Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 5 ANESTHETIC AGENTS
However, beyond a certain size, additional increases in
chain length decrease potency despite further increases
in lipid solubility.
These problems with the volume expansion hypothesis
lend support to the protein theory of anesthesia,
which has gained widespread acceptance in recent years.
According to this theory, anesthetic agents interact with
protein targets to modify central synaptic transmission.
Clinically relevant concentrations of many anesthetics
have been shown to modify the activity of ion channels
and receptor proteins. Both pre- and postsynaptic effects
have been identified.
Many anesthetics have been shown to reduce presynaptic
neurotransmitter release, largely through inhibition
of voltage-gated calcium channels, while postsynaptic
effects include depression of excitatory neurotransmission
or potentiation of inhibitory neurotransmission.
The main inhibitory neurotransmitter in the brain is
γ-aminobutyric acid, or GABA. Two types of GABA
receptor have been identified: GABA A receptors, which
open chloride channels, and GABA B receptors, which
are linked to potassium channels. GABA B receptors are
largely unaffected by general anesthetic agents. However,
enhanced activation of GABA A receptors appears to be
a mechanism common to many anesthetics, including
both injectable and volatile agents.
Br F
F CI F
H C C F F C C O C H
CI F
F H F
Halothane
Isoflurane
CI F H
H C C O C
CI F H
Methoxyflurane
H
F H
H F C C O
F F
Desflurane
F
F C F
F
C H
F
F C O C H
H F C F
F
Sevoflurane
Fig. 5.1 Chemical structure of the volatile anesthetics.
INHALATION ANESTHETIC AGENTS
EXAMPLES
Halothane, isoflurane, desflurane, sevoflurane,
methoxyflurane, nitrous oxide
General chemical structure
The majority of inhalation anesthetics in common use
are halogenated organic substances, either hydrocarbons
or ethers (Fig. 5.1). In general terms, halogenation
has been shown to increase anesthetic potency while
improving stability. Nitrous oxide is an example of an
inorganic inhalation anesthetic.
General physical properties
Inhalation anesthetics can be classed as either vapors or
gases. According to this classification a gas exists in the
gaseous state at room temperature and sea-level pressure,
while a vapor exists as a liquid under similar
standard conditions. The most commonly used inhalation
agents are vapors which must therefore be converted
to the gaseous phase before addition to the carrier
gas. These agents are frequently described as the volatile
anesthetics. Nitrous oxide is one of the few anesthetic
gases in clinical use.
There are several different ways of quantifying the
amount of anesthetic vapor or gas in a mixture:
● concentration (volume %)
● partial pressure (mmHg)
● mass (mg or g).
In clinical practice concentrations of inhalation agents
are frequently quoted since vaporizers are calibrated
to deliver anesthetic as a percentage of total gas flow.
Anesthetic agent analyzers used in monitoring tend also
to use concentrations.
A vapor or gas can also be described in terms of the
partial pressure it exerts. Pressure originates when randomly
moving molecules of gas or vapor collide with
other molecules or with the walls of the container. In a
mixture of gases, the pressure exerted by an individual
vapor or gas is termed its partial pressure. A difference
in partial pressure is required if molecules of gas or
vapor are to diffuse between compartments or phases,
e.g. from alveolar air to blood. Less commonly, anesthetic
gases or vapors are quantified as mass. It is possible
to convert from mass to volume since a mole of
any gas (i.e. a gram molecular weight) will occupy a
volume of 22.4 L under standard conditions.
Vapor pressure
Molecules of liquid and gas are in constant random
motion. At a liquid–gas interface some molecules will
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