Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INHALATION ANESTHETIC AGENTS
Pharmacokinetics
Chemical and physical properties
Isoflurane is a halogenated ether (see Fig. 5.1). It is a
nonflammable and stable anesthetic vapor. It is not
degraded by ultraviolet light and the inclusion of
preservatives is unnecessary.
Solubility
Isoflurane has a lower blood:gas partition coefficient
than halothane (see Table 5.2) and is therefore associated
with a more rapid induction, recovery and rate of
change of anesthetic depth. The oil:gas partition coefficient
is also lower and this reflects the lower potency
and higher MAC of isoflurane (≈1.3% in the dog). Solubility
in tissues such as fat is slightly less than for
halothane.
Metabolism and elimination
In people, the rate of metabolism of isoflurane is
extremely low, less than 0.2%, and virtually all the
isoflurane inhaled is exhaled unchanged. What metabolism
there is occurs in the liver and the main products
are trifluoroacetic acid and inorganic fluoride ions.
Adverse effects
Central nervous system effects
Isoflurane produces less cerebral vasodilation than
halothane, while still reducing metabolic oxygen consumption.
The reduced oxygen requirement is usually
sufficient to compensate for any tendency towards
impaired oxygen delivery. Thus, isoflurane is preferred
over halothane when anesthetizing patients with elevated
intracranial pressure. Furthermore, isoflurane,
unlike halothane, does not impair the responsiveness of
the cerebral circulation to carbon dioxide and hyperventilation
can be used to lower intracranial pressure in
isoflurane-anesthetized patients.
Cardiovascular effects
Isoflurane does depress myocardial contractility, but to
a lesser degree than halothane. Heart rate tends to
increase slightly so that at light-to-moderate levels of
anesthesia, cardiac output is often maintained. Isoflurane,
like halothane, frequently causes arterial blood
pressure to fall. However, decreased vascular resistance,
rather than reduced cardiac output, is the main mechanism
involved.
As a halogenated ether, isoflurane is associated with
a much lower incidence of arrhythmias than
halothane.
Respiratory effects
Isoflurane depresses ventilation to a greater extent than
halothane; therefore arterial partial pressure of carbon
dioxide is likely to rise. Bronchodilation is a potentially
beneficial side effect.
Hepatic effects
Although isoflurane decreases hepatic portal vein blood
flow, hepatic arterial blood flow is increased. The overall
effect is a reduction in hepatic blood flow of lesser
magnitude than that seen with halothane. Consequently
hepatic injury related to hepatocyte hypoxia is less likely
to occur. Trifluoroacetic acid is a potential metabolite
of isoflurane and a condition similar to halothane
hepatitis has been reported in humans, although the
incidence is extremely low.
Renal effects
Metabolism of isoflurane is minimal; therefore very little
fluoride is generated and renal toxicity is unlikely. As
for halothane, renal blood flow and glomerular filtration
rate may be reduced.
Skeletal muscle effects
Isoflurane can trigger malignant hyperthermia in susceptible
individuals. It produces good muscle relaxation
and may maintain better muscle blood flow than
halothane.
Contraindications and precautions
Absolute contraindications are few:
● patients susceptible to malignant hyperthermia.
Known drug interactions
Isoflurane potentiates nondepolarizing neuromuscular
blocking drugs to a greater extent than halothane.
Sevoflurane
Clinical applications
Sevoflurane is a recently introduced agent that is gaining
popularity in veterinary anesthesia. It has many features
in common with isoflurane but is less potent. Unlike
isoflurane, it lacks a pungent odor and is said to be
pleasant to inhale, rendering it suitable for mask
induction.
Pharmacokinetics
Chemical and physical properties
Sevoflurane is a halogenated ether (see Fig. 5.1). It is
stable and nonflammable.
Sevoflurane reacts with the alkaline carbon dioxide
absorbents commonly used in rebreathing anesthetic
systems to yield a potentially toxic product, compound
A (CF 2 =C[CF 3 ]−O−CH 2 F). A variety of factors can
influence the generation of compound A and production
appears to be increased by:
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