Opioids.
Opioids are the class where one receptor explains both why the drug works and why it is dangerous. Mu receptors sit in the spinal cord and brain, and also in the brainstem respiratory centre and throughout the gut wall, which is why analgesia, respiratory depression and constipation are the same pharmacology in three different places.
The mechanism in one sentence
Opioids activate mu receptors, reducing neuronal excitability and neurotransmitter release along pain pathways and everywhere else those receptors appear.
Mu opioid receptors are G-protein coupled and inhibitory. Activation opens potassium channels and closes calcium channels, hyperpolarising the neuron and reducing neurotransmitter release. In the dorsal horn and the periaqueductal grey this dampens pain transmission. In the medulla it reduces the respiratory centre’s sensitivity to rising carbon dioxide, which is the mechanism of fatal overdose. In the enteric nervous system it slows propulsive motility, which is the mechanism of constipation. One receptor, three consequences, and only the first is wanted.
Members of the class
| Drug | What sets it apart |
|---|---|
| Morphine | The reference opioid; renally cleared active metabolite accumulates in renal impairment. |
| Codeine | A prodrug requiring CYP2D6 conversion to morphine. |
| Tramadol | Weak mu agonism plus serotonin and noradrenaline reuptake inhibition, hence serotonin syndrome risk. |
| Oxycodone | Potent oral agonist, less dependent on CYP2D6 than codeine. |
| Fentanyl | Highly lipophilic and far more potent; transdermal and parenteral routes. |
| Buprenorphine | Partial agonist with high receptor affinity, giving a ceiling on respiratory depression. |
What the class is used for
- Moderate to severe acute pain
- Cancer and palliative pain
- Breathlessness in palliative care
- Opioid dependence, using methadone or buprenorphine
Side effects, derived from the mechanism
Each entry below follows from the mechanism above rather than being a separate fact. Read the middle column as the answer to the question, why would that happen.
| Effect | Why it follows |
|---|---|
| Respiratory depression | Mu receptors in the brainstem blunt the ventilatory response to carbon dioxide. This is dose-dependent and is the effect that kills in overdose. |
| Constipation | Mu receptors in the gut wall slow motility. Tolerance develops to sedation and nausea but not to this, which is why a laxative is co-prescribed for the duration rather than temporarily. |
| Nausea and vomiting | Stimulation of the chemoreceptor trigger zone, plus delayed gastric emptying. Usually settles within days as tolerance develops. |
| Sedation and confusion | Central mu activation; more pronounced in older adults and in renal impairment where metabolites accumulate. |
| Miosis | Parasympathetic outflow to the pupil is disinhibited, giving the pinpoint pupils of the opioid toxidrome. |
| Tolerance and dependence | Receptor adaptation to sustained agonism, which is why dose escalation and withdrawal on cessation are expected pharmacology rather than moral failures. |
Contraindications and cautions
- Acute respiratory depression and untreated raised intracranial pressure
- Caution in renal impairment, particularly with morphine
- Caution combining tramadol with serotonergic drugs
The part you cannot derive
Naloxone has a shorter half-life than many opioids, so a patient who wakes after reversal can re-sedate once it wears off while the opioid is still bound. Successful reversal is therefore a reason to observe, not to discharge.
Exam traps
Tolerance is selective
It develops to nausea and sedation but not to constipation or miosis. Questions test whether you expect the laxative to become unnecessary; it does not.
Codeine is a prodrug
CYP2D6 poor metabolisers get little analgesia and ultra-rapid metabolisers can reach toxic morphine levels from a standard dose.
Tramadol is not a plain opioid
Its monoamine reuptake inhibition brings serotonin syndrome and seizure risk that pure mu agonists do not carry.
Test yourself on this
Reading a mechanism and being able to retrieve it under time are different skills, and only the second one is examined. These are free and need no account.
- CNS pharmacology practice questions — 10 questions with explanations
- Morphine vs codeine and CYP2D6
- Opioid constipation and PAMORAs
- CYP450 inducers and inhibitors
- Creatinine clearance calculator (Cockcroft-Gault) — free calculator with a worked example
- mg/kg dose calculator — free calculator with a worked example
Common questions
Why does opioid constipation not go away?
Tolerance develops at the central receptors responsible for sedation and nausea, but not at the mu receptors in the gut wall. Motility stays suppressed for as long as the opioid is taken, which is why laxatives are continued alongside rather than stopped after the first week.
Why does codeine not work for some people?
Codeine has little activity itself and must be converted to morphine by CYP2D6. Genetic variation means poor metabolisers produce too little morphine for an effect, while ultra-rapid metabolisers can produce a dangerous amount.
How does naloxone work?
It competes with the opioid at the mu receptor without activating it, displacing the agonist and reversing respiratory depression. Because its half-life is shorter than many opioids, the patient must be observed for re-sedation.
Other drug classes
Beta blockers · ACE inhibitors · Statins · Anticoagulants · Diuretics · Benzodiazepines · All drug classes
Study aid only. This page is written for learning and examination practice. It is not medical advice, not clinical decision support, and must never be used to make a decision about a real patient. Always verify against your local formulary, the product literature and a qualified pharmacist. See our medical disclaimer.
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