TeacherOfMedicine: Opioids, compound preparations

Mild-to-moderate pain: as second-line agents when simple analgesics, such as paracetamol, are insufficient. Co-codamol and co-dydramol are on the second ‘rung’ of the World Health Organization (WHO) ‘pain ladder’.

The mechanism of action of paracetamol is poorly understood.
Paracetamol is a weak inhibitor of cyclooxygenase (COX), the enzyme involved in prostaglandin metabolism. In the central nervous system, COX inhibition appears to increase the pain threshold.
Codeine and dihydrocodeine are weak opioids. They are metabolised by cytochrome P450 enzymes to morphine and morphine-related metabolites. These metabolites, which are agonists of opioid µ-receptors, probably account for most of their analgesic effect (see Opioids, strong).
Combining two analgesics with different mechanisms of action may offer better pain control than can be achieved with either drug alone. Putting them together in a fixed-ratio compound product improves convenience for the patient, although at a cost of reduced flexibility in terms of dose titration.

When taken at recommended doses, adverse effects from paracetamol are rare.
Common side effects of codeine and dihydrocodeine include nausea, constipation and drowsiness.
In overdose the effects of both paracetamol (principally hepatotoxocity) and opioid toxicity (neurological and respiratory depression) may be evident.

Caution must be exercised when prescribing an opioid in the context of significant respiratory disease.
Codeine and dihydrocodeine rely on both the liver and the kidneys for their elimination. Doses should therefore be reduced in renal impairment and hepatic impairment, and also in the elderly.

Opioids should ideally not be used with other sedating drugs (e.g. antipsychotics, benzodiazepines and tricyclic antidepressants). Where their combination is unavoidable, closer monitoring is necessary.

TeacherOfMedicine