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

General Anesthetics and
Therapeutic Gases
Piyush M. Patel, Hemal H. Patel,
and David M. Roth
General Anesthetics
General anesthetics depress the central nervous system
to a sufficient degree to permit the performance of surgery
and other noxious or unpleasant procedures.
Inevitably, anesthetics also suppress normal homeostatic
reflexes. Not surprisingly, general anesthetics have
low therapeutic indices and thus require great care in
administration. While all general anesthetics produce a
relatively similar anesthetic state, they are quite dissimilar
in their secondary actions (side effects) on other
organ systems. The selection of specific drugs and
routes of administration to produce general anesthesia
is based on their pharmacokinetic properties and on the
secondary effects of the various drugs, in the context of
the proposed diagnostic or surgical procedure and with
the consideration of the individual patient’s age, associated
medical condition, and medication use.
Anesthesiologists also employ sedatives (Chapter 17),
neuromuscular blocking agents (Chapter 11), and local
anesthetics (Chapter 20) as the situation requires.
Historical Perspectives. Crawford Long, a physician in rural
Georgia, first used ether anesthesia in 1842. William T.G. Morton,
a Boston dentist and medical student, performed the first public
demonstration of general anesthesia using diethyl ether in 1846
when Gilbert Abbott underwent surgical excision of a neck tumor
at the Massachusetts General Hospital in the operating room now
known as “the ether dome.” The era of modern anesthesia and a
revolution in the medical care of the surgical patient had begun.
Ether was the ideal “first” anesthetic. A liquid at room temperature,
it readily vaporized, and was easy to administer. Ether,
unlike nitrous oxide, was potent and could produce anesthesia without
diluting room air to hypoxic levels. It was relatively nontoxic
and produced limited respiratory or circulatory compromise. Ether
maintained a role in clinical anesthesia until the 1950s.
Horace Wells, a dentist, noted at a stage show that an
injured participant under the influence of nitrous oxide felt no
pain. The next day Wells had a tooth extracted while breathing
nitrous oxide. An attempt in 1845 by Wells to demonstrate his discovery
at the Massachusetts General Hospital in Boston ended in
failure when the patient cried out and nitrous oxide fell into disuse.
In 1868, Edmond Andrews, a Chicago surgeon, described the
co-administration of nitrous oxide and oxygen, a practice that continues
to this day.
The Scottish obstetrician James Simpson introduced chloroform
in 1847. Chloroform had a more pleasant odor than ether
and was nonflammable. It was, however, a hepatotoxin and a
severe cardiovascular depressant, which limited its ultimate utility.
Despite incidents of intraoperative and postoperative deaths
associated with chloroform, its use continued, especially in Great
Britain, for nearly 100 years.
The anesthetic properties of cyclopropane were discovered
accidentally in 1929 by chemists analyzing impurities in propylene.
Cyclopropane is a pleasant-smelling gas that produces rapid anesthetic
induction and recovery, and was widely used as a general anesthetic
for over 30 years. However, cyclopropane is explosive when
mixed with air, oxygen, or nitrous oxide. In 1956 came the introduction
of halothane, a nonflammable volatile halogenated alkane that
quickly became the dominant anesthetic.
In 1935, Lundy demonstrated the clinical usefulness of
thiopental, a rapidly acting agent that could be administered intravenously;
however, anesthetic doses of thiopental resulted in serious
depression of the circulatory, respiratory, and nervous systems.
The further development of intravenous anesthetic agents such as
propofol, combined with other intravenous anesthetic adjuncts such
as midazolam, dexmedetomidine, and remifentanil, has led to the
use of total intravenous anesthesia (TIVA) as a clinically useful tool
in modern anesthetic practice.
GENERAL PRINCIPLES OF SURGICAL
ANESTHESIA
Unlike the practice of every other branch of medicine,
anesthesia is usually neither therapeutic nor diagnostic.
The exceptions to this, such as treatment of status