Pharmacology of Local Anesthetics in Dentistry
Outline 1. 2. 3. 4. 5. 6.
Brieff Intr Brie Introd oduc ucti tion on and and st stru ruct ctur ure e Dent De ntal al Lo Loca call Ane Anest sthe heti tic c Dru Drugs gs Vaso Va soco cons nstr tric icto tors rs an and d ot othe herr ad addi diti tive ves s Topica call An Anesth the etics Dose Ca Calculations Relative Analgesi sia a
Brief Introduction All Local Anesthetics are: ● ● ●
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Weak Bases Unstable Have Have an acid acidic ic pH to maxi maximi mise se thei theirr wat water er solubility and chemical stability - increases shelf-life Poor Poorly ly wate waterr sol solub uble le in un-i un-ion onize ized d sta state te Have Have lipo lipoph phil ilic ic and and hydr hydrop ophi hili lic c ends ends Funct Functio iona nall char charact acter eris istic tics s dete determ rmin ined ed by by the dissociation constant (pKa ), ) , lipid solubility, solubility, and protein binding
Structure R3NH + HCl -> R3NH+ + Cl-
Functional Characteristics 1.
Dissociation constant (pKa ): How easy ions dissociate
The closer the LA’s pKa to the body’s pH, the faster the onset Most local anesthetics have a pKa greater than 7.4. Because the neutral base form of the local anesthetic (R 3N) is more lipophilic, can penetrate nerve membranes faster. As the pKa of a local anesthetic rises, rises , the percentage in the ionized form (R3NH+) increases and onset of the block slows 2. 3.
Lipid solubility Protein binding. binding.
Functional Characteristics 1. 2.
Dissociation constant (pKa) Lipid solubility
Solubility
Ability to penetrate connective tissue and cell membranes
Potency 3.
Protein binding
Affinity for protein binding Duration of action
Time bound to nerve membranes
Types of LA’s used in Dentistry
We usually use: 1.Xylestesin A (2% lidocaine hydrochloride, adrenaline 1:80.000) 2. Mepivastesin (3% Mepivacaine)
Vasoconstrictors ● ●
Reduce bloo Reduce blood d flow flow at site site of inj inject ection ion,, reduc reducing ing the the sprea spread d of LA, LA, hence hence increasing duration Delays Del ays the the abso absorpt rption ion whi which ch decr decreas eases es chan chance ce of of system systemic ic toxici toxicity ty
Two types are used 1. 2.
Adrenaline: Effective vasoconstrictor, Contraindication: Heart Disease Felypressin: Less effective, slower onset, minimal effect on the heart
Other Additives 1. 2. 3. 4.
Preservat Preser vative ive:: Prev Prevent ent oxi oxidat dation ion of vas vasoco oconst nstric rictor tor Bicarbo Bica rbonat nate: e: Spee Speed d of of onset onset of anae anaesthe sthesia sia is incr increas eased ed Opio Op ioid ids: s: Enh Enhan ance ce and and pr prol olon ong g LA’ LA’s s effe effect ct Gluc Gl ucos ose: e: To in incr crea ease se ba bari rici city ty
Alkalinisation -
To be adde added d imm immed edia iate tely ly befo before re injection May May res resul ultt in in les less s sti sting ngin ing g pai pain n bei being ng experienced by the patient More More rapi rapid d dru drug g dif diffu fusi sion on and and a quick quicker er onset of nerve blocking Has Has to be adde added d care carefu full lly y - pre preci cipi pita tati tion on
Routes of Uptake 1) ➢
2) ➢
3) ➢ ➢
Oral route Hepatic first pass effect (72% lignocaine) Topica Top icall (Can (Can be use used d in in case case of of probl problem em stat stateme ement) nt) Mucosa 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) 2) 3) 4) 5) 6)
Benzocaine Dyclonine Lidocaine Tetracaine Buta Bu tamb mben en (ON ONLY LY in in mix mixtu turre) 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
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 (V d) ➢ ➢
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 V d / 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 s olution 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 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 ➢
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Clark’s Rule Weight Divid Di vided ed by 150 150 → Fr Frac acti tion on of of adul adultt dose dose to to chil child d Simi Si mila larr to to wei weigh ghtt x MRD MRD for for ch chil ildr dren en 2 x 15 150 0 x (5 (50 0 / 15 150) 0) = 10 100m 0mg g OR 2 x 50 = 10 100m 0mg g Young’s Rule Age Adul Ad ultt dosa dosage ge x ch chilild’ d’s s age age / (12 (12 + ch chilild’ d’s s age) 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 ➢
1) 2) 3) 4) ➢ ➢ ➢ ➢
Four levels Tingli Tin gling ng sen sensat sation ion / feel feeling ing of vibr vibrati ation on (6(6-25% 25%)) Warm Wa rm sen sensat satio ion n / fee feelin ling g of dr drun unk k (25(25-45 45%) %) Loss Lo ss of ab abililit ity y to to re resp spon ond d (4 (466-65 65%) %) Slee Sl eepi pine ness ss / “dr “drea eam” m” (6 (666-80 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 ➢
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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 ➢
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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
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