Class Explorer · Pain & inflammation

Opioids

Mu receptor agonists in the dorsal horn, brainstem and limbic system: less pain signal ascending, less distress about the pain that arrives, and less respiratory drive.

Members

MorphineThe reference opioid, and the one the kidney cannot forgive.HydromorphoneMorphine's substitute when the kidneys fail, and five times as strong by mouth.OxycodoneReliable oral absorption, and a combination product that hides a second drug.CodeineA prodrug whose effect depends on an enzyme nobody has measured.TramadolPart opioid, part antidepressant, and it lowers the seizure threshold.

Also in this class: Fentanyl · Methadone · Buprenorphine. Full pages arrive as the library grows.

Compare the members

Drug	In renal impairment	Prodrug?	Note
Morphine	Accumulates, avoid	No	The reference opioid for equianalgesia
Hydromorphone	Preferred	No	Roughly five times morphine's potency orally
Oxycodone	Caution	No	Higher oral bioavailability than morphine
Codeine	Avoid	Yes, CYP2D6	Unpredictable; falling out of favour
Tramadol	Caution	Partly, CYP2D6	Serotonergic and seizure risk

Morphine

In renal impairment: Accumulates, avoid
Prodrug?: No
Note: The reference opioid for equianalgesia

Hydromorphone

In renal impairment: Preferred
Prodrug?: No
Note: Roughly five times morphine's potency orally

Oxycodone

In renal impairment: Caution
Prodrug?: No
Note: Higher oral bioavailability than morphine

Codeine

In renal impairment: Avoid
Prodrug?: Yes, CYP2D6
Note: Unpredictable; falling out of favour

Tramadol

In renal impairment: Caution
Prodrug?: Partly, CYP2D6
Note: Serotonergic and seizure risk

Shared across the class

Indications: Moderate to severe acute pain · Cancer pain · Breathlessness in palliative care
Adverse effects: Constipation, which never abates · Nausea, which does · Sedation · Respiratory depression · Tolerance, dependence, and use disorder
Contraindications: Respiratory depression · Concurrent sedative use without a plan
Monitoring: Pain score and function, not pain score alone · Sedation score, which precedes respiratory depression · Bowel function from day one · Total daily dose and duration

What makes each agent different

Morphine has renally-cleared active metabolites; in kidney failure they accumulate and produce sedation and myoclonus. Hydromorphone is the usual substitute for exactly that reason.
Codeine and tramadol are prodrugs needing CYP2D6: ultra-rapid metabolisers get an unexpected overdose, poor metabolisers get no analgesia at all. Both problems are common and neither is visible in advance.
Tramadol also inhibits serotonin and noradrenaline reuptake, so it carries serotonin-syndrome and seizure risk that the rest of the class does not.

Every opioid prescription is also a laxative prescription. The constipation is a receptor effect in the gut and does not resolve with time.

Sedation is the early warning; by the time the respiratory rate falls, the margin is already gone.

Codeine is contraindicated in children after tonsillectomy and in breastfeeding, both because of the ultra-rapid metaboliser problem.

Last reviewed 2026-08-16 · Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed.