Pharmacology of Local Anesthetics

in Dentistry
Outline
1. Brief Introduction and structure
2. Dental Local Anesthetic Drugs
3. Vasoconstrictors and other additives
4. Topical Anesthetics
5. Dose Calculations
6. Relative Analgesia
Brief Introduction
All Local Anesthetics are:

Weak Bases
Unstable
Have an acidic pH to maximise their water
solubility and chemical stability - increases
shelf-life
Poorly water soluble in un-ionized state
Have lipophilic and hydrophilic ends
Functional characteristics determined by the
dissociation constant (pKa ), lipid
solubility, and protein binding.
 Structure

R3NH + HCl -> R3NH+ + Cl-

Functional Characteristics
1. Dissociation constant (pKa ): How easy ions dissociate

The closer the LAs pKa to the bodys pH, the faster the onset

Most local anesthetics have a pKa greater than 7.4. Because the neutral base
form of the local anesthetic (R3N) is more lipophilic, can penetrate nerve
membranes faster. As the pKa of a local anesthetic rises, the percentage in the
ionized form (R3NH+) increases and onset of the block slows

2. Lipid solubility
3. Protein binding.
Functional Characteristics
1. Dissociation constant (pKa)
2. Lipid solubility

Solubility Ability to penetrate connective tissue and cell membranes

Potency

3. Protein binding

Affinity for protein binding Time bound to nerve membranes

Duration of action
Types of LAs used in Dentistry We usually use:

1.Xylestesin A (2% lidocaine

hydrochloride, adrenaline 1:80.000)
2. Mepivastesin (3% Mepivacaine)
Vasoconstrictors
Reduce blood flow at site of injection, reducing the spread of LA, hence
increasing duration
Delays the absorption which decreases chance of systemic toxicity

Two types are used

1. Adrenaline: Effective vasoconstrictor, Contraindication: Heart Disease

2. Felypressin: Less effective, slower onset, minimal effect on the heart
Other Additives
1. Preservative: Prevent oxidation of vasoconstrictor
2. Bicarbonate: Speed of onset of anaesthesia is increased
3. Opioids: Enhance and prolong LAs effect
4. Glucose: To increase baricity
Alkalinisation
- To be added immediately before
injection
- May result in less stinging pain being
experienced by the patient
- More rapid drug diffusion and a quicker
onset of nerve blocking
- Has to be added carefully - precipitation
Routes of Uptake
1) Oral route
Hepatic first pass effect (72% lignocaine)
2) Topical (Can be used in case of problem statement)
Mucosa
3) Injection
Vascularity of target site
Vasoactivity of drug
Topical Anesthetics
Potentially more toxic than injectable LA
Inadequate methods for determining doses (esp. Liquid, gel, unmetered
sprays)
Penetrates the mucous membrane / tissue Superficial nerves
Depth: 2-3mm
Reduce pain of injection (except ID block)
Esp. max. lingual injection medial to 1st molar
Topical Anesthetics
Common forms
Liquid rinses Less site-specific
Gels Useful in smaller areas Cotton swabs
Metered / unmetered sprays
Application of refrigerant Faster
Oral cavity patches
Subgingival liquid-to-gel system Cartridge form Easy quantified volume
etc
Common Topical Agents
1) Benzocaine
2) Dyclonine
3) Lidocaine
4) Tetracaine
5) Butamben (ONLY in mixture)
6) Eutectic mixture
Common Topical Agents
Lidocaine

5% ointment, gel, liquid

10% metered spray
Onset: 1-2min

Benzocaine

14-20% liquid, gel

Onset: 30s
Lower toxicity
Recommended for pedo
May induce methemoglobinemia
Common Topical Agents
Dyclonine

Dyclonine hydrochloride
Ketone
Safe, durable
Bactericidal & fungicidal
Dose Calculations (Recap)
Bioavailability (F)

Extent of absorption
For i.v. injection F=1
F = AUC x CL / Dose

Volume of Distribution (Vd)

Apparent volume distributed by drug

Vd = Dose / Ct
Dose Calculations (Recap)
Half-life (t1/2)

Time taken for [drug] in plasma to be reduced by half

t1/2 = ln2 / k

Drug Clearance (CL)

Efficiency of drug removal

CL = Vd x k
Dose Calculations (Recap)
Loading Dose

Dose(s) given at the onset to achieve target conc. rapidly

Loading dose = Target Cp x Vd / F

Maintenance Dose

Drug administration to maintain steady-state conc.

Dosing rate = Target Cp x CL / F
Dose Calculations
Other necessary information

Concentration for anesthetic drug

Standard cartridge volumes
Dilution percentages for vasoconstrictors
Defined MRD
Dose Calculations
Drug Concentration

Drug percentage (Relative amount in cartridge)

No. of grams in 100mL of solution
100% = 1000mg / mL
10% = 100mg / mL
Dose Calculations
Dose Calculations
Case: 1% lidocaine, 1.7mL / cart

For healthy adult, MRD = 3.2mg/lbs or 7mg/kg

Maximum recommended dose = 7 x weight in kg

Maximum no. of cart = 7 x weight / (10 x 1.7)

Dose Calculations
Standard North American cartridge = 1.8 mL (1.8 cc)
1 cartridge of 1 % LA = 10mg/mL x 1.8mL/cart = 18mg/cart
Sometimes: 1.7 mL / others

Example: Two cartridges of 2% lidocaine administered to 100-lb patient

Drug administered = 2 (cartridges) x 36mg = 72mg

MRD = 3.2mg/lb x 100lb = 320mg

Additional dose = 320 - 72 = 248mg

No. of additional cartridge = 248 / 36 = 6.8 cart

Dose Calculations
Vasoconstrictor dose

Dilution ratios
MRD is NOT dependent of weight
Expressed as mg/mL(or cc)
Example

1:1,000 = 1g / 1000mL = 1mg / 1mL

In standard cartridge 1.8mg / cart

1:20,000 / 1:50,000 / 1:100,000 / 1:200,000

Dose Calculations
Limiting drug

Example: 2% lidocaine, 1:100,000 epinephrine administered to patient of 150lbs

Max. (lidocaine) = 3.2 x 150 = 480mg = ~13 cart

Max. (epinephrine) = 0.2 / 0.018 = ~11 cart

In this case Epinephrine is limiting drug

Cardiac dose

0.04mg for epinephrine & 0.2mg for levonordefrin

Dose Calculations
Paediatric doses

Example: 2% lidocaine for 50-lb child, MRD = 2mg/lb

Clarks Rule
Weight
Divided by 150 Fraction of adult dose to child
Similar to weight x MRD for children
2 x 150 x (50 / 150) = 100mg OR 2 x 50 = 100mg
Youngs Rule
Age
Adult dosage x childs age / (12 + childs age)
300 x 6 / (12 + 6) = 100mg
Relative Analgesia (RA)
Drug administration Reduce pain perception
Inhalation sedation / laughing gas / nitrous oxide-oxygen
Conscious but may have loss of memory of treatment
Nitrous oxide
Rapid saturation (5min) & elimination (90% in 10min)
Subject in problem statement
Relative Analgesia
Four levels
1) Tingling sensation / feeling of vibration (6-25%)
2) Warm sensation / feeling of drunk (25-45%)
3) Loss of ability to respond (46-65%)
4) Sleepiness / dream (66-80%)
Light / non-fatty meal
Increment of 10% nitrous oxide / 1min (NOT exceeding 50%)
Desired mix is fed through tube to nasal hood Breathing
Double-mask
Relative Analgesia
Adv

Works rapidly Reaches brain within 20s, relaxation & pain-killing after 2 or
3 min
Depth of sedation can be adjusted from time to time
Varying duration of action
No hangover Rapid elimination
No injection
Few side effects
Relative Analgesia
Disadv

NOT suitable for patients with airway problems / chemotherapy / pregnant

women
NOT enough sedation for some with permissible oxygen level
NOT common in many dental clinics
Trained staff / bulky & costly equipment
Possible health risks
END