Page 462 - Basic _ Clinical Pharmacology ( PDFDrive )

448 SECTION V Drugs That Act in the Central Nervous System

anxious patients, administration of epinephrine-containing local effects are minor compared with the stress of surgery itself and
anesthetics, inadequate intraoperative anesthesia or analgesia, usually reversible after discontinuation of the anesthetic.
patients with pheochromocytomas). This effect is less marked for
isoflurane, sevoflurane, and desflurane. E. Hepatic Effects
Volatile anesthetics cause a concentration-dependent decrease
C. Respiratory Effects in portal vein blood flow that parallels the decline in cardiac
All volatile anesthetics possess varying degrees of bronchodilat- output produced by these agents. However, total hepatic blood
ing properties, an effect of value in patients with active wheezing flow may be relatively preserved as hepatic artery blood flow
and in status asthmaticus. However, airway irritation, which may to the liver may increase or stay the same. Although transient
provoke coughing or breath-holding, is induced by the pun- changes in liver function tests may occur following exposure to
gency of some volatile anesthetics. The pungency of isoflurane volatile anesthetics, persistent elevation in liver enzymes is rare
and desflurane makes these agents less suitable for induction of except following repeated exposures to halothane (see Toxicity of
anesthesia in patients with active bronchospasm. These reactions Anesthetic Agents).
rarely occur with halothane and sevoflurane, which are considered
nonpungent. Therefore, the bronchodilating action of halothane F. Effects on Uterine Smooth Muscle
and sevoflurane makes them the agents of choice in patients with Nitrous oxide appears to have little effect on uterine musculature.
underlying airway problems. Nitrous oxide is also nonpungent However, the halogenated anesthetics are potent uterine muscle
and can facilitate inhalational induction of anesthesia in a patient relaxants and produce this effect in a concentration-dependent
with bronchospasm. fashion. This pharmacologic effect can be helpful when profound
The control of breathing is significantly affected by inhaled uterine relaxation is required for intrauterine fetal manipulation or
anesthetics. With the exception of nitrous oxide, all inhaled anes- manual extraction of a retained placenta during delivery. However,
thetics in current use cause a dose-dependent decrease in tidal it can also lead to increased uterine bleeding after delivery when
volume and an increase in respiratory rate, resulting in a rapid, uterine contraction is desired.
shallow breathing pattern. However, the increase in respiratory
rate varies among agents and does not fully compensate for the
decrease in tidal volume, resulting in a decrease in alveolar venti- Toxicity of Anesthetic Agents
lation. In addition, all volatile anesthetics are respiratory depres- A. Acute Toxicity
sants, as defined by a reduced ventilatory response to increased 1. Nephrotoxicity—Metabolism of enflurane and sevoflu-
levels of carbon dioxide in the blood. The degree of ventilatory rane may generate compounds that are potentially nephrotoxic.
depression varies among the volatile agents, with isoflurane and Although their metabolism can liberate nephrotoxic fluoride
enflurane being the most depressant. By this hypoventilation ions, significant renal injury has been reported only for enflurane
mechanism, all volatile anesthetics increase the resting level of with prolonged exposure. The insolubility and rapid elimination
Paco in spontaneously breathing patients. of sevoflurane may prevent toxicity. This drug may be degraded
2
Volatile anesthetics also raise the apneic threshold (Paco level by carbon dioxide absorbents in anesthesia machines to form a
2
below which apnea occurs through lack of CO -driven respiratory nephrotoxic vinyl ether compound termed “compound A,” which,
2
stimulation) and decrease the ventilatory response to hypoxia. in high concentrations, has caused proximal tubular necrosis in
Clinically, the respiratory depressant effects of anesthetics are rats. Nevertheless, there have been no reports of renal injury in
overcome by assisting (controlling) ventilation mechanically. humans receiving sevoflurane anesthesia. Moreover, exposure to
The ventilatory depression produced by inhaled anesthetics may sevoflurane does not produce any change in standard markers of
be counteracted by surgical stimulation; however, low, subanes- renal function.
thetic concentrations of volatile anesthetic present after surgery in
the early recovery period can continue to depress the compensa- 2. Hematotoxicity—Prolonged exposure to nitrous oxide
tory increase in ventilation normally caused by hypoxia. decreases methionine synthase activity, which theoretically could
Inhaled anesthetics also depress mucociliary function in the cause megaloblastic anemia. Megaloblastic bone marrow changes
airway. During prolonged exposure to inhaled anesthetics, mucus have been observed in patients after 12-hour exposure to 50%
pooling and plugging may result in atelectasis and the develop- nitrous oxide. Chronic exposure of dental personnel to nitrous
ment of postoperative respiratory complications, including hypox- oxide in inadequately ventilated dental operating suites is a poten-
emia and respiratory infections. tial occupational hazard.
All inhaled anesthetics can produce some carbon monoxide
D. Renal Effects (CO) from their interaction with strong bases in dry carbon
Inhaled anesthetics tend to decrease glomerular filtration rate dioxide absorbers. CO binds to hemoglobin with high affinity,
(GFR) and urine flow. Renal blood flow may also be decreased reducing oxygen delivery to tissues. Desflurane produces the most
by some agents, but filtration fraction is increased, implying that CO, and intraoperative formation of CO has been reported. CO
autoregulatory control of efferent arteriole tone helps compensate production can be avoided simply by using fresh carbon dioxide
and limits the reduction in GFR. In general these anesthetic absorbent and by preventing its complete desiccation.