NUR 5213 Module 5 Comparative Drug Class Analysis Example

The Second Dose That Could Not Work: Serotonin Antagonists and Dopamine Antagonists for Postoperative Nausea Compared, So Nurses Choose a Rescue by Receptor

Student Name

American College of Education

NUR5213: Advanced Pharmacology for Health Educators

Module 5 Assignment

Instructor Name

April 4, 2028

The Practice Problem

On the surgical units of the composite community hospital where the author works in professional development, most patients having general anesthesia receive ondansetron in the operating room to prevent nausea. Postoperative order sets then list ondansetron every six hours as needed, with prochlorperazine or metoclopramide as a second option. A review of 60 patients with nausea on the evening of surgery found that 34 received ondansetron as their first rescue dose within four hours of the operating room dose, and that in 21 of those the nausea continued until a second drug was given. Nurses described ondansetron as the stronger drug and the other options as a last resort. The comparison below explains why that reasoning is backward for a patient who has already had ondansetron.

How Postoperative Nausea Is Produced

Nausea and vomiting are coordinated by a network in the brainstem that receives signals from several sources. The chemoreceptor trigger zone in the area postrema, which lies outside the blood-brain barrier, detects drugs and toxins in the blood, including opioids and some anesthetic agents. The gut sends signals through the vagus nerve when it is stretched, handled or irritated, as it is during abdominal surgery. The vestibular system contributes when a patient moves after anesthesia. Different neurotransmitters carry these signals: serotonin acting at 5-HT3 receptors is especially important in the vagal pathway from the gut and in the trigger zone, while dopamine acting at D2 receptors is especially important in the trigger zone. That is why drugs that block different receptors can each reduce nausea, and why combining or switching classes can help when one is not enough.

The Two Classes Compared

Mechanism. Serotonin 5-HT3 antagonists, of which ondansetron is the most used, block serotonin at 5-HT3 receptors on vagal nerve endings in the gut and in the trigger zone. Dopamine D2 antagonists used for nausea include phenothiazines such as prochlorperazine, butyrophenones such as droperidol and haloperidol, and metoclopramide, which also increases gastric emptying. They block dopamine in the trigger zone.

Efficacy. For prevention, different antiemetics are more alike than different. In a large factorial trial of six interventions, ondansetron, dexamethasone and droperidol each reduced the risk of postoperative nausea and vomiting by about 26%, each acted independently of the others, and their effects combined multiplicatively, leading the authors to recommend that the safest or least expensive be used first (Apfel et al., 2004). Neither class is simply stronger.

Rescue. When nausea occurs despite prophylaxis, current consensus guidelines recommend a rescue antiemetic from a different class from the one given for prevention, because repeating a drug whose receptors are already blocked adds little (Gan et al., 2020). A patient who is nauseated four hours after ondansetron is nauseated with 5-HT3 receptors already occupied; another dose knocks on a door that is already closed.

Adverse effects. Ondansetron commonly causes headache and constipation. Both classes can prolong the QT interval on the electrocardiogram, a concern in patients with known QT prolongation, low potassium or magnesium, or other QT-prolonging drugs. The dopamine antagonists carry a distinct set of risks because dopamine blockade also affects movement pathways: acute dystonia, particularly in young adults, and akathisia, an intense inner restlessness that patients may describe as anxiety and nurses may mistake for agitation. Metoclopramide carries a warning about tardive dyskinesia with prolonged use. Sedation is more common with phenothiazines and butyrophenones than with ondansetron.

Cautions. Dopamine antagonists should generally be avoided in patients with Parkinson's disease, because blocking dopamine worsens their symptoms, and ondansetron is usually the better choice for them. For most other adults who have had ondansetron in the operating room, a dopamine antagonist is a reasonable first rescue, with attention to QT risk and watch for restlessness.

Safety Checks Before the Rescue Dose

Choosing a different class solves the efficacy problem but creates a new safety question, because the dopamine antagonists carry risks that ondansetron does not, and nurses need a short set of checks before giving them. The first is movement. Akathisia after a dopamine antagonist is common, not rare. In a study of emergency department patients given a single intravenous dose of prochlorperazine, 44% developed akathisia within an hour, graded as moderate or severe in 30 of the 100 patients, while none of the patients given saline or antibiotics did (Drotts & Vinson, 1999). Postoperative patients who suddenly become restless, cannot lie still or try to climb out of bed after a rescue antiemetic may be experiencing a drug effect rather than pain or delirium. Nurses should ask about the feeling of inner restlessness, give the dose slowly and report it promptly, because it responds to treatment and because a patient who has had it once should not receive the same drug again.

The second check is the heart rhythm. Both classes can prolong the QT interval, and the risk accumulates with other drugs and conditions. In hospitalized patients in cardiac care units, a validated risk score identified female sex, low potassium, loop diuretic use, heart failure, sepsis and the number of QT-prolonging drugs among the independent predictors of significant QT prolongation (Tisdale et al., 2013). Surgical patients may carry several of these at once, especially older women receiving diuretics. Before a rescue dose, nurses should look at the most recent potassium and magnesium, any recent electrocardiogram and the medication list for other QT-prolonging drugs, and should ask for guidance when several risks are present. The third check is Parkinson's disease or other movement disorders, in which a dopamine antagonist should not be used without prescriber review. These three checks take less than a minute and belong on the same line of the order set as the rescue option itself.

Teaching the Rule

The rule for nurses is short: check what was given in the operating room, and rescue with a different class. The author's teaching session builds it in three steps. First, nurses review the receptors on a simple diagram of the vomiting pathway and place each drug on its receptor. Second, they work through four brief cases: a patient given ondansetron in the operating room who is nauseated in the recovery unit; a patient with Parkinson's disease; a patient on methadone with a long QT interval; and a 22-year-old who becomes restless and cannot sit still an hour after prochlorperazine. For each, nurses choose a rescue drug or a concern and explain it by receptor. Third, the order set will be revised so that the first as-needed option listed depends on what was given for prophylaxis, and the anesthesia record's prophylaxis entry will display on the postoperative medication screen, a system change that makes the rule easier to follow than to ignore.

The effect will be measured by repeating the 60-patient review three months after the session: the proportion of first rescue doses given from a different class than prophylaxis, and the proportion of patients whose nausea resolved after the first rescue dose. Nurses will also complete a four-case quiz immediately and at 60 days to check whether the reasoning, not just the rule, has been retained.

References

Apfel, C. C., Korttila, K., Abdalla, M., Kerger, H., Turan, A., Vedder, I., Zernak, C., Danner, K., Jokela, R., Pocock, S. J., Trenkler, S., Kredel, M., Biedler, A., Sessler, D. I., & Roewer, N. (2004). A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. New England Journal of Medicine, 350(24), 2441-2451. https://doi.org/10.1056/NEJMoa032196

Drotts, D. L., & Vinson, D. R. (1999). Prochlorperazine induces akathisia in emergency patients. Annals of Emergency Medicine, 34(4), 469-475. https://doi.org/10.1016/S0196-0644(99)80048-1

Gan, T. J., Belani, K. G., Bergese, S., Chung, F., Diemunsch, P., Habib, A. S., Jin, Z., Kovac, A. L., Meyer, T. A., Urman, R. D., Apfel, C. C., Ayad, S., Beagley, L., Candiotti, K., Englesakis, M., Hedrick, T. L., Kranke, P., Lee, S., Lipman, D., ... Philip, B. K. (2020). Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesthesia & Analgesia, 131(2), 411-448. https://doi.org/10.1213/ANE.0000000000004833

Tisdale, J. E., Jaynes, H. A., Kingery, J. R., Mourad, N. A., Trujillo, T. N., Overholser, B. R., & Kovacs, R. J. (2013). Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circulation: Cardiovascular Quality and Outcomes, 6(4), 479-487. https://doi.org/10.1161/CIRCOUTCOMES.113.000152