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AI-Generated response:

What other agents that depress the central nervous system can exacerbate opioid-induced respiratory distress?

Answer generated on June 5, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

Concomitant use of opioids with benzodiazepines, alcohol, barbiturates, sedatives, hypnotics, and other CNS depressants can exacerbate opioid-induced respiratory distress, leading to profound sedation, respiratory depression, coma, and death.

Extreme caution and close monitoring are necessary when these agents are used together.[1-9]

  • Benzodiazepines and opioids together significantly increase the risk of respiratory depression and sedation, necessitating minimal dosing and strict patient monitoring.[6-9]

  • Alcohol enhances the CNS depressant effects of opioids, potentially leading to severe respiratory depression and even fatal overdose.[1]

  • Barbiturates, when used with opioids, can cause enhanced CNS depression, increasing the risk of respiratory complications.[2-4]

  • Sedatives and hypnotics, including those used for ICU sedation, when co-administered with opioids, may result in profound sedation and respiratory depression.[4-5]

  • Diphenhydramine, a sedating antihistamine, can also potentiate the CNS depressant effects of opioids, leading to increased risk of respiratory depression.[4]

Additional info

When prescribing opioids in conjunction with other CNS depressants, it is crucial to consider the additive effects of these medications on the central nervous system. The FDA and clinical guidelines strongly advise against the concurrent use of these substances unless no alternatives are available and the benefits outweigh the risks. In such cases, the lowest possible doses should be used, and the duration of co-administration should be kept as short as possible. Additionally, prescribing naloxone for emergency treatment of opioid overdose should be considered, and patients should be monitored closely for signs of excessive sedation and respiratory depression. This approach is essential to mitigate the risks associated with the potentiation of CNS depressant effects, which can be life-threatening.

References

Reference 1

1.

Elsevier ClinicalKey Drug Class Overview

Content last updated: November 5, 2017.

Concomitant use of opioids with other central nervous system depressants, including alcohol and benzodiazepines, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant use of these drugs for patients in whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations possible and monitor patients closely for signs and symptoms of respiratory depression and sedation. Concomitant use of alcohol and some extended-release opioid formulations may result in increased opioid plasma concentrations and potentially fatal overdose[40951]. [46350][56303][61143]

Reference 2

2.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Interactions Diphedryl: (Major) Because Diphedryl can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. (Major) Reserve concomitant use of opioids and Diphedryl for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.

Reference 3

3.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Interactions Diphedryl: (Major) Because Diphedryl can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. (Major) Reserve concomitant use of opioids and Diphedryl for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.

Reference 4

4.

Elsevier ClinicalKey Drug Monograph

Content last updated: April 1, 2024.

Interactions Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Because diphenhydramine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus.

Reference 5

5.

Elsevier ClinicalKey Drug Class Overview

Content last updated: June 0, 2020.

Coadministration of sedatives with other central nervous system depressants (e.g., anesthetics, hypnotics, opioids) may cause profound sedation, hypotension, and/or respiratory depression.[[29112]](_WPS/RefShow.aspx?rid=29112) [[31036]](_WPS/RefShow.aspx?rid=31036) [[41537]](_WPS/RefShow.aspx?rid=41537) [[57161]](_WPS/RefShow.aspx?rid=57161)

Reference 6

6.

Elsevier ClinicalKey Drug Class Overview

Content last updated: July 4, 2020.

A boxed warning in the labels for all benzodiazepines warns about the risks of coadministration of benzodiazepines and opioids. Concomitant use of benzodiazepines and opioids increases the risk of respiratory depression, low blood pressure, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and prescription durations to the minimum required, and monitor patients for signs and symptoms of respiratory depression and sedation[61143]. Concomitant administration of benzodiazepines with other CNS depressant drugs, including alcohol, also generally produces additive CNS depressant effects. Patients should be advised to avoid ingestion of alcoholic beverages during treatment with a benzodiazepine. In addition to alcohol, medications such as psychotropic medications, anticonvulsants, sedating antihistamines, and many other medications that produce CNS sedation may have additive effects with the benzodiazepines[62827].

Reference 7

7.

Food and Drug Administration (DailyMed).

Publish date: April 5, 2024.

Warnings And Cautions Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.6) ] . 5.4 Risks from Concomitant Use With Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Hydromorphone Hydrochloride Injection [high potency formulation (HPF)] with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7) ]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.

Reference 8

8.

Food and Drug Administration (DailyMed).

Publish date: December 3, 2023.

Drug Interactions Table <table border="1" cellpadding="0" width="100%"><tbody><tr><td colspan="2"><paragraph><content styleCode="bold">Benzodiazepines and Other Central Nervous System (CNS) Depressants</content></paragraph></td></tr><tr><td><paragraph><content styleCode="italics">Clinical Impact</content></paragraph></td><td><paragraph>Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. The depressant effects of morphine are potentiated by the presence of other CNS depressants. Use of neuroleptics in conjunction with neuraxial morphine may increase the risk of respiratory depression.</paragraph></td></tr><tr><td><paragraph><content styleCode="italics">Intervention</content></paragraph></td><td><paragraph>Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see <content styleCode="italics">Warnings and Precautions</content> ( <linkHtml href="https://direct.fda.gov/apex/f?p=100:114:100632129771702:EDIT::114:P114_CNTNT_ID:3844020&amp;cs=34D125F53D4416D862E7C888ED477517D#id_link_72c6c635-f817-1b8e-e053-2a91aa0a3b33">5.5</linkHtml>)].

Reference 9

9.

Food and Drug Administration (DailyMed).

Publish date: January 2, 2023.

Drug Interactions 7 DRUG INTERACTIONS The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation. Benzodiazepines, including DORAL (quazepam), produce additive CNS depressant effects when co-administered with ethanol or other CNS depressants (e.g. psychotropic medications, anticonvulsants, antihistamines). Downward dose adjustment of DORAL (quazepam) and/or concomitant CNS depressants may be necessary because of additive effects. CNS Depressants: downward dose adjustment may be necessary due to additive effects ( 7 )

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