Monitor Patients for Opioid-Induced Adverse Drug Events

Because opioids have no analgesic ceiling, they are the most powerful tool for managing acute and chronic pain. Over the past few decades, the number of prescriptions for opioids has increased substantially worldwide. In 2017, more than 191 million opioid prescriptions were dispensed to Americans.¹ That same year, more than 47,000 deaths occurred as a result of opioid overdose.² More than 50% of hospitalized patients receive opioids at some point during their stay. In addition, more than 95% of surgical patients receive opioids.³

Opioids are known to have opioid-related adverse drug events (ORADEs), which affect most organ systems and range from mild constipation to circulatory arrest.³ The more common ORADEs include nausea, physical dependence, respiratory depression, sedation, tolerance, constipation, and vomiting.

Opioids attach to opioid receptors on nerve cells and act to decrease pain perception. Opioid receptors are found extensively in the brain and spinal cord, as well as the circulatory, gut, and lung systems. Most common ORADEs occur in these systems.

NAUSEA AND VOMITING

Opioid-induced nausea and vomiting (OINV) occurs in approximately one-third of patients who receive opioids. It is a significant factor in several complications, including dehydration, electrolyte imbalances, and pulmonary aspiration.⁴

The exact mechanism of OINV is unclear. However, some studies have shown a correlation between nausea and vomiting with an intravestibular mismatch, similar to motion sickness. Therefore, prevention of OINV can be achieved if the patient stays still after opioid dosing. Moving the head less has been shown to decrease a patient’s OINV.⁴

There are 4 options for treating OINV: dose reduction, opioid switch, route of administration change, and medications such as antiemetics, corticosteroids, and metoclopramide.⁵

CONSTIPATION

Opioid drugs inhibit gastric emptying and peristalsis in the gastrointestinal tract. This results in delayed absorption of medica- tions and increased absorption of fluids, leading to constipation and hard stools. Approximately 50% of patients taking opioids develop opioid-induced constipa- tion (OIC), which may occur immediately following the start of therapy or develop over time. This is not an adverse event (AE) that decreases over time.

To prevent OIC, patients should increase their dietary fiber, exercise, and fluid intake and begin laxative therapy and/or a stool softener at the same time opioid therapy begins. All types of laxatives can be used, except for bulk-forming laxatives such as psyllium. Bulk-forming laxatives can increase the bulk of the stool and distend the colon, contributing to the obstruction and worsening abdominal pain.⁶

Once OIC has developed, treatment relief is often incomplete and slow. Stimulant laxatives, such as senna or bisacodyl with or without a stool softener, commonly are used to treat OIC. Daily doses of an osmotic laxative, such as polyethylene glycol, also can be used. Saline laxatives, such as magnesium citrate, are another option.⁶

For refractory OIC, subcutaneous methylnaltrexone is the most effective. Other therapies include alvimopan (Entereg), liposomes, naldemedine, and naloxegol.⁶

SEDATION

Sedation is a dose-dependent effect of opioids and occurs in approximately 40% of patients. Most patients will develop a tolerance to the sedative properties of opioids, but some may need a dose reduction.⁷

The best way to prevent sedation and other dose-related AEs is to use the lowest effective opioid dose. If sedation persists, switching to another opioid may help. In addition, minimizing unnecessary medications or using antipsychotics and stimulants judiciously may help manage central nervous system AEs.⁷

PHYSICAL DEPENDENCE AND TOLERANCE

Physical dependence on opioids develops after repeated use over a long period of time. When the drug is discontinued, the body goes through withdrawal, which can be life-threatening. To prevent withdrawal, patients should taper doses of opioids gradually.⁸

Tolerance to an opioid develops when a patient no longer responds to the drug dose that worked at the beginning of therapy. It takes a dose increase to achieve the same pain relief they originally achieved.⁸

RESPIRATORY DEPRESSION

Respiratory depression is a major ORADE that often leads to death. The drug development community is investigating opioids that do not affect the respiratory system, as well as respiratory stimulants such as ampakines, 5-HT agonists, and phosphodiesterase-4 inhibitors.⁹

Naloxone is the mainstay for treatment of opioid-induced respiratory depression (OIRD). Naloxone displaces opioids from the μ-receptors and reverses opioid overdose within minutes. It rapidly reestablishes independent breathing and return of consciousness. Unfortunately, naloxone has a short half-life, especially compared with the duration of action of many opioids. Thus, the effects of naloxone may wane before the respiratory depression effects of the opioid end, which may lead to a recurrence of OIRD. Repeat doses may be necessary.⁹

CONCLUSION

With the increase in opioid overdoses, prescriptions, and use, it is important to know the common AEs and how to prevent and treat them.

Keeping patients comfortable and safe is an integral part of what pharmacists do. It is imperative to monitor patients taking opioids to reduce diversion and manage some of the adverse events these opioids can create.

Kathleen Kenny, PharmD, RPh, has more than 25 years of experience as a community pharmacist and is a freelance clinical medical writer based in Colorado Springs, Colorado.

REFERENCES

1. Prescriptionopioids.CDC.August29,2017.Accessed October 13, 2021.https://www.cdc.gov/opioids/basics/ prescribed.html
2. Opioid overdose crisis. National Institute on Drug Abuse. March 11, 2021. Accessed October 13, 2021. https://www. drugabuse.gov/drug-topics/opioids/opioid-overdose-crisis
3. Stone AB, Jones MR, Rao N, Urman RD. A dashboard for monitoring opioid-related adverse drug events following surgery using a national administrative database. Am J Med Qual. 201934(1):45-52. doi:10.1177/1062860618782646
4. Heuser F, Schultz C, Saglam M, et al. Preventing opioid-in- duced nausea and vomiting: rest your head and close your eyes? PLoS One. 2017;12(3):e0173925. doi:10.1371/journal. pone.0173925
5. Sande TA, Laird BJA, Fallon MT. The management of opioid-induced nausea and vomiting in patients with cancer: a systematic review. J Palliat Med. 2019;22(1):90-97. doi:10.1089/jpm.2018.0260
6. Sizar O, Genova R, Gupta M. Opioid induced constipation. In: StatPearls [Internet]. StatPearls Publishing; 2021.
7. Bourdeanu L, Loseth DB, Funk M. Management of opi- oid-induced sedation in patients with cancer. Clin J Oncol Nurs. 2005;9(6):705-711. doi:10.1188/05.CJON.705-711
8. Tolerance,dependence,addiction:what’sthedifference? National Institute on Drug Abuse. January 12, 2017. Accessed October 13, 2021. https://archives.drugabuse.gov/blog/post/ tolerance-dependence-addiction-whats-difference
9. Dahan A, van der Schrier R, Smith T, Aarts L, van Velzen M, Niesters M. Averting opioid-induced respiratory depression without affecting analgesia. Anesthesiology. 2018;128(5):1027-1037. doi:10.1097/ ALN.0000000000002184