13.1 Local Anesthetics & Vasoconstrictors
Key Takeaways
- Amide LAs (lidocaine, articaine, mepivacaine, bupivacaine, prilocaine) undergo primarily hepatic metabolism; esters (benzocaine, procaine) are hydrolyzed by plasma cholinesterases and historically show more allergic potential.
- Onset relates to pKa and tissue pH (non-ionized base crosses nerve membrane); duration tracks protein binding, lipid solubility, and vasoconstrictors—inflamed acidic tissue impairs infiltration anesthesia.
- Know cartridge math (2% ≈ 36 mg/1.8 mL; 4% ≈ 72 mg) and teaching MRDs: lidocaine/articaine ~7 mg/kg with vaso, mepivacaine ~4.4–6.6 mg/kg, bupivacaine ~1.3–2 mg/kg, with absolute caps.
- Epinephrine 1:100,000 delivers ~18 μg/cartridge vs ~9 μg at 1:200,000; limit or avoid exogenous epi in unstable cardiovascular disease, uncontrolled hyperthyroidism, cocaine intoxication, and relevant drug interactions.
- Methemoglobinemia is classically linked to prilocaine and benzocaine—cyanosis with chocolate-brown blood; treat supportively and with methylene blue when indicated.
13.1 Local Anesthetics & Vasoconstrictors
Quick Answer: Dental local anesthetics (LAs) are mostly amides (hepatic metabolism) rather than esters (plasma esterases; more allergy). Onset tracks pKa and tissue pH (lower pKa / more non-ionized base → faster entry). Duration tracks protein binding and lipid solubility, amplified by vasoconstrictors. Know cartridge math, maximum recommended doses (lidocaine, articaine, mepivacaine, bupivacaine, prilocaine), epinephrine 1:100,000 vs 1:200,000, absolute/relative epi contraindications, and methemoglobinemia risk with prilocaine/benzocaine.
Pharmacology is a major AFK slice (~14% of the blueprint when grouped with systemic drugs and emergencies). Local anesthesia items test mechanism, drug selection, dose safety, vasoconstrictor decisions in medically compromised patients, and recognition of toxicity/methemoglobinemia—not memorization of obscure brand names alone.
Mechanism of Action
Local anesthetics block voltage-gated sodium channels on nerve axons from the inside of the membrane (use-dependent block). The non-ionized (free base) form crosses the lipid nerve membrane; inside the axoplasm the ionized (cationic) form binds the channel and prevents Na⁺ influx → no depolarization → no propagation of pain, temperature, and other sensory (and, at high concentration, motor) impulses.
Clinical implications of the mechanism:
| Concept | Chairside meaning |
|---|---|
| Inflamed/acidic tissue | More drug ionized outside the nerve → poor penetration → “hot tooth” failures with infiltration |
| pKa | Fraction non-ionized at physiologic pH; lower pKa generally faster onset |
| Lipid solubility | Potency and often longer duration (nerve membrane partitioning) |
| Protein binding | Correlates with duration of action |
| Vasodilation | Most LAs dilate vessels → ↑ systemic absorption → shorter block unless vasoconstrictor added |
Nerve fiber susceptibility (teaching order, not absolute): small myelinated fibers and unmyelinated C fibers for pain/temperature are more readily blocked than large motor fibers—patients may still feel pressure/vibration while pain is abolished.
Amides vs Esters
| Feature | Amides | Esters |
|---|---|---|
| Common dental examples | Lidocaine, articaine*, mepivacaine, bupivacaine, prilocaine | Procaine, tetracaine, benzocaine (topical), cocaine (historical) |
| Metabolism | Primarily hepatic microsomal enzymes | Plasma pseudocholinesterase (and tissue esterases) |
| Allergy potential | True IgE allergy rare; reactions often to preservatives/vasoconstrictor | Higher historic allergy rate (PABA metabolites) |
| Cross-reactivity | Within amide class uncommon but possible | Cross-reactivity among esters more likely |
| AFK default | Nearly all injectable dental LAs | Mostly topicals (benzocaine) in modern practice |
*Articaine is an amide with an additional thiophene ring and an ester side chain hydrolyzed in plasma—short plasma half-life, but classified and used as an amide injectable.
Allergy teaching points:
- Documented true LA allergy is uncommon; many “allergies” are syncope, epinephrine effects, or toxicity.
- If a true amide allergy is proven, consider ester alternatives or allergy/anesthesia referral—do not casually switch without history.
- Methylparaben (multi-dose vials) and sulfites (with epinephrine) can cause reactions mistaken for LA allergy.
- Sodium bisulfite/metabisulfite antioxidant accompanies epinephrine—relevant in sulfite-sensitive asthmatics.
pKa, Onset, Duration, and Potency
| Property | Effect on clinical block | High-yield examples |
|---|---|---|
| pKa close to tissue pH (more free base) | Faster onset | Mepivacaine pKa ~7.6; lidocaine ~7.7; bupivacaine ~8.1 (slower onset) |
| High lipid solubility | Greater potency; often longer block | Bupivacaine highly lipid soluble |
| High protein binding | Longer duration | Bupivacaine ~95% protein bound |
| Intrinsic vasodilation | Shorter plain duration | Lidocaine dilates; mepivacaine less so (usable plain) |
| Tissue inflammation (↓ pH) | Delayed/failed onset | Infected molar infiltration failures |
Mnemonic structure for AFK recall:
- Onset ≈ pKa + tissue pH + proximity to nerve
- Duration ≈ protein binding + lipid solubility + vasoconstrictor + vascularity of site
- Potency ≈ lipid solubility
Buffered LA (alkalinization) increases free base fraction and may speed onset and reduce injection pain—conceptually tested more than brand protocols.
Core Injectable Agents and Maximum Doses
Doses below are widely taught dental maximum recommended doses (MRDs). Always use the lower of weight-based or absolute maximum, reduce for children/frail/elderly/hepatic disease, and count all cartridges of all agents. Canadian and US teaching numbers are close; know the table and the arithmetic.
| Agent | Typical dental concentration | Approx. MRD (teaching) | Notes |
|---|---|---|---|
| Lidocaine | 2% ± epi 1:100k or 1:50k | 7 mg/kg with epi (absolute often 500 mg); ~4.4 mg/kg plain | Gold-standard amide; intermediate duration with epi |
| Articaine | 4% ± epi 1:100k or 1:200k | 7 mg/kg (absolute often 500 mg) | Excellent bone diffusion; infiltration often effective in mandible; rare paresthesia association debated with 4% solutions |
| Mepivacaine | 3% plain or 2% with levonordefrin 1:20k | ~4.4 mg/kg plain; ~6.6 mg/kg with vaso | Prefer when epinephrine should be minimized; shorter plain duration |
| Bupivacaine | 0.5% ± epi | ~1.3–2 mg/kg (absolute often 90 mg) | Long duration; post-op pain control; higher cardiotoxicity risk |
| Prilocaine | 4% ± vaso (felypressin in some markets) | ~6–8 mg/kg (absolute often 400–600 mg by source) | Methemoglobinemia risk at high dose |
Cartridge arithmetic (must be automatic)
- Standard dental cartridge ≈ 1.8 mL (some systems 1.7–2.2 mL—read label).
- 1% solution = 10 mg/mL.
- Therefore 2% lidocaine = 20 mg/mL × 1.8 mL ≈ 36 mg LA per cartridge.
- 4% articaine = 40 mg/mL × 1.8 mL ≈ 72 mg LA per cartridge.
- 0.5% bupivacaine = 5 mg/mL × 1.8 mL ≈ 9 mg LA per cartridge.
Worked example: 70 kg adult, lidocaine 2% with epi, MRD 7 mg/kg → 490 mg (cap 500) → 490/36 ≈ 13 cartridges theoretical maximum—never approach this clinically; use the fewest cartridges for profound anesthesia and factor other agents already given.
Pediatric trap: weight-based MRD falls fast; 20 kg child at 7 mg/kg lidocaine with epi = 140 mg ≈ 3–4 cartridges—easy to exceed if multiple quadrants are treated carelessly.
Vasoconstrictors: Epinephrine Concentrations
Vasoconstrictors slow systemic absorption, deepen and prolong anesthesia, reduce bleeding in the field, and allow higher effective LA doses within safety limits by lowering peak plasma levels.
Epinephrine math
| Concentration | Epinephrine per mL | In 1.8 mL cartridge |
|---|---|---|
| 1:50,000 | 0.02 mg/mL (20 μg/mL) | 0.036 mg (36 μg) |
| 1:100,000 | 0.01 mg/mL (10 μg/mL) | 0.018 mg (18 μg) |
| 1:200,000 | 0.005 mg/mL (5 μg/mL) | 0.009 mg (9 μg) |
1:100,000 vs 1:200,000:
| Issue | 1:100,000 | 1:200,000 |
|---|---|---|
| Soft-tissue/pulpal duration | Slightly longer / denser for some procedures | Adequate for most restorative work |
| Hemostasis | Better local hemostasis | Less vasoconstriction |
| Systemic epi load | Higher per cartridge | Lower—prefer when CV risk moderate |
| AFK decision rule | Surgical hemostasis needs | Routine restorative with medical caution |
Levonordefrin (often 1:20,000 with mepivacaine) is primarily α-agonist with less β activity than epinephrine—still not “free” of cardiovascular effects.
Maximum epinephrine teaching ceilings (healthy vs cardiac risk) vary by guideline era; classic dental teaching often cites ~0.2 mg epi total in healthy adults and ~0.04 mg in significant cardiovascular disease (roughly 2 cartridges of 1:100,000). Use lowest effective concentration/dose, aspirate, inject slowly, and monitor.
Contraindications and Cautions for Epinephrine
| Category | Examples / rationale |
|---|---|
| Absolute / near-absolute | Uncontrolled hyperthyroidism; pheochromocytoma; cocaine or amphetamine intoxication (arrhythmia risk); sulfite allergy when only sulfite-containing epi solutions available |
| Significant cardiovascular disease | Unstable angina, recent MI, severe uncontrolled hypertension, refractory arrhythmias—limit or avoid; medical consultation; prefer plain mepivacaine when profound short block suffices |
| Drug interactions | Non-selective β-blockers (unopposed α → hypertensive response risk); TCAs (potentiate pressors—limit epi); MAOIs historically listed; digoxin/arrhythmia risk with excess catecholamines |
| Hyperthyroidism (controlled vs not) | Controlled often OK with limited epi; uncontrolled—avoid |
| Pregnancy | Lidocaine with limited epi is widely used when indicated (FDA legacy category B teaching for lidocaine); avoid unnecessary high dose; consult current guidance |
| Glaucoma (narrow-angle) | Systemic catecholamines caution in older texts—usually not a ban on dental cartridges at standard doses but know the flag |
Endogenous catecholamines from pain and anxiety often exceed the small epi dose in one carefully given cartridge—profound anesthesia itself is cardioprotective by reducing stress response. Do not withhold needed LA out of unfounded fear; withhold or limit epi when disease/drugs make exogenous catecholamines dangerous.
Methemoglobinemia
Methemoglobin (MetHb) is hemoglobin iron in the Fe³⁺ state that cannot carry oxygen well; patients appear cyanotic with chocolate-brown blood and may have low SpO₂ that responds poorly to oxygen alone until MetHb is reduced.
| Feature | Detail |
|---|---|
| Dental culprits | Prilocaine (metabolite o-toluidine), benzocaine topical (especially sprays), rarely articaine or others |
| Risk factors | High dose, infants/young children, G6PD deficiency, congenital methemoglobinemia, concurrent oxidant drugs |
| Clinical | Cyanosis, headache, fatigue, dyspnea, tachycardia; severe → lethargy, coma, death |
| Clue | Cyanosis with relatively normal PaO₂ on ABG; pulse oximetry often ~85% plateau; co-oximetry diagnoses MetHb % |
| Treatment | Stop offending agent; supportive O₂; methylene blue IV (first-line in symptomatic significant MetHb; caution in G6PD deficiency); ICU/emergency transfer |
AFK stem pattern: child after multiple benzocaine applications or adult after high-dose prilocaine develops cyanosis → think methemoglobinemia, not simple hypoxia from airway obstruction alone (though both need ABC assessment).
Choosing Agents—Integrated Clinical Rules
- Healthy adult restorative, short–moderate duration: lidocaine 2% with epi 1:100k or articaine 4% with epi 1:200k/1:100k per preference and site.
- Need long post-op soft-tissue anesthesia (e.g., surgery): bupivacaine 0.5% with epi for prolonged analgesia—warn about soft-tissue injury (lip/tongue biting), especially in children.
- Epinephrine minimization: mepivacaine 3% plain for short procedures; limit total dose carefully.
- Infected “hot” tooth: block away from infection (nerve block) rather than infiltration into abscess; consider supplemental techniques (next section).
- Hepatic failure: amides accumulate—reduce dose, simplify regimen, consider medical consult; esters theoretically extrahepatic but rarely used as injectables.
- Pseudocholinesterase deficiency: prolongs ester metabolism—avoid high-dose esters.
- Always aspirate, inject slowly, stay below MRD, document cartridges.
Rapid review list
- Amides = liver; esters = plasma; benzocaine topical ester
- Free base crosses membrane; acid tissue → failure
- pKa ↓ → onset ↑; protein binding ↑ → duration ↑
- 2% × 1.8 mL ≈ 36 mg; 4% ≈ 72 mg per cartridge
- Lidocaine/articaine ~7 mg/kg with vaso; bupivacaine ~1.3–2 mg/kg
- 1:100k = 18 μg epi/cartridge; 1:200k = 9 μg
- Limit epi in unstable CV disease, uncontrolled hyperthyroid, cocaine
- Prilocaine/benzocaine → methemoglobinemia; methylene blue
Section 13.2 applies these drugs to injection anatomy, failures, and complications including systemic toxicity stages.
Which statement best contrasts amide and ester local anesthetics used in dentistry?
A 70 kg healthy adult receives 2% lidocaine with 1:100,000 epinephrine. Approximately how many milligrams of lidocaine are in one 1.8 mL cartridge, and what is a commonly taught maximum recommended dose with epinephrine?
Compared with epinephrine 1:100,000, epinephrine 1:200,000 in a dental cartridge provides:
Which clinical scenario most strongly suggests local anesthetic–related methemoglobinemia?