Pharmacology: Ch. 9 Local Anesthetics

Which is the most commonly used topical anesthetic?

Benzocaine

Which local anesthetic would be indicated for a lengthy dental procedure as a result of its long duration of action?

Bupivacaine 0.5% with 1:200,000 epinephrine -pulpal anesthesia of 90 to 180 minutes

Pharmacologic Effects: Peripheral Nerve Conduction (Blocker)

Common order of nerve function loss: • Autonomic • Cold • Warmth • Pain • Touch • Pressure • Vibration • Proprioception • Motor

Mr. Jones suffered from a myocardial infarction a year ago. He is coming to the clinic for periodontal assessment and debridement. His medications include warfarin, Prinivil, atenolol, and Cardizem. Which local anesthetic would be safest for Mr. Jones?

Lidocaine 2% with 1:100,000 epinephrine 2 Cartridges would be safe to administer

Mrs. Garza is in her second trimester of pregnancy and requires an emergency endodontic procedure. Which local anesthetic agent would be indicated for this procedure?

Lidocaine 2% with 1:100,000 epinephrine Lidocaine 2% with 1:100,000 epinephrine in the lowest effective dose possible would be indicated for the pregnant patient if local anesthetic is required. Both lidocaine and prilocaine are in the Food and Drug Administration's pregnancy category B, whereas mepivacaine, articaine, and bupivacaine are category C drugs.

Amides are metabolized in the

Liver

All of these local anesthetic agents are *esters* except which of the following? -Mepivicaine -Procaine -Propoxycaine -Tetracaine

Mepivicaine

What is the most common local adverse reaction to local anesthetic?

Physical injury at injection site such as a hematoma

Esters are largely metabolized in the

Plasma

All of these local anesthetic agents are *amides* except which of the following? -Mepivicaine -Bupivacaine -Procaine -Prilocaine -Lidocaine

Procaine Procaine is a PABA ester that is used as an antiarrhythmic agent and combined with penicillin to form procaine penicillin G. It is not used as a local anesthetic in dentistry today because of a high incidence of allergic reactions.

Vasoconstrictors are added to local anesthetics for all reasons except which of the following? -Increase depth of anesthesia -Shorten duration of action -Prolong duration of action -Reduce systemic toxicity

Shorten duration of action

Properties of the ideal local anesthetic

• Potent • Reversible • Absence of local reactions • Absence of systemic reactions • Absence of allergic reactions • Rapid onset • Satisfactory duration • Adequate tissue penetration • Low cost • Stability in solution (long shelf life) • Sterilization by autoclave • Ease of metabolism and excretion

Prilocaine (Citanest, Citanest Forte)

• Related chemically & pharmacologically to lidocaine and mepivacaine • Toluidine derivative • Less potent & less toxic than lidocaine • Has a slightly longer duration of action • *Orthotoluidine* > *methemoglobinemia* • Prilocaine 4% with/without 1:200,000 epinephrine

Bupivacaine (Marcaine)

• Related to lidocaine and mepivacaine • More potent & toxic • Advantage: Prolonged duration of action • Bupivacaine 0.5% with 1:200,000 epinephrine

Adverse Reaction: Local Effects

• Result of injection technique • Result of administration of an excessive volume too quickly • Hematoma

Dyclonine (Dyclone)

• Topical local anesthetic • Neither an ester nor an amide • Its side effects similar to those of other local anesthetics • Onset is 2 to 10 minutes • Duration is 30 to 60 minutes

Composition of Local Anesthetic Solutions

• Vasoconstrictor - Epinephrine • Antioxidant - Sodium metabisulfite, sodium bisulfite, acetone sodium bisulfite - to retard oxidation of epi • Sodium hydroxide -adjusts the pH of the solution to between 6 and 7. • Sodium chloride - makes the injectable solution isotonic • Methylparaben and propylparaben- not in dental cartridges, only multi-dose solutions

Weight calculation (based on a 2% solution on a 150 lb pt)

*Step 1:* Determine amt of anesthetic in 1 cart of solution (mg) : 2% solution= 2x 10mg/ml= 20mg/ml x 1.8 ml/cart= 36 mg/cart *Step 2:* Calculate the max recommended dose (mg/lb; 2mg/lb) 150x2= 300mg *Step 3:* Determine the max number of cartridges: 300/36= *8.3 cartridges*

What is the maximum safe dose (mg) for a cardiac patient?

0.04 mg

Which is the primary consideration when administering a local anesthetic with a vasoconstrictor to a patient with suspected cocaine abuse? (1) Cholinergic stimulation by the vasoconstrictor (2) Adrenergic stimulation by the vasoconstrictor (3) Possible myocardial infarction (4) Possible syncope

2 & 3 Cocaine is an *adrenergic agent*, which stimulates *heart rate* and *blood pressure*. *Vasoconstrictors* are also *adrenergic agonists* or sympathomimetics, which would have an *additive effect* when combined with cocaine. The use of a local anesthetic with a vasoconstrictor in a cocaine abuser could cause a *dangerous rise in blood pressure and heart rate that could cause a myocardial infection.*

Which must occur for a local anesthetic to be absorbed into the tissue? (1) Weak acid form (2) Weak base form (3) Primarily nonionized (4) Primarily ionized

2 & 3 Local anesthetics must be in a *weak base form* that is equilibrated in a fat-soluble free base and a water-soluble hydrochloric salt. The *dental cartridge is acidic (4.5)*, increasing solubility in the liquid medium. Once injected into the tissue, which is slightly basic (7.4), the amount of the free-base form increases, providing greater tissue penetration, meaning that the local anesthetic must be *primarily nonionized for tissue absorption*. If the tissue in inflamed, the pH drops, increasing the ionized portion and making the local anesthetic less effective.

Short Duration-LA

30 min pulpal • Lidocaine plain • Mepivacaine plain • Prilocaine plain

Intermediate-Duration LA

30-60 min pulpal • Mepivacaine w/ vaso • Prilocaine plain block • Prilocaine w/ vaso (60-90) • Articaine w/ vaso (60-90)

Mrs. Garza is given two cartridges of lidocaine 2% with 1:100,000 epinephrine for the endodontic procedure. What is the total dosage of local anesthetic and epinephrine administered?

72 mg lidocaine, 0.036 mg of epinephrine

Long-Duration LA

>90 min pulpal • Bupivacaine

Anesthetic calculation

Amt of LA in a 2% solution: 2% solution= 2gm/100ml *{2000mg/100ml= 20mg/ml}* *One cartridge:* 20 mg/ml x 1.8 ml/cart= *36mg/cart*

All are components of local anesthetics except which of the following? -Vasoconstrictor -Sodium chloride -Antioxidant -Antihistamine -Sodium hydroxide

Antihistamine

What two main systems are affected by local anesthetic toxicity?

CNS and Cardiovascular *CNS:* -Stimulation due to depression of inhibitory fibers= restlessness, tremors, and convulsions. -Depression due to depression of both inhibitory and facilitative fibers= resp and cardio depression, then coma *Cardiovascular:* may produce myocardial depression and cardiac arrest with peripheral vasodilation

A patient is taking cimetidine (Tagamet) for a gastric ulcer. This drug could have what clinical effect if the patient requires large doses of local anesthetic?

Decrease lidocaine metabolism Cimetidine *decreases hepatic blood flow*, *slowing the metabolism of the amides*. Although the small doses used in dentistry would probably not cause toxicity, large doses could become toxic. Cimetidine does not affect renal excretion

A 45-year-old *alcoholic patient* with suspected cirrhosis needs an extraction of a badly abscessed tooth. The amount of amide local anesthetic and other drugs should be

Decreased Patients with severe liver disease or alcoholism may be unable to break down the local anesthetic, so the amount of amide local anesthetic and other drugs should be decreased to prevent systemic toxicity.

Which is the mechanism of action of a local anesthetic?

Decreases permeability of nerve membrane, preventing depolarization Nerve impulses are transmitted when the nerve action potential opens the sodium and potassium ion channels in the nerve membrane. The inward flow of sodium ions and the outward flow of potassium ions repolarizes the membrane and closes sodium channels. Local anesthetics attach themselves to the cell membrane and decrease the permeability of the nerve membrane to the flow of sodium ions, blocking nerve conduction. Because the message of pain is not transmitted, local anesthetics do not affect the perception or the reaction to pain.

Epinephrine calculation

Epi in a ml of a 1:100,000 LA: 1000 mg/100,000 ml= 1 mg/100 ml= *0.01 mg/1 ml solution* *One cart:* 0.1 mg/ml x 1.8 ml= *0.018 mg/cart*

Amides are hydrolyzed in the blood plasma by the enzymes pseudocholinesterase and liver esterases. Patients with an atypical form of pseudocholinesterase may develop an allergic reaction.

FALSE//FALSE *Amides* are primarily metabolized in the *liver*, and *esters* are hydrolyzed to PABA by *blood plasma* pseudocholinesterase and liver esterases. Patients with an atypical form of pseudocholinesterase may develop a systemic toxicity, not an allergic reaction, although *esters have much high incidence of allergenicity.*

Amides are the local anesthetics most likely to cause an allergic reaction. This property is a result of their metabolism into paraaminobenzoic acid (PABA).

FALSE//FALSE Amide local anesthetics rarely cause an allergic reaction. Esters are metabolized into paraaminobenzoic acid (PABA), causing esters to have a much greater allergic potential.

A rapid rate of injection will increase the rate of absorption at the injection site, decreasing local anesthetic blood levels.

FALSE//TRUE The faster the rate of injection is, the less the local area can accept the volume injected. This decreases the amount of local anesthetic that enters systemic circulation.

Lidocaine may be administered in by all routes except which of the following? -Topical -Intramuscular -Intravenous -Infiltration -Spinal

Intramuscular

What is the major advantage of amide local anesthetics over esters?

Lack of allergenicity

Which is the most common formulation of local anesthetic used in dentistry today?

Lidocaine 2% 1:100,000

Vasoconstrictors

• *Reduces the blood supply to the area* • *Limits systemic absorption* • *Reduces systemic toxicity* • Prolong the duration of action • Increase the depth of anesthesia • Delay systemic absorption • Reduce the toxic effect in the systemic circulation • Reduce the bleeding in the area of injection and improve visibility at surgical site • The decision about whether epinephrine should be used is made by weighing the risks and benefits

Vasoconstrictors: Drug Interactions

• *Tricyclic antidepressants* -Administration of epinephrine may produce an exaggerated increase in pressor response • *Nonselective β-blockers* -Administration of epinephrine may produce hypertension and reflex bradycardia • *Monoamine oxidase inhibitors (MAOIs)* • *Phenothiazines*

Pharmacokinetics

• Absorption depends on its route • Rate of absorption depends on vascularity of the tissues • Degree of inflammation present • Vasodilating properties of the local anesthetic agent • Presence of heat • Use of massage • Mucous membranes or denuded (abrasion,trauma) surface = increased absorption • Absorption is also determined by the proportion of the agent present in the *free-base form (nonionized)*

Lidocaine and Prilocaine (Oraquix)

• Amides: Lidocaine and prilocaine (injection-free local anesthesia) • Duration of action - 20 minutes • Onset of action - 30 seconds

Tetracaine (Pontocaine)

• An ester of PABA • Slow onset • Long duration • Estimated to have at least 10 times the potency and toxicity of procaine • Available in various sprays, solutions, and ointments for topical application

Adverse Reaction: Malignant Hyperthermia

• An inherited disease that is transmitted as an autosomal-dominant gene • Acute rise in calcium > muscular rigidity, metabolic acidosis, and extremely high fever • Treatment includes supportive measures and the administration of dantrolene (Dantrium) • Halothane & succinylcholine are contraindicated

Articaine (Septocaine)

• Approved for use in U.S. in 2000 • Derived from thiophene • Greater lipid solubility • Hydrolyzed by plasma esterase • Metabolized mainly in blood • Excreted by kidneys • Half-life is 20 minutes • May cause *methemoglobinemia* • Paresthesia • Used for local, infiltrative, and conductive anesthesia • Articaine 4% 1:100,000 epinephrine in a 1.7-ml cartridge unlike the more common 1.8-ml dental cartridge • Articaine 4% 1:200,000

Lidocaine (Xylocaine)

• Available as base or hydrochloride salt • The base is preferred when large areas of the mucosal surface are ulcerated, abraded, denuded, or erythematous • The hydrochloride salt is water soluble and penetrates the tissue better

Topical Anesthetics

• Benzocaine, an ester, is the most commonly used topical anesthetic • Lidocaine, an amide, is the second most commonly used

What people are more susceptible to the adverse reactions of the local anesthetic agents?

• Children • Elderly • Debilitated person

Adverse Reactions

• Drug: Inherent toxicity and amount of vasodilation • Concentration • Route of administration • Rate of injection • Vascularity: presence of infection/inflamm • Patient's weight • Rate of metabolism and excretion

Adverse Reaction: Pregnancy & Nursing Considerations

• Elective dental treatment should be rendered before a patient becomes pregnant • Lidocaine -FDA pregnancy category B • Prilocaine -FDA pregnancy category B • Mepivacaine -FDA pregnancy category C • Articaine -FDA pregnancy category C • Bupivacaine -FDA pregnancy category C

Lidocaine (Xylocaine, Octocaine)

• Introduced in 1948 • Rapid onset • Good distribution • Lidocaine 2% with vasoconstrictor - medium duration

Mepivacaine (Carbocaine, Polocaine, Isocaine)

• Introduced in 1960 • Its rate of onset, duration, potency, and toxicity are similar to those of lidocaine • Not effective topically • Used for infiltration, block, spinal, epidural, and caudal anesthesia • Mepivacaine 2% with 1:20,000 levonordephrin (Neo-Cobefrin) as a vasoconstrictor • Mepivacaine plain can be used to avoid vasoconstrictors

Esters

• No esters are currently available in a dental cartridge • Benzocaine: Commonly used topically

Adverse Reaction: Allergy

• Obtain allergy history • Esters have a much greater allergic potential • Unknown if amides produce allergic reactions • Diphenhydramine (Benadryl) -1% plus 1:100,000 • Methylparaben - no longer in cartridges • Sulfite

Procaine (Novocain)

• PABA ester • Used as an antiarrhythmic agent • Combined with penicillin to form procaine penicillin G • Procaine is not used in dentistry today