Donald H. Lambert
Pharmacology of Local AnestheticsPharmacology of Local Anesthetics
Nerve
Muscle
Compound action potential = sum of individual AP
Individual fibers blocked = decline in comp. AP
B + H+BH+
H+
The Local Anesthetic MoleculeThe Local Anesthetic Molecule
Local anesthetics consist of an aromatic ring and an amine, separated by a hydrocarbon chain
Two types of local anesthetics based on the hydrocarbon chain linkage
Esters have [-CO-O-] linkageAmides have [-N-CO-] linkage
Hydrophobic Hydrophilic
N C
O
O C C NCH3
CH3
H9C4
NH2 C
O
O C C N
C2H5
C2H5
NH2 C
O
O C C N
Cl
C2H5
C2H5
Procaine
Chloroprocaine
Tetracaine
ESTERS
N
O
NH
CH3
CH3 CH3
H
N
O
NH
CH3
CH3 CH2
CH2
CH2
CH3
H
M epivacaine
Ropivacaine
Bupivacaine
N
O
NH
CH3
CH3 CH2
CH2
CH3
HHAmide
Bupivacaine Analogues
AmideLidocaineAnalogues
Amides v. EstersAmides v. Esters
Parameter Amides Esters
Stability
Metabolism
Allergy
Stable Unstable
Liver/kidney Plasma
Rare Less rare
AGENTS OF LOW POTENCYAGENTS OF LOW POTENCYAND SHORT DURATIONAND SHORT DURATION
AGENT CHEMICAL RELATIVE ONSET DURATION CLASS POTENCY (MINUTES)
PROCAINE ESTER 1 SLOW 60 - 90
CHLOROPROCAINE ESTER 1 FAST 30 - 60
AGENTS OF INTERMEDIATEAGENTS OF INTERMEDIATEPOTENCY AND DURATIONPOTENCY AND DURATION
AGENT CHEMICAL RELATIVE ONSET DURATION CLASS POTENCY (MINUTES)
LIDOCAINE AMIDE 2 FAST 90 -200
MEPIVACAINE AMIDE 2 FAST 120 - 240
PRILOCAINE AMIDE 2 FAST 120 - 240
AGENTS OF HIGH POTENCYAGENTS OF HIGH POTENCYAND LONG DURATIONAND LONG DURATION
AGENT CHEMICALCLASS
RELATIVEPOTENCY
ONSET DURATION(MIN)
ROPIVACAINE AMIDE 4 INTERMED. 180-600
TETRACAINE ESTER 6 SLOW 180-600
BUPIVACAINE AMIDE 6 INTERMED. 180-600
LEVOBUPIV. AMIDE 6 INTERMED. 180-600
ETIDOCAINE AMIDE 6 FAST 180-600
Lipid Solubility = Potency Lipid Solubility = Potency (and Duration)(and Duration)
Lipid Bi-layer
Protein Binding = DurationProtein Binding = Duration
Lipid Bi-layer
Protein Na+Channel
pKa = ONSET
Effect of Dose on Onset, Duration, and Quality of Effect of Dose on Onset, Duration, and Quality of AnesthesiaAnesthesia
• As dose increases
•The more you inject thefaster it comes on, the betterthe block, the longer itlasts, and the greater the toxicity
• Onset time decreases from 12 min. to 5 min.
• Adequacy increases from 40% to 100%
• Duration increases from 100 to 260 min.
Neuron Types
Factors Influencing Local Anesthesia
pH of local anesthetic Pregnancy Site of injection
Adding sodium bicarbonate raises the pH of the local anesthetic solution
????
Median Nerve Block in Pregnant and Non-Pregnat WomenMedian Nerve Block in Pregnant and Non-Pregnat Women
0
10
20
30
40
50
60
70
80
90
100R
edu
ctio
n in
Act
ion
Po
ten
tial
A
mp
litu
de
(% o
f co
ntr
ol)
0 5 10 15 20
Minutes after injection
Preg
Non-Preg
J Butterworth, et al. Anesthesiology 1990;72:962-5
Collection of data of local anesthetic blood levels (mainly plasma concentrations) from various sources indicating the pattern of order of peak concentrations associated with various regional anesthetic blocks.
Rosenberg PH, Veering BT, Urmey WF: Reg Anesth Pain Med 2004; 29: 564-75
Intercostal > caudal > epidural > brachial plexus > subcutaneous
The Pharmacology of Local Anesthetics
Important stuff for everyday practice!
And for exams!!