34 mg in 1 cartridge (20mg/ml x 1.7 ml = 34 mg ) Maximum # mg / kg = 5 mg /kg

70 kg x 5 mg/kg = 350 mg 350/34 = 10 cartridges

Case 26 years old, healthy, 28 kgMepivacaine 3 % = 51 mg in 1 cartridge (30mg/ml x 1.7ml = 51 mg) Maximum = 5 mg/kg

28 kg x 5 mg/kg = 140mg / 51mg = 2.7 cartridges ofMepivacaine

Case 355 years old, healthy, 90 kgArticaine 4 % = 68 mg in 1 cartridge (40mg/ml x 1.7ml = 68 mg) Maximum = 7.0 mg/kg

90 kg x 7.0mg/kg = 630mg / 68mg =9.2 cartridges

Case 455 years old, healthy, 90 kgBupivacaine 0.5 % =8.5 mg in 1 cartridge (5mg/ml x 1.7ml = 8.5 mg) Maximum = 1.5 mg/kg

90 kg x 1.5mg/kg = 135mg / 8.5mg = 15 cartridges

Overdose

Administration of too large local anesthetic dose in relation to the age and weight of the patient. Overwhelming majority of cases: in children.

* All L.A. readily cross

blood-brain barrier plancenta

CNS: Toxic: Tonic-clonic convulsion CVS: Toxic: Cardiac arrest

Respiratory: Toxic: Respiratory arrest

Nothing that is done for a patient is of greater importance than the administration of a drug that prevents pain during treatment

Bibliography

Handbook of Local Anesthesia , Fifth Edition Stanley F. Malamed (Vital Source)

Thanks for your Attention ...!