Codeine adverse effects

Few studies have explored the efficacy of opioids specifically for OA. The APS recommends against the use of codeine and propoxyphene for OA because of the high incidence of adverse effects and limited analgesic effectiveness. Oxycodone is the most extensively studied of the agents recommended for OA. However, other narcotic analgesics such as morphine, hydromorphone, methadone, and transdermal fentanyl are also effective. 

Adverse effects and drug interactions with codeine are similar to those reported for morphine, although they are less intense. Overdose in children results in the same effects as overdose of morphine, such as respiratory depression, miosis, and coma these symptoms are treated with naloxone administration. 

Codeine, which is an opium alkaloid is most commonly opiate used as antitussive and more selective for cough centre. Like morphine, it depresses cough centre but is less constipating and abuse liability is low. It is relatively safe drug used in cough along with analgesic property and it s only important adverse effect is constipation. 

As a result, these subjects require twofold to threefold higher daily doses of nortriptyline (a 2D6 substrate) to achieve therapeutic plasma levels. Conversely, in these ultrarapid-metabolizing populations, the prodrug codeine (another 2D6 substrate) is metabolized much faster to morphine, often resulting in undesirable adverse effects of morphine, such as abdominal pain. 

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. 

Some of the commonly used antitussives are listed in Table 26-1. As shown in the table, codeine and similar opiate derivatives suppress the cough reflex by a central inhibitory effect.21,124 Other nonopioid antitussives work by inhibiting the irritant effects of histamine on the respiratory mucosa or by a local anesthetic action on the respiratory epithelium. The primary adverse effect associated with most antitussives is sedation. Dizziness and gastrointestinal upset may also occur. 

The opioid derivatives most commonly used as antitussives are dextromethorphan, codeine, levopropoxyphene, and noscapine (levopropoxyphene and noscapine are not available in the USA). While these agents (other than codeine) are largely free of the adverse effects associated with the opioids, they should be used with caution in patients taking monoamine oxide (MAO) inhibitors (see Table 31-5). Antitussive preparations usually also contain expectorants to thin and liquefy respiratory secretions. 

Persons who drive or who are engaged in skilled work should avoid using codeine phosphate and alcohol together since they are incompatible and lead to seizures and adverse effects.39... 

Azipranone is a cough suppressant claimed to have effects comparable to those of codeine (1). Limited evidence suggests that its adverse effects are no different from those of placebo (SEDA-9,157). 

Data on the incidence of adverse effects after usual doses of oral ciramadol are conflicting. In one study there was a low incidence of mild adverse effects (1), but in another, in which ciramadol 60 mg was more effective than codeine 60 mg or placebo, there was a high incidence of opioid adverse effects (2) some other workers have had the same experience. 

The pharmacodynamic and adverse effects of codeine are mainly due to O-demethylation by CYP2D6 to morphine or a metabolite of morphine (SEDA-21, 86) (SEDA-22, 5). Poor metabolizers may lack the analgesic effect of codeine. 

A 20-year-old woman, who had previously taken paracetamol without adverse effects, took paracetamol 1 g and codeine 60 mg for a headache. After 3 hours she developed severe upper abdominal pain radiating to the back. The abdominal pain resolved within 24 hours of the administration of phloroglucinol and tiemonium. Her serum amylase activity was raised 3-fold and the serum lipase 15-fold. Other biochemical parameters, abdominal ultrasound, and an MRI scan were normal. Contrast-enhanced computed tomography showed pancreatic edema. 

In a comparison of the adverse effects of 30, 60, and 90 mg codeine the most freqnent adverse effects, headache, drowsiness, nausea, thirst, and a feehng of strangeness, occurred after 60 and 90 mg doses only. Visuomotor co-ordination was altered with 60 and 90 mg and dynamic visual acuity with 90 mg only (15). 

Conorfone is an opioid analgesic, a codeine derivative, with mixed agonist-antagonist activity (SED-11, 150). It has adverse effects similar to those of codeine, bnt canses more drowsiness (1). 

The use of opioids in very young patients is increasing. In a review of pain management in children, various routes of administration of opioids and their associated adverse effects have been discussed (SEDA-17, 78). Attention has been drawn to the adverse effects of intravenous codeine in children and to the risk of convulsions with pethidine in neonates, because of accumulation of its metabolite norpethidine. The risk of respiratory depression with morphine was also highlighted, and morphine is recommended for use only in neonates who are being ventilated or intensively nursed. Routine use of pulse oximetry has been recommended in all children receiving opioids (SEDA-21, 86). 

Some analgesics, such as codeine and dihydrucodeine. arc letcs potent than morphine and cannot be given in e<)uiana]gc jc doses because of the onset of adverse effects. As a result of this restriction in dosage, they are less likely, in practice, lo produce respiratory... 

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. 

Ketoprofen reduced morphine-associated respiratory depression, and did not alter morphine pharmacokinetics. Similarly, diclofenac did not alter morphine pharmacokinetics in one study. Improved pain relief and reduced adverse effects have been found when morphine was given with lomoxicam, ketoprofen, or ketorolac. However, in another, diclofenac slightly increased respiratory depression despite reducing morphine use, possibly because of persistent levels of an active metabolite of morphine. Diclofenac did not affect the pharmacokinetics or analgesic effects of codeine in healthy subjects. Intramuscular diclofenac did not affect the pharmacokinetics of methadone solution in cancer patients. Ibuprofen did not appear to interact... 

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