Codeine antitussive action

Codeine, dextromethorphan and pholcodine are opioid cough suppressants indicated for dry cough. Sedating antihistamines, such as diphenhydramine, tend to have an antitussive action as well. Vitamin C is not used in the management of cough but may be used as a prophylaxis against colds. 

Codeine, as noted, has a useful antitussive action at doses lower than those required for analgesia. Thus, 15 mg are usually sufficient to relieve cough. 

Noscapine resembles papaverine in its action on smooth muscle and, in large doses, induces bronchodilation in animals. It is readily absorbed from the gastrointestinal tract, but its metabolic fate is unknown. In experimentally induced cough in animals and humans, noscapine exerts an antitussive action approximately equal to that of codeine, without any of the unpleasant side effects of codeine. It is administered orally in doses of 15 to 30 mg, three or four times daily as an antitussive. 

Antitussive action—independent of analgesia (e.g., dextromethorphan) and at subanalgesic doses with codeine. 

CODEINE In contrast to morphine, codeine is -60% as effective orally as parenteraUy as an analgesic and as a respiratory depressant. Codeine analogs such as levorphanol, oxycodone, and methadone have a high ratio of oral-to-parenteral potency. The greater oral efficacy of these drugs reflects lower first-pass metabolism. Once absorbed, codeine is metaboUzed by the liver, and its metabolites are excreted chiefly as inactive forms in the urine. A relatively small fraction (-10%) of administered codeine is O-demethylated to morphine, and free and conjugated morphine can be found in the urine after therapeutic doses of codeine. Codeine has an exceptionally low affinity for opioid receptors, and the analgesic effect of codeine is due to its conversion to morphine. However, its antitussive actions may involve distinct receptors that bind codeine itself. The tj of codeine in plasma is 2-4 hours. 

Dextromethorphan HBr is the ( + )-isomer of the 3-methoxy form of the synthetic opioid levorphanol. It lacks the analgesic, respiratory depressant, and abuse potential of p opioid agonists but retains the centrally acting antitussive action. Dextromethorphan is not an opioid and is not listed in the Controlled Substances Act. Its effectiveness as an antitussive is less than that of codeine. Dextromethorphan is available in a number of nonprescription cough formulations. 

Opioid receptors have also been located in the periphery, bnt their ability to exert considerable antitussive action at this level is debatable. Aerosol administration of codeine is not antitussive in hnmans challenged with capsaicin (Kamei 2002), and althongh the peripherally acting peptide BW443C is antitnssive in animal stndies (Adcock et al. 1988), there is only limited clinical evidence to snpport this antitnssive effect in humans (Pavord et al. 1994). 

Nonnarcotic Antitussives. The most centrally active, noimarcotic antitussive is dextromethorphan [125-71-3] (39). It is similar to codeine in terms of potency and mechanism of action, ie, it is a direct depressant of the cough center. It is unique in that even though it is stmcturaHy related to codeine, it is not addictive. 

Dextromethorphan is an opioid antitussive similar in action to codeine and pholcodine. Codeine and pholcodine are considered to be more potent than dextromethorphan. Dextromethorphan tends to cause less constipation and dependence than codeine. Cough suppressants are not usually recommended in children under 2 years. 

Pharmacology Dextromethorphan is the d-isomer of the codeine analog of levorphanol. Its cough suppressant action is due to a central action on the cough center in the medulla. Dextromethorphan 15 to 30 mg equals 8 to 15 mg codeine as an antitussive. 

Dextromethorphan is the dextrorotatory stereoisomer of a methylated derivative of levorphanol. It is purported to be free of addictive properties and produces less constipation than codeine. The usual antitussive dose is 15-30 mg three or four times daily. It is available in many over-the-counter products. Dextromethorphan has also been found to enhance the analgesic action of morphine and presumably other -receptor agonists. However, abuse of its purified (powdered) form has been reported to lead to serious adverse events including death. 

Analgesic efficacy and clinical use Codeine (Honig and Murray, 1984) has a morphine-like action profile with analgesic and antitussive properties. As compared to morphine the analgesic potency is 5—1 Ofold lower. The compound is used for the treatment of mild to moderate pain and for cough inhibition (Eccles,1996). 

Analgesic efficacy and medical use Ethylmorphine has an action profile similar to codeine with analgesic, antitussive and antidiarrheal properties. It has been used in similar circumstances to codeine as a cough suppressant and analgesic, but today it is mostly out of use. 

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. 

Ethylmorphine hydrochloride (Dionine ) resembles codeine more closely in its action than it does morphine. It is used primarily as a chemotic to produce vasodilatation and edema of the conjunctiva in corneal ulcer and other inflammatory conditions of the eye. For this purpose, it is instilled topically as a 1 to 5% solution in the eye. It has also been used as an antitussive in doses of 15 mg. 

Morphine has been, and remains, an important drug even though codeine is used to a larger extent than morphine and, while its analgesic action is only one-sixth of morphine, it is employed for its antitussive effect, as a cough repressant. 

Dextromethorphan hydrobromide is an antitussive drug with no analgesic or addictive action. Its antitussive effect is similar to codeine. The recommended oral dose for adults is 10-30mg three to six times a day, not to exceed 120mg daily. It is absorbed rapidly and completely when taken orally with a lag time of 15-30 min [72]. 

N-oxides of morphine and several morphine derivatives have been prepared by the action of isopropanol/H202 on the appropriate tertiary base.(156) At best, the N-oxides were weak analgesics, but dihydromorphinone N-oxide and codeine N-oxide did exhibit good antitussive properties/157 ... 

---