Dihydrocodeine adverse effects

Codeine,oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. 

Mr A has been taking dihydrocodeine (as part of co-dydramol), one of the adverse effects of which is constipation. 

A modified-release formulation extends the duration of action of dihydrocodeine from 2-4 hours to 12 hours. In 12 volunteers who took modified-release dihydrocodeine 60 mg or 120 mg and 120 minutes later lactulose 40 mg diluted in 100 mg of water, the orocecal transit time was significantly prolonged by dihydrocodeine compared with placebo (5). Dihydrocodeine also significantly suppressed the pupillary light reflex. Both dosages caused similar adverse effects. Tiredness and dry mouth were reported in 80%, vertigo in 5%, and headache in 1%. 

Tramadol and non-steroidal anti-inflammatory drugs have been compared in two studies of patients with joint pain associated with osteoarthritis (8,9). In an open, randomized study 60 patients with osteoarthritis taking NSAIDs were given either modified-release tramadol 100 mg 8-hourly or modified-release dihydrocodeine 60 mg 8-hourly for 4 days the controls were 30 patients who took an NSAID alone (8). Both opioids provided adequate analgesic adjuncts to NSAIDs, but tramadol caused significantly more minor initial adverse effects. 

The absolute bioavailability of only a few drug compounds is affected by ESKD. An increase in bioavailability as the result of a decrease in metabolism during the drug s firstpass through the gastrointestinal tract and liver has been noted for some /3-blockers (i.e., bufu-ralol, oxprenolol, propranolol, and tolamolol), dextropropoxyphene, and dihydrocodeine. Although the bioavailability of these compounds is increased, clinical consequences (development of excessive or unexpected adverse effects) have only been demonstrated with dextropropoxyphene and dihydrocodeine. The lack of association between the pharmacokinetic profile and clinical consequences of the /3-blockers may result from an alteration in the responsiveness of patients with renal disease to these agents, as has been reported with propranolol in the elderly. ... 

The manufacturer states that nefopam should not be given to patients taking non-selective MAOIs and caution should be used in those taking tricyclic antidepressants, antimuscarinics and sym-pathomimetics. The intensity and incidence of adverse effects are somewhat increased when nefopam is given with codeine, pentazocine or dextropropoxyphene (propoxyphene), and the CNS depressant effect of dihydrocodeine may have contributed to a fatal overdose with nefopam. However, a morphine-sparing effect has been reported. Nefopam may also have a synergistic analgesic effect with ketoprofen. 

It is known, however, that drugs are readily available in many prisons, and the rate of adverse incidents and the time and effort spent in detecting smuggling of drugs in has been enough to persuade some authorities that at least the basics of treatment should be available. The most routine option has become to provide a detoxification for opiate misusers, with for instance lofexidine or dihydrocodeine, and also benzodiazepines will often be issued if there is a history of abuse of these and it is intended to avoid the possibility of fits with a short withdrawal course. The adverse incidents in custody and prisons have included some deaths in users of crack cocaine, with physical explanations postulated but no very satisfactory treatment for cocaine withdrawal indicated. Prison services have typically been wary of methadone, and in favouring lofexidine use it was encouraging that a randomized double-blind trial carried out by prison specialists found lofexidine to be as effective as methadone in relief of withdrawal symptoms (Howells et al. 2002). 

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