Pharmacology · Opioids and antagonists
Hydrocodone !
A semi-synthetic μ agonist for severe pain and, in some countries, cough; often combined with paracetamol. Part of it is activated to hydromorphone.
Updated 2026-11-01
The figure shows morphine in the μ receptor; hydrocodone, a codeine derivative, occupies the same site. There is no structure of hydrocodone in the receptor.
Mechanism of action
Hydrocodone is a semi-synthetic μ agonist related to codeine. It activates the μ receptor and reduces pain transmission; it also suppresses the cough reflex. In the liver CYP2D6 converts it to hydromorphone, which is more potent, and CYP3A4 to norhydrocodone.
- Activates the μ receptor in the pain pathway
- CYP2D6 makes hydromorphone, a more potent agonist
- Less pain transmission and a weaker cough reflex
- CYP3A4 inactivates it: its inhibitors raise levels
Pharmacokinetics
- Absorption
- By mouth; immediate-release (often with paracetamol) and extended-release forms exist.
- Metabolism
- Liver: CYP3A4 to norhydrocodone and CYP2D6 to hydromorphone.
Indications
- Severe, persistent pain needing an opioid when other options are not enough (extended-release form)
- Acute pain, in combination with paracetamol
- Cough (in antitussive combinations)
Adverse effects
Common
- Nausea, vomiting and abdominal pain
- Sweating
- Lower sexual desire or erectile dysfunction
Contraindications
- Significant respiratory depression
- Acute or severe bronchial asthma without monitoring or resuscitation equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to the drug
Key interactions
- CYP3A4 inhibitors (macrolides, azoles, ritonavir), or stopping inducers (rifampicin, carbamazepine, phenytoin)
- Raise opioid levels and can cause a fatal overdose.
- Benzodiazepines, alcohol and other central nervous system depressants
- Add up to profound sedation, respiratory depression, coma and death.
What is monitored
- Respiratory rate and sedation
- Bowel habits
- Total paracetamol if it is a combination product
Administration and safety
- Extended-release capsules are swallowed whole; crushing, chewing or dissolving the beads releases a potentially fatal dose.
- With combination products, paracetamol from all sources is added up.
- Controlled medicine: the order is verified, every dose recorded and leftovers kept secure.
Nursing care
- Before each dose: respiratory rate, oxygen saturation and sedation level; hold the dose and report excessive sedation or slow breathing.
- Keep naloxone at hand and teach the family to recognise an overdose.
- Prevent constipation from the start and track bowel habits.
- Prevent falls: dizziness, drowsiness and orthostatic hypotension.
- Teach the patient to lock the medicine away and dispose of leftovers safely.
Pregnancy and breastfeeding
Prolonged use in pregnancy can cause neonatal opioid withdrawal syndrome, which is expected and treatable; the newborn is watched after birth.
Test yourself
Think of the answer, then tap the question to see it.
Which more potent metabolite does hydrocodone form, and through which enzyme?
Hydromorphone, through CYP2D6.
What extra risk does combining hydrocodone with paracetamol carry?
Paracetamol hepatotoxicity if several sources of it are added up.
What happens if extended-release hydrocodone capsules are crushed?
The whole dose is released at once and a fatal overdose can follow.
Related drugs
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Hydrocodone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); HYDROCODONE BITARTRATE capsule, extended release (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 23 (McGraw Hill, 2023); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.