Codeine pharmacological effects

Hydrocodone (Hycodan), oxycodone (Roxicodone), dihydrocodeine, hydromorphone (Dilaudid), and oxy-morphone (Numorphan) are derivatives of codeine and morphine. All are indicated for the relief of mild to severe pain or for their antipyretic effects they are often used in combination with nonopioid analgesics. The drugs vary in potency, but their pharmacological effects do not differ significantly from those of codeine or morphine. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

These naturally occurring nitrogen-containing chemicals (amines) have very diverse in pharmacological effects. Examples include codeine, morphine, caffeine, and emetine. 

This paper presents a mass spectral study of impurities in illicit heroin. Identification of these impurities is of importance because of their potential contribution to pharmacological effects. The major impurities, 6-acetyl-morphine ( -c) and 6-acetylcodeine ( I-k), are predictable, owing to their origination from the naturally-occurring alkaloids-morphine ( -a) and codeine (r-j)(l) after reaction with acetic anhydride. In addition, the presence of a trace impurity (m/e 397, C22H23NO0, at less than 0.4%) was observed by gas chromatography-mass spectrometry (Fig. 2). 

The pharmacological effects of this complex mixture of alkaloids in opium may, in some respects, be more beneficial than the effects of an individual alkaloid. The effect of opium in the treatment of diarrhoea is better than that of either morphine or codeine given individually. It is possible to calm the gastrointestinal tract with a dose which contains only half of the dose which would be necessary for morphine alone. The combination of the increase in stretch reflex caused by morphine and the inhibition of increased peristaltic action by papaverine leads to a better therapeutic effect. The increase in muscle tone due to morphine is reduced by papaverine, and other benzylisoquinolines also participate in this tranquillisation of the g.i. tract. In the normal 50 mg dosage of opium used for the treatment of diarrhoea there is about 5 mg of morphine, 0.5 mg of papaverine and 3 mg of nos-capine which contrasts markedly with a dose of 100—200 mg of papaverine if this were given alone. The analgaesic activity of opium is due mainly to the morphine present, as the levels of codeine, neopine and papaverine are relatively small. The respiratory depression effect of opium is also due to the morphine content and the antagonistic effects of noscapine and narcotoline are not so pronounced. Thus the main use of opium in medicine is for the treatment of diarrhoea. 

Oxolamine [959-14-8] (57) is sold in Europe. It is an oxadiazole, and its general pharmacological profile is described (81). The compound possesses analgesic, antiinflammatory, local anesthetic, and antispasmodic properties, in addition to its antitussive activity. Although a central mechanism may account for some of the activity, peripheral inhibition of the cough reflex may be the dominant effect. The compound has been shown to be clinically effective, although it is less active than codeine (82,83). The synthesis of oxolamine is described (84). 

Together, the chemistry of codeine and the drug s absorption into the bloodstream, distribution to various compartments and tissues in the body, metabolism (breakdown of the parent compound into smaller molecules, or metabolites), and excretion are intimately related to how codeine exerts its medicinal or therapeutic effects. Codeine s chemical properties and pharmacologic characteristics explain how, figuratively speaking, a spoonful of codeine can relieve pain, suppress cough, or act as an antidiarrheal. 

The medicinal chemistry and pharmacology of codeine can also shed light on why specific side effects (the unintended, undesirable, and unwanted effects) associated with codeine occur. Codeine s side effects, or toxicities, are discussed in the next chapter. 

Darvon , d-propoxyphene hydrochloride, is a synthetic, nonantipyritic, orally effective analgesic, with similar pharmacological activity and effects to codeine. Darvon is not a narcotic but can be substituted for codeine, and is useful in any condition associated with pain. Chemically, this analgesic is not analogous to codeine or to morphine. 

Renal insufficiency can result in clinically significant accumulation of pharmacologically active opioid metabolites and prolonged narcosis such patients must be monitored for signs of toxicity (SEDA-17, 79) (SEDA-21, 85) (98,99). To date, this effect has only been reported with codeine, morphine, and pethidine. Dextropropoxyphene is not recommended in renal insufficiency, as its metabolite norpropoxyphene, which is eliminated by the kidneys, accumulates, causing cardiac depression (SEDA-17, 79) (SEDA-21, 85). 

Tile general pharmacological action of codeine is similar 10 that of morphine, but as indicated above, it does not possess the same analgesic potency. Studies indicate that a dose uf. fO to 120 mg of ctxleinc is considerably less efficient uninterally than 10 mg of morphine, and the usual side effects of morphine—respiratory depression, constipation, nausea, and such—occur. Codeine is less effective orally lhan pareiitemlly, and Houde and Wallenstein stated that a do.se of. 52 mg of codeine is about as effective as 650 mg nf aspirin in relieving terminal cancer pain. Combinations... 

Long-term use of oral opiates is not routinely recommended for several pharmacologic reasons. Some opioids such as morphine and codeine have the tendency to cause constipation by slowing down the peristaltic action of the bowels, which can also result in a functional ileus. This effect can be minimized by administering laxatives and/or stool softeners in patients who require longer-term opiate therapy. Prokinetic agents may also be helpful in treating opiate-related constipation. 

Codeine is an analgesic that is effective in the treatment of mild to moderate pain. It is often combined with other analgesic products and enjoys a popularity that makes it the standard for other oral opioids. Unfortunately, codeine has the same propensity to produce tolerance, dependence, and constipation as morphine. Hydrocodone, a derivative of codeine, also is seen most often in combination products and has pharmacologic properties similar to those of morphine. Oxycodone has a similar potency to morphine and is an excellent oral analgesic for moderate to severe pain. This is especially trne when the product is used in combination with nonopioids however, its predilection for causing tolerance and dependence, along with its basic opioid characteristics, likens it to morphine. It shonld be noted that sustained-release oxycodone is also available. 

Pharmacologic treatment of RLS includes dopaminergic agents, benzodiazepines, opioids, or anticonvulsants. In mild cases of RLS, benzodiazepines may be first-line agents. Clonazepam, lorazepam, triazolam, and temazepam have been effective. Clonazepam 0.5 to 2 mg is most frequently studied. Opiates such as methadone 5 to 20 mg, codeine 30 to 120 mg, and oxycodone 2.5 mg are very effective, but the development of tolerance is a concern. Abuse potential with opiates is also a concern due to the chronic nature of the condition. Other agents that have been used include apomorphine, amantadine, tramadol, magnesium, oxycodone, propoxyphene, gabapentin, bromocriptine, clonidine, and carbamazepine. Tolerance may de-... 

Conversely, the demonstration of an antitnssive effect in the laboratory does not imply that a pharmacological agent will prove efficacious in a patient population. The opioid narcotic codeine, for example, has been shown in some clinical trials to inhibit capsaicin-induced cough (Dicpinigaitis et al. 1997 Fuller et al. 1988), yet was ineffective against cough due to URTI (Freestone and Eccles 1997). 

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