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Chapter 16: General Anesthetics
Case Study 1
A young male patient, BO, will undergo surgery to repair torn ligaments in his left knee.
The knee injury was the result of a rough game of intramural “touch football” as part of
the fraternity competition at his university. BO is a friend of yours, and he asks you about
the general anesthesia he will experience. Of course, this is the purview of the
anesthesiologist, but you take this opportunity to give good advice to a friend. The
general anesthetics available at your hospital are structures 1–4. BO is in good health
except for his mild asthma that he treats with theophylline, 100 mg BID (structure 5).
You know the surgeon would want to have a rapid induction of anesthesia and a quick
recovery back to consciousness for this type of surgery.
1. Identify the therapeutic problem(s) where the pharmacist's intervention may
benefit the patient.
BO will have knee surgery and will undergo general anesthesia. No pre-induction
drugs are needed and no skeletal muscle relaxants are required. The surgeon
wants rapid induction/recovery general anesthesia to minimize BO’s side effects
and to quicken his postoperative recovery time.
2. Identify and prioritize the patient specific factors that must be considered to
achieve the desired therapeutic outcomes.
BO has mild asthma that is treated with theophylline.
3. Conduct a thorough and mechanistically oriented structure-activity analysis of all
therapeutic alternatives provided in the case.
Compound 1 is halothane. It is a halogenated ethane and the only useful
halogenated hydrocarbon general anesthetic. It has a blood/gas coefficient of 2.30
and a MAC of 0.77. It has a rapid onset/recovery when used alone or with nitrous
oxide. It is subject to spontaneous oxidation to HCl, HBr, and phosgene and is,
therefore, stabilized with thymol and dispensed in amber bottles. Twenty percent
of the administered dose is metabolized to oxalic acid and hydroxyacetic acid,
which accounts for its hepatotoxicity.
Compound 2 is enflurane. It is a halogenated methyl ethyl ether with a blood/gas
coefficient of 1.19 and a MAC of 1.70. Therefore, it is less soluble in blood and
less potent as compared to halothane. It is pharmacologically similar to halothane
having rapid onset/recovery but may have less nausea, vomiting, arrhythmias, and
postoperative shivering than is observed with halothane. Two percent of the
administered dose is metabolized to fluoride ion and fluoromethoxydifluoroacetic
acid, which can be nephrotoxic.
Compound 3 is methoxyflurane. It is also a halogenated methyl ethyl ether and
can be considered an analog of enflurane. It has a blood/gas coefficient of 12 and
a MAC of 0.16. Therefore, it has a high solubility in blood and is the most potent
of the halogenated anesthetics in this case. It has slow onset/recovery and 50% of
the administered dose is metabolized. Like halothane, it is metabolized to oxalic
acid and, therefore, would be expected to be nephrotoxic and hepatotoxic.
Compound 4 is nitrous oxide. It is also know as “laughing gas” and has a
blood/gas coefficient of 0.47 and a MAC of 104. It has the lowest potency and the
lowest solubility in blood of the anesthetics presented in this case. It would have
the shortest onset/recovery time and be the least potent.
4. Evaluate the SAR findings against the patient specific factors and desired
therapeutic outcomes and make a therapeutic decision.
Compound 3 (methoxyflurane) would be the least likely anesthetic to be used in
this case. It’s slow onset and recovery and its high rate of metabolism to toxic
products make it undesirable.
Halothane and enflurane both have the requisite rapid onset/recovery with low
incidence of hepatotoxicity. However, halothane would be contraindicated in this
case because BO is on theophylline, which has been shown to cause ventricular
arrhythmias when co-administered with halothane. The mechanism of this is
unknown. On the other hand, enflurane can be used with patients taking
theophylline and would be the best choice in this case.
Nitrous oxide is too weak to use by itself; however, it can be combined with the
enflurane thereby reducing the dose of each and minimizing any postoperative
side effects. The MAC for enflurane can be reduced from 1.7 to 0.60 when
combined with 70% nitrous oxide.
5. Counsel your patient.
Tell BO to divulge all medications to his physicians, especially if he is taking
herbals because of possible anesthetic herb interactions.
Assure BO that onset of general anesthesia will be fairly quick, between 5 and 10
minutes depending on the actual anesthetic used.
BO will be groggy and may experience significant nausea and vomiting as well as
some postoperative chills.
BO will also most likely be prescribed pain medication and possibly
anticoagulants as well as antibiotics, to help him through the healing process.