Codeine clinical

Noyes R, Brunk SF, Avery DAH and Canter AC (1975b). The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapeutics, 18, 84-89. 

Molecular modifications of the morphine skeleton have produced numerous derivatives with antitussive properties, some of which have become commercially significant. Ethyknorphine [76-58-4] (29), a simple homologue of codeine, is prepared by ethylating morphine. It is pharmacologically similar to codeine but is seldom used clinically. Pholcodine [509-67-1] (30), the morpholinoethyl derivative of morphine, is used as an antitussive in a number of European countries. It is about one and a half times as potent as codeine, has Htde or no analgesic activity, and produces minimal physical dependence. The compound is prepared by the amino alkylation of morphine (48). 

Dihydrocodeine [125-28-0] (33), introduced in Germany before 1930, and dihydrocodeinone enol acetate [466-90-0] (34) both have clinical activity and addiction potential comparable to codeine. 

Levopropoxyphene [2338-37-6] (42), the optical antipode of the dextrorotatory analgetic propoxyphene, is an antitussive without analgetic activity. The 2-naphthalenesulfonate salt has a less unpleasant taste than the hydrochloride salt, and is widely used. Clinical effectiveness has been demonstrated against pathological and artificially induced cough, but the potency is somewhat less than codeine. The compound is reported not to cause addiction. Levopropoxyphene can be prepared (62) by first resolving [ -dimethylamino-CX-methylpropiophenone with dibenzoyl-(+)-tartaric acid. The resolved... 

The citrate salt of isoaminile [77-51-0] (50) is a nitrile used as an antitussive in numerous European countries. In clinical trials it was shown to be as effective as codeine or chlophedianol, with few mild side effects. Isoaminile citrate is longer acting than chlophedianol and does not cause the respiratory depression of codeine (68). 

Diphenhydramine [58-73-1] (55) was originally developed as an antihistamine and was first used clinically for this purpose in 1946 (see HiSTAMlNE AND HISTAMINE antagonists). In addition to this primary effect, however, central antitussive activity has also been demonstrated in animals (75,76) and in humans (77). Its antitussive activity is about half that of codeine. Drowsiness is the most frequent side effect. Diphenhydramine can be prepared as follows (78) ... 

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). 

Pharmacological clinical activity bias. An AE that is already present due to the disease may be increased if it is also an ADR of the drug or vice versa. For example, the diarrhea of gastroenteritis may be alleviated by codein-containing preparations given to relieve pain while the inertia of a severely depressed patient may be sufficiently resolved by an antidepressant to enable the patient to commit suicide. 

The clinical analgesic efficacy of THC is prominent. In a study of cancer patients, 10 mg of THC was equivalent to 60 mg of codeine (Noyes et al. 1975). This dose produced sedative but no other psychoactive effects. A dose of 20 mg was more effective, but produced additional dizziness, ataxia, blurred vision, and psychoactive effects. 

The above mentioned reactions are widely used in alkaloid modification. A good example of alkaloid modifications for clinical curation purposes are opioides. Morphine and codeine are natural products of Papaver somniferum. However, the codeine is naturally produced in small amounts. This is one reason why it is produced synthetically from morphine by modification. As codeine is the 3-0-methyl ether of morphine, the mono-O-methylation occurs in the acidic phenolic hydroxyl. Pholcodine is obtained by modification of morphine through alkylation with A-(chloroethyl)morpholine. Moreover, dihydrocodeine, hydro-morphone and heroine are also obtained from morphine through modifications. 

The most known narcotics are the opium alkaloids such as morphine, codeine, thebaine, papaverine, noscapine and their derivatives and modified compounds such as nalmorphine, apomorphine, apomopholcodine, dihydrocodeine, hydro-morphone and heroine, also known as diamorphine. Synthetic narcotics share the structural skeleton of morphine and include dextromethorphan, pentazocine, phenazocine meperidine (pethidine), phentanyl, anfentaitil, remifentalin, methadone, dextropropoxyphene, levoproxyphene, dipipanone, dextromoramide, meptazinol and tramadol. Thebaine derivatives are also modified narcotics and include oxycodone, oxymorphone, etorphine, buprenorphine, nalbuphine, naloxone or naltrexone. Narcotics can be semi-synthesized or totally synthesized from the morphine and thebaine model. The compounds serve various purposes in clinical practise. 

Alkaloids such as boldine, codeine, narceine and morphine are also important in clinical practice. Boldosal and Oxyboldine are good examples of boldine-based drugs with morphine-like properties. 

On day 4, the patient began to lose consciousness and he became unresponsive. His last dose of codeine was 12 hours earlier. The patient was hypoxemic and was ventilated to improve his oxygen tissue levels. Clinical examination revealed pinpoint pupils, no eye opening, and no verbal response. 

The adventitious discovery, in prehistory, of the analgesic soporific and the euphoriant properties of the dried sap from the flower bulb of the poppy, papaver somnifemm, has been treated too often elsewhere to warrant repetition. By the nineteenth century organic chemistry had advanced far enough so that the active principle from opium had been isolated, purified, and crystallized. Increasing clinical use of this compound, morphine (1-1), and its naturally occurring methyl ether codeine (1-2) disclosed a host of side effects, the most daunting of which was, and stUl is, these compounds propensity for inducing physical dependence. 

Clinical use Phenidine (Clissold, 1986) is a weak analgesic and antipyretic compound without antiinflammatory action. It has been used in combination with other compounds like aspirin, caffeine or codeine, but due to hematological and nephrotoxic side-effects (Dubach et al., 1983) has been withdrawn from many markets. 

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). 

A9-THC is marketed as marinol or dronabinol for the treatment of chemotherapy-induced nausea and vomiting in Australia, Canada, Israel, South Africa and the USA. It was granted orphan drug status in the US for the stimulation of appetite and prevention of weight loss in patients with a confirmed diagnosis of AIDS. A9-THC is in phase I trials for spasticity, multiple sclerosis and postoperative pain. Several small clinical studies have confirmed the effectiveness of A9-THC as an analgesic, with doses of 15 to 20 mg being comparable to 60 to 120 mg of codeine (Williamson and Evans, 2000). 

---