DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 19–3
Some Pharmacological Effects of Parenteral Anesthetics a
DRUG CBF CMRO 2
ICP MAP HR CO RR V˙
E
Thiopental --- --- --- - + - - --
Etomidate --- --- --- 0 0 0 - -
Ketamine ++ 0 ++ + ++ + 0 0
Propofol --- --- --- -- + - -- ---
ABBREVIATIONS: CBF, cerebral blood flow; CMRO 2
, cerebral oxygen consumption; ICP, intracranial pressure; MAP, mean arterial pressure; HR, heart
rate; CO, cardiac output; RR, respiratory rate; , minute ventilation.
V˙E
a
Typical effects of a single induction dose in humans; see text for references. Qualitative scale from --- to +++ = slight, moderate, or large decrease
or increase, respectively; 0 indicates no significant change.
the inhalational anesthetics are emphasized in the following
sections.
Table 19–1 lists the widely varying physical properties
of the inhalational agents in clinical use. These
properties are important because they govern the pharmacokinetics
of the inhalational agents. Ideally, an inhalational
agent would produce a rapid induction of anesthesia
and a rapid recovery following discontinuation.
Pharmacokinetic Principles
The inhalational agents are some of the very few pharmacological
agents administered as gases. The fact that
H
F
F Br
F C C H
F Cl
Halothane
F
F
H
C C O
Isoflurane
F
C
Cl
F
H
F
C
F
H
F F F
C C O C
Cl F F
Enflurane
Desflurane
H C O C H
O
F C F F
N N
F
Sevoflurane
Nitrous Oxide
Figure 19–4. Structures of inhalational general anesthetics. Note
that all inhalational general anesthetic agents except nitrous
oxide and halothane are ethers, and that fluorine progressively
replaces other halogens in the development of the halogenated
agents. All structural differences are associated with important
differences in pharmacological properties.
H
H
F
F
H
C C O
F
F
C
F
H
H
these agents behave as gases rather than as liquids
requires that different pharmacokinetic constructs be
used in analyzing their uptake and distribution.
It is essential to understand that inhalational anesthetics
distribute between tissues (or between blood and
gas) such that equilibrium is achieved when the partial
pressure of anesthetic gas is equal in the two tissues.
When a person has breathed an inhalational anesthetic
for a sufficiently long time that all tissues are equilibrated
with the anesthetic, the partial pressure of the
anesthetic in all tissues will be equal to the partial pressure
of the anesthetic in inspired gas. Note, however,
that while the partial pressure of the anesthetic may be
equal in all tissues, the concentration of anesthetic in
each tissue will be different. Indeed, anesthetic partition
coefficients are defined as the ratio of anesthetic
concentration in two tissues when the partial pressures
of anesthetic are equal in the two tissues. Blood:gas,
brain:blood, and fat:blood partition coefficients for the
various inhalational agents are listed in Table 19–1.
These partition coefficients show that inhalational anesthetics
are more soluble in some tissues (e.g., fat) than
they are in others (e.g., blood), and that there is significant
range in the solubility of the various inhalational
agents in such tissues.
In clinical practice, one can monitor the equilibration
of a patient with anesthetic gas. Equilibrium is
achieved when the partial pressure in inspired gas is
equal to the partial pressure in end-tidal (alveolar) gas.
In other words, equilibrium is the point at which there
is no net uptake of anesthetic from the alveoli into the
blood. For inhalational agents that are not very soluble
in blood or any other tissue, equilibrium is achieved
quickly, as illustrated for nitrous oxide in Figure 19–5.
If an agent is more soluble in a tissue such as fat, equilibrium
may take many hours to reach. This occurs