Nursing care
Opioid Antagonists: what to check before you give it
Written and reviewed by Dana Whitfield, RN, MSN · 6 min read · Updated September 2026
Short answer
Opioid antagonists such as naloxone and naltrexone block opioid receptors to reverse or prevent opioid effects. Naloxone has a shorter half-life than most opioids it is used to reverse, so a patient can re-sedate once it wears off, which means continued monitoring after reversal is essential, not optional. Naltrexone is used for maintenance, not emergency reversal.
What it does and why it is prescribed
Opioid antagonists bind to opioid receptors, mainly the mu receptor, without activating them, which displaces the opioid already bound and blocks further opioid effect. Naloxone is the emergency reversal agent given for suspected opioid overdose, respiratory depression, or oversedation after opioid administration in a clinical setting. Naltrexone works the same way pharmacologically but is used differently, as a maintenance therapy to prevent relapse in opioid or alcohol use disorder, because sustained receptor blockade removes the reward from using again.
You will encounter naloxone most often as an emergency intervention, whether in a community overdose response, in post-operative recovery after an opioid-related respiratory event, or as a take-home kit dispensed to patients on high-dose opioid therapy. Naltrexone appears in a different context entirely, typically outpatient, and it is critical that patients on naltrexone maintenance are opioid-free for a defined period before starting it, or they will go into acute precipitated withdrawal.
Nursing considerations before giving it
Before giving naloxone, confirm the clinical picture actually fits opioid toxicity: pinpoint pupils, respiratory rate below the threshold set by protocol or unit policy, and reduced level of consciousness in a patient known or suspected to have taken opioids. Have resuscitation equipment and oxygen available, since reversal can be incomplete or the patient may need airway support regardless of the antagonist given.
Before starting naltrexone, confirm the patient has been opioid-free for the period specified by the prescriber, generally seven to ten days depending on the opioid used, and consider a naloxone challenge test if there is any doubt. Starting naltrexone in a patient who still has opioid on board precipitates a sudden, severe withdrawal reaction rather than the gradual antagonism intended, and this is a distinct risk from anything seen with naloxone.
What to monitor
After giving naloxone, monitor respiratory rate, level of consciousness, and oxygen saturation continuously, not just at the point of reversal. This is where the pharmacology matters directly: naloxone has a shorter half-life than most opioids it is reversing, so its effect can wear off while the opioid is still active in the patient's system, allowing sedation and respiratory depression to return. The patient needs monitoring for a period well beyond the point they appear to wake up, with the exact duration depending on which opioid was involved and its own half-life.
Also monitor for signs of acute opioid withdrawal after naloxone, including agitation, tachycardia, sweating, and pain out of proportion to what was previously controlled, particularly in patients who were opioid-dependent before the overdose or oversedation event. For naltrexone, monitor liver function periodically, since the drug carries a hepatotoxicity risk, and monitor mood, as it has been associated with depressive symptoms in some patients during maintenance therapy.
Side effects versus adverse effects
Expected side effects of naloxone include the withdrawal-like symptoms already described: agitation, nausea, sweating, and return of pain, which are an anticipated consequence of receptor blockade in an opioid-tolerant patient rather than a complication in themselves. For naltrexone, nausea, headache, and injection-site reactions with the extended-release form are common and usually tolerable.
The adverse effect that changes management is re-sedation after apparent reversal with naloxone, because it signals the antagonist has worn off while opioid remains active, and the patient needs another dose or an infusion, plus airway support if respiratory depression returns. For naltrexone, the adverse effect to escalate is signs of hepatotoxicity, such as right upper quadrant pain, jaundice, or dark urine, and any indication the patient has used opioids anyway, which risks a severe precipitated withdrawal reaction.
What to hold for and when to call
Do not withhold naloxone in a genuine emergency; the priority is reversing respiratory depression, and dosing follows protocol or medical direction rather than routine hold criteria. After the initial dose, call immediately if the patient's respiratory rate or level of consciousness declines again, since this indicates the naloxone has worn off before the opioid has cleared and a repeat dose or infusion is needed.
Hold naltrexone and call the prescriber if the patient reports any opioid use, however small, in the days before the scheduled dose, or if liver function tests come back abnormal. Also hold and escalate if a patient on naltrexone maintenance presents in significant pain requiring opioid analgesia, since standard opioid doses will be blocked and the situation needs specialist input rather than simply increasing the opioid dose.
Patient teaching
Teach patients and families receiving a take-home naloxone kit that reversal can be temporary and that emergency services should still be called even if the person wakes up, because re-sedation is a real risk once the naloxone wears off and the opioid is still active. Show them how to give a second dose if there is no response within the time specified on the kit, and explain that naloxone will not cause harm if given to someone who turns out not to be experiencing an opioid overdose.
For patients starting naltrexone, explain clearly that using opioids while on the drug will not produce the expected effect and will not overcome the blockade by taking more, a misunderstanding that has led to fatal overdose attempts. Reinforce that they must tell any treating clinician they are on naltrexone before receiving opioid analgesia for surgery or trauma, since standard doses will be ineffective and alternative pain management needs planning in advance.
The next step on this is the same as on everything else here: answer questions and read the rationales. Our pharmacology practice questions are the closest set to what this page covers.
One question from the pharmacology set
A client with heart failure is started on furosemide 40 mg PO daily. Which findings should the nurse report to the provider before administering the next dose? Select all that apply.
Rationale
Furosemide is a loop diuretic, so the two things you are watching are potassium and kidney function. A potassium of 2.9 mEq/L is below the 3.5–5.0 reference range and puts the client at risk for dysrhythmia — hold and report. Muscle cramps with palpitations are the clinical face of that same hypokalemia, so they are reported together, not separately. A creatinine that doubles signals the diuresis has outrun renal perfusion. A blood pressure of 132/78 and a 1 kg loss are the expected response to the drug working, not reasons to hold it.
Answer: A, D, E
Common questions
Why does a patient need monitoring after naloxone reverses an overdose?
Naloxone has a shorter half-life than most opioids it is used to reverse, so its effect can wear off while the opioid is still active in the body. This means the patient can slip back into sedation and respiratory depression after appearing to recover, so continued monitoring of respiratory rate and consciousness is essential, not optional.
What is the difference between naloxone and naltrexone?
Both block opioid receptors, but they are used differently. Naloxone is a fast-acting emergency reversal agent for opioid overdose or oversedation, while naltrexone is a longer-acting maintenance therapy used to prevent relapse in opioid or alcohol use disorder, started only after the patient has been opioid-free for a set period.
What happens if you start naltrexone too soon after opioid use?
The patient can go into acute precipitated withdrawal, which is sudden and severe rather than the gradual reaction seen when opioids are simply stopped. This is why confirming an opioid-free period, and sometimes a naloxone challenge test, is done before the first dose.
Can a patient on naltrexone still get pain relief from opioids?
Standard opioid doses will be blocked by naltrexone and will not provide effective analgesia. Patients need to disclose naltrexone use before any procedure likely to require opioid pain control, so the team can plan alternative pain management in advance rather than escalating opioid doses against the blockade.
What withdrawal symptoms should you expect after giving naloxone?
Agitation, tachycardia, sweating, nausea, and return of pain are expected in an opioid-dependent patient once naloxone displaces the opioid from its receptors. These symptoms confirm the antagonist is working and are managed supportively, distinct from re-sedation, which signals the naloxone itself has worn off.
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