Page 1 of 20 Pharmacological Considerations for Implant Dentistry Jason H. Goodchild, DMD Pharmacological Considerations ♦ Local Anesthesia ♦ Pre-operative Antibiotics ♦ Peri-operative Corticosteroids Local Anesthesia – Historical Perspective Cocaine was the first local anesthetic, discovered by Carl Koller in 1884 (eye drops) The first dental use was by Dr. William Halsted on Nov 26, 1884 The “caines” developed subsequent to cocaine have no relationship to cocaine other than an etymological and pharmacological one; that is they cause anesthesia. Structure-Activity Relationship 1. Aromatic portion– Responsible for lipophilicity of compounds, i.e., lipid/water distribution and protein binding characteristics. 2. Intermediate linkage– connected to aromatic residue via an ester or amide linkage. Type of linkage important in determining the route of metabolism and the allergic potential of the compounds. 3. Amine portion– usually a secondary or tertiary amine and is associated with water solubility of the compounds, but is not necessary for anesthetic activity. Compounds lacking the amine portion are insoluble in water and useful only topically.
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Pharmacological Considerations for Implant Dentistry Jason H. Goodchild, DMD
Local Anesthesia – Historical Perspective Cocaine was the first local anesthetic, discovered by Carl Koller in 1884
(eye drops) The first dental use was by Dr. William Halsted on Nov 26, 1884 The “caines” developed subsequent to cocaine have no relationship to
cocaine other than an etymological and pharmacological one; that is they cause anesthesia.
Structure-Activity Relationship 1. Aromatic portion– Responsible for lipophilicity of compounds, i.e., lipid/water distribution and protein binding characteristics. 2. Intermediate linkage– connected to aromatic residue via an ester or amide linkage. Type of linkage important in determining the route of metabolism and the allergic potential of the compounds. 3. Amine portion– usually a secondary or tertiary amine and is associated with water solubility of the compounds, but is not necessary for anesthetic activity. Compounds lacking the amine portion are insoluble in water and useful only topically.
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Principles of Local Anesthetics Mechanism of Action: Local anesthetics block the sensation of pain by interfering with the propagation of impulses along peripheral nerve fibers. This is accomplished by a reduction in the permeability of the nerve cell membrane to sodium ions. This results in a decreased rate of rise in the depolariztion phase of the action potential causing a failure of a propagated action potential to develop.
++++++++0.70.7--2.32.30.30.3--1.31.3NoneNonePostganglionicPostganglionicType C: Type C: SympatheticSympathetic
++++++++0.50.5--2.32.30.40.4--1.21.2NoneNonePainPainType C: Type C: Dorsal RootDorsal Root
++++++++33--1515<3<3LightLightPreganglionicPreganglionicautonomicautonomicType BType B
Diameter Diameter ((ųųmm))MyelinationMyelinationFunctionFunctionFiber TypeFiber Type
Relative size and susceptibility to block of nerve fibers
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Factors affecting Local Anesthetic action:
- pKa - Lipid Solubility - Protein Binding - Vasodilator Activity - Principles of Local Anesthetics
pKa All LA are weak bases with a pKa range of 7.7-8.9. All LA molecules exist in 2 states: A free base (uncharged) that readily penetrates connective tissues and lipid-rich membranes; and a cation (positively charged species) that is unable to cross membranes. When the pH=pKa then the proportion of the two species is 50:50. If pKa increases, or the pH of the surrounding environment decreases then a greater proportion of the charged form will exist. Example…
98% Cationic species – IMPERMEABLE
2% Uncharged species
Lidocaine pKa =7.8
Injected into an inflamed area with pH=6.0
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Relationships between pKa, Ionization, and Local Anesthesia onset at pH 7.4
Drug pKa % Cationic % Free Base Onset time (min)
Mepivicaine 7.7 67 33 2-4
Lidocaine 7.8 71 29 2-4
Prilocaine 7.8 71 29 2-4
Articaine 7.8 71 29 2-4
Etidocaine 7.9 76 24 2-4
Bupivicaine 8.1 83 17 5-8
Hersh EV. Local Anesthetics. In: Fonseca RJ. Oral and Maxillofacial Surgery, 2000
Lipid Solubility The major determination of potency for LA is their intrinsic lipid solubility. The general rule is: More lipid solubility = More potency. As a result, agents with lower solubility are generally marketed at higher concentrations.
Relationships between lipid solubility and clinically effective LA concentration
Drug Lipid Solubility Concentration (%)
Articaine 40 4
Mepvicaine 42 2-3
Prilocaine 55 4
Lidocaine 110 2
Bupivicaine 560 0.5
Etidocaine 1853 1.5
Adapted from: Jastak JT et al. Local Anesthesia of the Oral Cavity, 1995.
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Protein Binding Increased protein binding allows anesthetic molecules to be more firmly attached to proteins at receptor sites. The general rule is: Increased protein binding = longer duration of action. Duration of Local anesthesia is based on several factors:
- Affinity of the LA to the nerve membrane (Lipid and protein components) - Type of injection - Presence or absence of vasoconstrictor - Pulpal vs. soft tissue anesthesia?
Protein Binding Characteristics and Duration of Action
Agent Approx. Protein Binding
Duration of action (mins)
Prilocaine 55 40-220
Lidocaine 65 60-190
Mepivacaine 75 25-165
Etidocaine 94 30-470
Bupivacaine 95 40-440
Articaine 95 60-220
Adapted from: Malamed SF. Handbook of Local Anesthesia, 1990. and Jastak JT. Local Aneshesia of the Oral Cavity, 1995.
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Average Durations of Local Anesthesia after Intraoral Injection (mins)
Remains the safest local anesthetic for children is lidocaine with 1:100,000 epi Maximum dose is 1 cartridge per 25 pounds (~10kg)
Concentrations of Lidocaine
* 1:50,000 should be reserved for local hemostasis
† Max no. of carps is limited by the LA
Hersh EV. Local Anesthetics. In: Fonseca RJ. Oral and Maxillofacial Surgery, 2000
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RULE of 25? Quick and easy way to estimate maximum Quick and easy way to estimate maximum
local anesthetic doseslocal anesthetic doses Calculation yields a dose that will always be Calculation yields a dose that will always be
less than the MRDless than the MRD
In healthy patients, the In healthy patients, the ““Rule of 25Rule of 25”” states states a practitioner can use 1 a practitioner can use 1 carpulecarpule of any local of any local anesthetic formulation for every 25 lbs of anesthetic formulation for every 25 lbs of body weightbody weight
Dent Clin N Am 2010;54:587–599.
Pregnancy and Breastfeeding Risk Classification of Local Anesthetics
Drug Pregnancy Category Use during breastfeeding?
Lidocaine B Yes
Mepivacaine C Yes
Prilocaine B Yes*
Bupivacaine C Yes
Etidocaine B Yes
Articaine C With Caution
JADA 2012;143:858-71.
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Pregnancy and Breastfeeding Risk Classification of TOPICAL Local Anesthetics
Drug Pregnancy Category Use during breastfeeding?
Lidocaine B Yes
Dyclonine C Yes
Benzocaine C With Caution
Tetracaine C With Caution
JADA 2012;143:858-71.
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Local Anesthesia: Minimizing Complications and Maximizing Success Considerations for Mandibular Local Anesthetic Failures
♦ Anxiety & Fear ♦ Infection ♦ Too little volume of anesthetic ♦ Central Core Theory ♦ Lack of understanding of technique or local anatomy ♦ Variations in anatomy ♦ Sphenomandibular Ligament ♦ Nerve of the Mylohyoid ♦ Gonial Angle of the Mandible
Highly Anxious Patients “Factors such as fear are clearly capable of influencing patient response to painful or other stimuli applied after administration of a local anesthetic. The relationship between these variables may be reciprocal: fear can lead to inadequate anesthesia and being treated with inadequate anesthesia can increase fear” Source: Milgrom P, Weinstein P, Getz T. Treating Fearful Dental Patients. 2nd Ed. Seattle, WA: University of Washington Press; 1995:p219. “There is a direct relationship between anxiety and acute pain. Increases in anxiety increase sensitivity to pain. Conversely, reductions in anxiety reduce the perception of pain ” Source: Anesth Prog. 1991;38:120-127. “Apprehension is learned but pain is perception. For patients who would otherwise experience no stimulus after an effective anesthetic injection, even the slightest perception is painful. A feeling of pressure or touch can create an expectation of pain, eliciting a response from the patient. ” Source: Feck AS. Goodchild JH. Compendium 2005;26(3):81-7. Infection
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Volume of Anesthetic In general the volumes of local anesthetic should be: (Br Dent J 1999;186(1):15-20.) Infiltrations: approximately 1.0mL IANB: approximately 1.5mL Palatal or long buccal: 0.2-0.5mL Relative size and susceptibility to block of nerve fibers
Fiber Type Function Myelination Diameter (ųm)
Conduction Velocity
(m/s)
Sensitivity to Block
Type A: Alpha Proprioception, motor Heavy 12-20 70-120 +
Type A: Beta Touch, pressure Heavy 5-12 30-70 ++
Type A: Gamma Muscle spindles Heavy 3-6 15-30 ++
Type A: Delta Pain, temperature Heavy 2-5 12-30 +++
Type B Preganglionic autonomic Light <3 3-15 ++++
Type C: Dorsal Root Pain None 0.4-1.2 0.5-2.3 ++++
Type C: Sympathetic Postganglionic None 0.3-1.3 0.7-2.3 ++++
Source: Morgan GE, et al. Clinical Anesthesiology. 4th Ed. 2005.
Local Anesthetics Preferably Block Small Nerve Fibers
Coverage of 3 nodes is needed to stop conduction
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What about injection speed? Does injection speed impact efficacy? Kanna MD, et al (2006)
♦ 38 subjects ♦ Crossover Design (1 week apart) ♦ 27ga long needle ♦ Slow IANB (delivered over 60 secs) ♦ Rapid IANB (delivered over 15 secs)
Central Core Theory Nerves on the outside of the nerve bundle (mantle fibers) supply molar teeth. More centrally located nerve fibers (core fibers) innervate the incisors. Local anesthetic placement near to the IAN may diffuse and block the outermost fibers but will not block the inner fibers. May lead to incomplete mandibular anesthesia Incisors may not achieve complete anesthesia. May require mental or incisive block in addition to IANB. Or buccal + lingual infiltration Source: JADA 2011;142(suppl 9):3S-7S. Anesthesiology 1976;45:421-44. Consequences of improper needle placement during traditional IANB Too Low: An injection too far below the lingula will result in lingual anesthesia with inadequate anesthesia of the teeth or bony structures
Central Core Theory?Onset of Onset of PulpalPulpal AnesthesiaAnesthesia
Position of the lingula in comparison to the occlusal plane (Oral Surg Oral Med Oral Pathol 1952;5:966–88.)
♦ In 16% of mandibles, the lingula was less than 1 mm above the occlusal plane ♦ 48% were from 1 to 5 mm above the occlusal plane ♦ 27% were from 9 to 11 mm above the occlusal plane ♦ 4% were from 11 to 19 mm above the occlusal plane ♦ A needle inserted 5 mm above the occlusal plane and parallel to it would lie above the
lingula in 64% of mandibles and below it in 36%. A needle placed 11 mm above the occlusal plane would be above the lingula in 96% of mandibles
Too Deep (posteriorly): If an injection is made too deeply, the solution may be deposited into the parotid gland resulting in facial nerve anesthesia and paralysis, without mandibular nerve anesthesia Too Mesial: An injection too far mesially will cause anesthetic failure because the solution will be deposited into the media lpterygoid muscle. In addition to anesthetic failure it may cause muscle inflammation and trismus
Direction of IANB
Too Superficial: The solution may be deposited too distant from the lingula and the inferior alveolar nerve. May result in lingual anesthesia but inadequate anesthesia to the teeth Too High: Solution may be deposited into the sigmoid notch, inadequate/no anesthesia would be the result
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Intravascular: If all of part of the local anesthetic solution is deposited intravascularly, local anesthesia may be inadequate. Possible complications include:
♦ Hematoma ♦ Pain ♦ Trismus (also the result of penetrating the medial pterygoid muscle) ♦ Effects 2° to the drugs itself (local anesthetics and/or vasoconstrictor)
Positive aspiration is infrequent during IANB (2.6-30%). Technique of alternating injection/aspiration is recommended (JADA 1992;123:69-73.) Lack of understanding of local anatomy, variations in anatomy
Anatomy of the pterygomandibular space
Source: JADA 2003;134:888-93.
BORDERS OF THE PTERYGOMANDIBULAR SPACE Inferior and Medial: medial pterygoid muscle Anterior: pterygomandibular raphe Superior: lateral pterygoid muscle Lateral: mandibular ramus Posterior: parotid gland
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CONTENTS OF THE PTERYGOMANDIBULAR SPACE Inferior alveolar nerve IA artery and vein Lingual Nerve Sphenomandibular ligament Buccal nerve Mylohyoid nerve Mylohyoid artery and vein Anatomy of the pterygomandibular space
Diagrammatic representation of a transverse section of the right mandibular ramus at the level at which an IANB would be given
Source: Clin Anat 2010;23:936–944.
Diagrammatic representation of the right inferior alveolar neurovascular bundle at the level of the lingual
Source: Clin Anat 2010;23:936–944.
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Recommended insertion of needle for traditional IANB is 1 inch (25.4mm) Average length of short needles: 21.5 mm (hub to tip) Average length of long needles: 33 mm (hub to tip)
Summary of Statistics
Position of the NVB in relation to the anterior border of the ramus expressed as a ratio of total ramal anteroposterior diameter
0.60 ± 0.07
Direct distance between IAN and LN (mm) 8.5 ± 2.4
Anterior displacement of the LN from the IAN (mm) 7.3 ± 2.5
Mediolateral displacement of the LN from the IAN (mm) 3.9 ± 1.6
Source: Clin Anat 2010;23:936–944
Sphenomandibular Ligament Upper attachment on the sphenoid spine, sometimes extending to the petrotympanic fissure and malleus Lower attachment is to the mandibular lingula May be a septum of the pterygomandibular space Barrier against LA!
7.3mm
3.9mm
8.5mm
IAN
LN
Masseter
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Sphenomandibular Ligament: Lower attachment is to the mandibular lingula There is significant variation regarding the lower attachment: The SML may also attach to the inferior margin of the mandibular foramen, extending superiorly and posteriorly to the posterior border of the mandible, up the condyle where it can merge with stylomandibular ligament The mylohyoid nerve passes medially and behind the ligament before passing into the mylohyoid groove of the ramus In one study, 60% of SML studied extended from the anterior border of the lingula to the posterior border of the ramus Source: Cranio 2007;25(3):160-5. Dent Clin N Am 2012;56:133–148. Mylohyoid Nerve (MN)
♦ The nerve to the mylohyoid is derived from the mandibular division of the trigeminal nerve
♦ It provides motor supply to the mylohyoid and digastric muscles ♦ MN splits superiorly to the mandibular foramen (~13-14mm), and passes along the
mylohyoid groove (which is parallel to the mandibular canal) ♦ It has long been suspected that the mylohyoid nerve is a mixed motor and sensory nerves
supplying accessory innervation to the mandibular teeth ♦ It may join with the lingual nerve ♦ It also may enter the mandible through foramen in the symphysis or premolars, in this
case it may terminate directly into the mandibular teeth or join with the incisive nerve Source: Clin Anat 2010;21:591-5. Aust Endod J 2001;27(3);109-11.
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Inferior Alveolar Nerve
Lingual Nerve
Mylohyoid Nerve
Anesthetizing the Mylohyoid Nerve (MN) The nerve may be anesthetized by infiltrating the soft tissue over the disto-lingual root surface of the tooth requiring treatment; or simply under the lingual mucosa adjacent to the tooth requiring treatment Goal is to bathe the nerve as branches of it enter the lingual surface of the mandible
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Gonial Angle of the Mandible Several studies have looked at the relationship between the gonial angle and the position of the mandibular foramen Average gonial angle among the publications was 120.4° Gonial angle was inversely related to the anterior-posterior width of the ramus and the distance from the mandibular foramen to the mandibular border For patients with a wide gonial angle, the IANB is accomplished lower and possibly with a smaller needle. For patients with a narrow gonial angle, the IANB is accomplished higher and possibly with a larger needle Effect of Age on Gonial Angle: Gonial angle decreased significantly with age (approximately 140° to 120°) . Also, with increasing age the mandibular foramen moves anteriorly approximately 5.5mm. Mandibular foramen increases in size by 40% from childhood to adulthood. Source: Int J Morphol 2009;27(4):1305-11. Anat Rec 1985;212(1):110-2. West Ind Med J 2002;51(12):14.
