Chapter 4
- Mechanisms of Action
- Donald D. Koblin
Although currently popular inhaled anesthetics include nitroux
oxide and the halogenated ethers isoflurane and sevoflurane, a far greater variety
of inhaled agents can produce anesthesia ( Fig.
4-1
). The properties of these anesthetics vary considerably. For example,
cyclopropane and diethyl ether are no longer used because of their explosiveness
and flammability. Halothane is nonflammable but possesses a permanent dipole moment,
can form hydrogen bonds, and is metabolized by the liver. Xenon, an anesthetic more
potent than nitrous oxide in humans,[1]
is essentially
inert and undergoes no known transformation in the body.
The structural diversity of inhaled anesthetics suggests that
they all do not interact directly with a single, specific receptor site. However,
attempts to find a common (unitary) mechanism of general naesthetic action have
Figure 4-1
Chemical structures of various inhaled anesthetics.
A, Anesthetics in current clinical use. B,
Anesthetics in previous clinical use. C, Some experimental
anesthetics. Anesthetics with asymmetric carbon atoms (asterisks)
are mixtures of the optical isomers.
sought correlations of the potencies of anesthetics with their physicochemical properties.
An example is the striking, albeit imperfect, relationship between anesthetic potency
and lipid solubility (see "Physicochemical Nature of the Site of Anesthetic Action").
Although such correlations do not provide a detailed mechanism of anesthesia, they
have been helpful in defining the environment in which anesthetics act.
Any molecular hypothesis of anesthesia must explain the effects
of anesthetics on the whole organism. For instance, because anesthetic administration
can rapidly induce unconsciousness and because awakening can occur quickly after
the discontinuation of anesthesia, physical or biochemical changes important to the
mechanism of anesthesia must occur within seconds. Similarly, physical or biochemical
alterations caused by anesthetics are meaningful only at clinical concentrations
and physiologic temperatures and not at high anesthetic levels.[2]
High levels may produce toxic effects unrelated to the mechanism by which inhaled
anesthetics act. The anesthetic requirement does not change or decreases only slightly
with increasing duration of anesthesia.[3]
Any
physical or biochemical change causally related to the anesthetic state should be
stable while an organism is anesthetized and should disappear on emergence from anesthesia.
The mechanisms by which inhaled anesthetics act may overlap the
mechanisms of action of intravenous anesthetics (see Chapter
10
and Chapter 11
),
local anesthetics (see Chapter 14
),
and even of alcohols.[4]
This chapter considers
only the inhaled agents.
