Chemistry Reference
In-Depth Information
the possibility and extent of drug absorption. An example of drug action
that can be adequately explained by the pH partition hypothesis, is the
mechanism(s) of action of local anaesthetic drugs. Local anaesthetics are
drugs that are used to induce a state of temporary analgesia, or freedom
from pain. They achieve this by blocking the conduction of impulses along
nerve fibres responsible for the transmission of painful stimuli from a site of
an injury to the brain and CNS.
Local anaesthetics are basic drugs, all derived originally from cocaine
(see Figure 2.8), an alkaloid obtained from the leaves of
Erythroxylum coca
,
a small shrub which grows wild in the Andes region of South America.
Cocaine is a very effective local anaesthetic, but due to a profound stimu-
lant action on the CNS it has been replaced in most routine procedures with
synthetic, non-addictive, analogues such as lidocaine (lignocaine), prilo-
caine, procaine, etc. These drugs are aliphatic amines, with p
K
a
values for
their conjugate acids of approximately 8-9. Applying the 'rule of thumb'
shows that local anaesthetics will exist approximately 99% ionised at blood
pH (7.4).
O
CH
3
H
C
OCH
3
N
Cocaine
O
C
H
O
CH
3
H
N
C
2
H
5
C
N
Lidocaine (lignocaine)
C
2
H
5
O
CH
3
C
4
H
9
CH
3
H
H
N
N
Bupivacaine
C
O
CH
3
Figure 2.8
The structures of cocaine, lidocaine (lignocaine) and bupivacaine.
