Mechanism of Action

Bind mu-opioid receptors in the brain, spinal cord, and peripheral tissues, mimicking endogenous endorphins. The same binding event produces analgesia, euphoria, sedation, and respiratory depression. Full agonists (morphine, hydromorphone, fentanyl, oxycodone) have no analgesic ceiling — increasing the dose increases effect and overdose risk. Mixed agonist-antagonists (butorphanol, nalbuphine) hit kappa while limiting mu, giving a ceiling effect but precipitating withdrawal in a client already on a full agonist. Partial agonists (buprenorphine) bind mu with high affinity but submaximal activation. Morphine is the gold standard for acute severe pain and the equianalgesic reference; fentanyl is 50–100× more potent (smaller dose, same maximum relief); hydromorphone is preferred in renal impairment.

Common Medications

morphinePrototype

gold standard for acute severe pain; equianalgesic reference; avoid in renal failure (neurotoxic metabolites)

hydromorphone

preferred in renal impairment; ~5× more potent than morphine

fentanyl

50–100× morphine potency; rapid-onset IV/transdermal

oxycodone

oral full agonist

methadone

long-acting; OUD maintenance

buprenorphine

partial agonist; OUD and chronic pain

butorphanol

mixed agonist-antagonist

nalbuphine

mixed agonist-antagonist

Indications

moderate-to-severe acute pain

full agonists; e.g. post-operative pain

chronic cancer pain

moderate pain

mixed agonist-antagonists with a ceiling effect

opioid use disorder maintenance

methadone, buprenorphine

Side Effects

constipation Hallmark

the ONE effect tolerance never develops to — start a prophylactic bowel regimen (stool softener + stimulant laxative) with the first dose

sedation

earliest warning sign — precedes respiratory depression; sedation before desaturation

nausea

worst first 24–72 h; often resolves

vomiting

urinary retention

orthostatic hypotension

vasodilation + blunted baroreceptor reflex

pruritus

histamine-mediated, NOT a true allergy — don't reflexively chart an allergy for itching alone

miosis

pinpoint pupils

Contraindications & Interactions

Contraindications

respiratory depression / acute asthma

uncontrolled — opioids further depress drive

paralytic ileus

Interactions

benzodiazepines

additive CNS/respiratory depression — FDA boxed warning for the combination

alcohol

additive CNS depression

other CNS depressants

sedatives, hypnotics, muscle relaxants

mixed agonist-antagonists

precipitate withdrawal in a full-agonist-dependent client — never combine

Administration & Monitoring

assess sedation level before counting respirations

use a sedation scale (e.g. POSS); rising drowsiness is the earliest warning

hold dose for respiratory depressionHoldRR < 12/min

or if difficult to arouse; stimulate, notify provider

keep naloxone accessible

assess pain with a validated scale

before and after each dose

dose around-the-clock for continuous pain

scheduled dosing prevents pain cycling; start low and titrate

start a prophylactic bowel regimen

with the first opioid dose

fall precautions

raise side rails; CNS depression + orthostasis

reduce equianalgesic dose by 25–50% when rotating opioids

incomplete cross-tolerance; verify all conversions

taper to discontinue

20–25% every 1–2 days to prevent withdrawal in a physically dependent client

Patient Teaching

report difficulty breathing immediately

report excessive drowsiness

avoid alcohol

avoid other CNS depressants

including benzodiazepines

do not drive until effects are known

change positions slowly

orthostatic hypotension

use the bowel regimen as prescribed

constipation does not improve with time

do not stop abruptly

physical dependence — taper to avoid withdrawal

Report Nowescalate immediately

respiratory depressionBlack BoxRR < 12/min

FDA boxed warning; most dangerous effect — progression is pain relief → sedation → respiratory depression; hold the dose, stimulate, notify provider; reversal = naloxone titrated to restore respirations (not full consciousness), and its 30–90 min duration is shorter than morphine's 2–4 h so monitor for re-narcotization

opioid overdose triad Hallmark

respiratory depression + decreased LOC + pinpoint pupils; support airway with BVM, give naloxone

addiction / misuse

FDA boxed warning for abuse, addiction, and misuse; behavioral pattern — distinct from physical dependence

precipitated withdrawal

giving a mixed agonist-antagonist to a client already on a full agonist triggers acute withdrawal

Clinical Pearl

Sedation before desaturation — assess level of consciousness before you count respirations; the sleepy patient is your red flag, not the number on the pulse ox. And constipation is the one side effect the body never tolerates, so start the bowel regimen with the first dose.