Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INHALATION ANESTHETIC AGENTS
P A /P I (%)
100
A
B
A rapid fall in alveolar partial pressure is required for
a swift recovery. If significant quantities of inhalation
agent reside in the tissues at the end of anesthesia,
transport of this agent back to the alveoli will serve to
slow the fall in alveolar partial pressure and recovery
will be delayed.
0
0
Time (min)
Fig. 5.3 The rise in alveolar partial pressure of
anesthetic (P A ) towards the inspired partial pressure (P I )
for an agent of (A) low and (B) high solubility in blood.
remain within the alveoli, the alveolar partial pressure
at equilibration approaches the partial pressure of anesthetic
in the inspired gas. The result is a rapid rise in
alveolar partial pressure and therefore rapid induction
of anesthesia. In contrast, for an agent that is highly
soluble in blood (Fig. 5.3B) more anesthetic molecules
must diffuse from the alveoli into the blood before
equilibration is reached. As a result, the partial pressure
of anesthetic in the alveoli at equilibrium is very much
less than that in the inspired gas. Consequently, the rise
in alveolar partial pressure is slowed and induction
delayed.
Cardiac output
A high cardiac output tends to slow anesthetic induction.
An increase in blood flow through the lungs serves
to maintain the diffusion gradient between the alveoli
and blood. Therefore, more molecules of anesthetic
diffuse out of the alveoli, slowing the rise in alveolar
partial pressure of anesthetic. The influence of cardiac
output is evident in clinical cases. Induction is frequently
slowed in excited patients but occurs more rapidly in
animals with reduced cardiac output, e.g. in hypovolemia
or shock.
Solubility in tissues
A faster induction and recovery are associated with
anesthetic gases and vapors that are poorly soluble in
the tissues. At induction, tissue uptake lowers the venous
partial pressure of anesthetic, thereby restoring the diffusion
gradient between alveolar air and blood. In turn,
this maintains the movement of anesthetic molecules out
of the alveoli, slowing the rise in alveolar partial pressure.
For inhalation anesthetics that are relatively insoluble
in the tissues, these effects are minimal. However,
for more soluble agents, tissue uptake may considerably
reduce venous and thus alveolar partial pressures.
Metabolism and elimination
Inhalation anesthetics are eliminated primarily through
the lungs, i.e. they are exhaled. Nonetheless, these
agents are not totally inert and undergo biotransformation,
primarily in the liver, to a variable degree. Metabolism
might be expected to promote recovery from
anesthesia. However, for the newer inhalation agents
any contribution to recovery is slight. Of more direct
importance is the potential production of toxic metabolites.
The generation of such intermediates does not
require exposure to high concentrations of inhalation
agent and so this form of toxicity is a hazard to the
anesthetist (or indeed anyone working in a contaminated
environment) as well as the patient.
Anesthetic potency: minimum alveolar
concentration
The potency of a drug is a measure of the quantity of
that drug that must be administered to achieve a given
effect; the more potent the drug, the less is required. In
the case of inhalation anesthetics potency is described
by the minimum alveolar concentration (MAC). The
MAC value is the minimum alveolar concentration of
anesthetic that produces immobility in 50% of patients
exposed to a standard noxious stimulus. The lower the
MAC, the more potent the anesthetic. The MAC is
inversely correlated to the oil:gas partition coefficient.
Thus a very potent inhalation anesthetic will have a low
MAC and a high oil:gas partition coefficient.
MAC values vary slightly between species and may
also be modified by other factors such as body temperature
and age (Table 5.1). Many of the drugs included in
anesthetic protocols, including sedatives, analgesics and
injectable anesthetics, reduce the MAC of inhalation
anesthetics.
General side effects
Central nervous system effects
All inhalation anesthetics induce reversible dosedependent
depression of the CNS. However, the volatile
agents do not possess specific analgesic activity.
Most inhalation agents vasodilate the cerebral vasculature,
thereby increasing cerebral blood flow and
raising intracranial pressure. Such changes are unlikely
to be significant in normal patients. However, if
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