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!!