Page 497 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 27 Skeletal Muscle Relaxants 483

after the initial dose. This transient bradycardia can be prevented Interactions with Other Drugs
by thiopental, atropine, and ganglionic-blocking drugs, and
by pretreating with a small dose of a nondepolarizing muscle A. Anesthetics
relaxant (eg, rocuronium). Direct myocardial effects, increased Inhaled (volatile) anesthetics potentiate the neuromuscular block-
muscarinic stimulation, and ganglionic stimulation contribute ade produced by nondepolarizing muscle relaxants in a dose-
to this bradycardic response. dependent fashion. Of the general anesthetics that have been
studied, inhaled anesthetics augment the effects of muscle relax-
ants in the following order: isoflurane (most); sevoflurane, desflu-
Other Adverse Effects of Depolarizing rane, halothane; and nitrous oxide (least) (Figure 27–8). The most
Blockade important factors involved in this interaction are the following:
A. Hyperkalemia (1) nervous system depression at sites proximal to the neuromus-
cular junction (ie, CNS); (2) increased muscle blood flow (ie, due
Patients with burns, nerve damage or neuromuscular disease, to peripheral vasodilation produced by volatile anesthetics), which
closed head injury, and other trauma may develop proliferation of allows a larger fraction of the injected muscle relaxant to reach
extrajunctional acetylcholine receptors. During administration of the neuromuscular junction; and (3) decreased sensitivity of the
succinylcholine, potassium is released from muscles, likely due to postjunctional membrane to depolarization.
fasciculations. If the proliferation of extrajunctional receptors is great A rare interaction of succinylcholine with volatile anesthet-
enough, sufficient potassium may be released to result in cardiac ics results in malignant hyperthermia, a condition caused by
arrest. The exact time course of receptor proliferation is unknown; abnormal release of calcium from stores in skeletal muscle. This
therefore, it is best to avoid the use of succinylcholine in these cases.
condition is treated with dantrolene and is discussed below under
Spasmolytic & Antispasmodic Drugs and in Chapter 16.
B. Increased Intraocular Pressure
Administration of succinylcholine may be associated with the rapid B. Antibiotics
onset of an increase in intraocular pressure (<60 seconds), peaking Numerous reports have described enhancement of neuromus-
at 2–4 minutes, and declining after 5 minutes. The mechanism cular blockade by antibiotics (eg, aminoglycosides). Many of
may involve tonic contraction of myofibrils or transient dilation of the antibiotics have been shown to cause a depression of evoked
ocular choroidal blood vessels. Despite the increase in intraocular release of acetylcholine similar to that caused by administering
pressure, the use of succinylcholine for ophthalmologic operations magnesium. The mechanism of this prejunctional effect appears
is not contraindicated unless the anterior chamber is open (“open to be blockade of specific P-type calcium channels in the motor
globe”) due to trauma. nerve terminal.

C. Increased Intragastric Pressure C. Local Anesthetics and Antiarrhythmic Drugs
In heavily muscled patients, the fasciculations associated with suc- In small doses, local anesthetics can depress posttetanic poten-
cinylcholine may cause an increase in intragastric pressure ranging tiation via a prejunctional neural effect. In large doses, local
from 5 to 40 cm H O, increasing the risk for regurgitation and anesthetics can block neuromuscular transmission. With these
2
aspiration of gastric contents. This complication is more likely to higher doses, local anesthetics block acetylcholine-induced muscle
occur in patients with delayed gastric emptying (eg, those with contractions as a result of blockade of the nicotinic receptor ion
diabetes), traumatic injury (eg, an emergency case), esophageal channels. Experimentally, similar effects can be demonstrated with
dysfunction, and morbid obesity. sodium channel-blocking antiarrhythmic drugs such as quinidine.
However, at the doses used for cardiac arrhythmias, this interac-
D. Muscle Pain tion is of little or no clinical significance. Higher doses of bupiva-
Myalgias are a common postoperative complaint of heavily caine have been associated with cardiac arrhythmias independent
muscled patients and those who receive large doses (>1.5 mg/kg) of the muscle relaxant used.
of succinylcholine. The true incidence of myalgias related to
muscle fasciculations is difficult to establish because of confound- D. Other Neuromuscular Blocking Drugs
ing factors, including the anesthetic technique, type of surgery, The end plate-depolarizing effect of succinylcholine can be antago-
and positioning during the operation. However, the incidence of nized by administering a small dose of a nondepolarizing blocker.
myalgias has been reported to vary from less than 1% to 20%. It To prevent the fasciculations associated with succinylcholine admin-
occurs more frequently in ambulatory than in bedridden patients. istration, a small nonparalyzing dose of a nondepolarizing drug can
The pain is thought to be secondary to the unsynchronized con- be given before succinylcholine (eg, d-tubocurarine, 2 mg IV, or
tractions of adjacent muscle fibers just before the onset of paraly- pancuronium, 0.5 mg IV). Although this dose usually reduces fas-
sis. However, there is controversy over whether the incidence of ciculations and postoperative myalgias, it can increase the amount
muscle pain following succinylcholine is actually higher than with of succinylcholine required for relaxation by 50–90% and can
nondepolarizing muscle relaxants when other potentially con- produce a feeling of weakness in awake patients. Therefore, “pre-
founding factors are taken into consideration. curarization” before succinylcholine is no longer widely practiced.