TeacherOfMedicine: Opioids, weak/moderate

For mild-to-moderate pain, including post-operative pain, as second-line agents when simple analgesics, such as paracetamol, are insufficient.
Weak opioids are on the second rung of the World Health Organization pain ladder.

In unmodified form, codeine and dihydrocodeine are very weak opioids.
They are metabolised in the liver to produce relatively small amounts of morphine (from codeine) or dihydromorphine (from dihydrocodeine).
These metabolites, which are stronger agonists of opioid µ (mu) receptors (see Opioids, strong), probably account for most of the analgesic effect.
About 10 of Caucasians have a less active form of the key metabolising enzyme (called cytochrome P450 2D6), and these people may find codeine and dihydrocodine largely ineffective.
Tramadol is a synthetic analogue of codeine; it is perhaps best classified as a ‘moderate’ strength opioid. Like codeine, tramadol and its active metabolite are µ-receptor agonists.
Unlike other opioids, tramadol also affects serotonergic and adrenergic pathways, where it is thought to act as a serotonin and noradrenaline reuptake inhibitor. This probably contributes to its analgesic effect.

Common side effects of weak opioids include nausea, constipation, dizziness and drowsiness. All opioids can cause neurological and respiratory depression when taken in overdose. Tramadol may cause less constipation and respiratory depression than other opioids. Codeine and dihydrocodeine must never be given intravenously, as this can cause a severe reaction similar to anaphylaxis. This is mediated by histamine release, but does not have an ‘allergic’ basis.

Caution must be exercised when prescribing an opioid in the context of significant respiratory disease. Tramadol, 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. Tramadol lowers the seizure threshold so is best avoided in patients with epilepsy, and certainly should not be used in those with uncontrolled epilepsy.

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. Tramadol should not be used with other drugs that lower the seizure threshold, such as serotonin-selective reuptake inhibitors and tricyclic antidepressants.

TeacherOfMedicine