A. Ordóñez Gallego

Oxycodone: a pharmacological and clinical review

Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma half-life is 3–5 h (half that of morphine) and stable plasma levels are reached within 24 h (2–7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone — which is also a very potent analgesic — and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5–2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3–4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin®) is marketed as 10-, 20-, 40-or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm®) is also available in capsules and oral solution. Side effects are those common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus and dizziness are less common. The intensity of these side effects tends to decrease over the course of time. Oxycodone causes somewhat less nausea, hallucinations and pruritus than morphine.

Cutaneous malignant melanoma and sun exposure in Spain.

Cutaneous malignant melanoma has an increasing importance all over the world. However very few epidemiological studies have been published from Spain, and Spanish people have not become aware of the problem. This study was designed to examine sun exposure patterns and other related items among 116 consecutive patients with melanoma and 235 controls. Each subject answered a questionnaire covering the place of residence, sun exposure details and other risk factors, and underwent a skin examination. Continuous sun exposure due to residence or occupation was associated with an odds ratio (OR) of 2.0 (95% confidence interval [CI] = 1.2-3.3). People who lived in the city but spent 50% of their time in rural areas for holidays had an OR of 2.2 (95% CI = 1.3-3.8) when compared with those living in urban and rural areas. The OR for people who sunbathed more than 30 times a year was 1.8 (95% CI = 1.2-2.8), and outdoor leisure time was also associated with melanoma appearance when exposure was greater than 60 units in the last 2 years, with an OR of 3.0 (95% CI = 1.6-5.5); 1 unit is equivalent to total body sun exposure for at least 2 h. These OR estimates were adjusted for age, skin type and the number of naevi. Construction workers (OR = 1.6; 95% CI = 0.5-5.6) had increased risk after adjustment for skin type, age and freckle count (OR = 4.3; 95% CI = 1.8 9.9) or mole count (OR = 2.8; 95% CI = 1.4-5.8). Working as a farmer was a protective factor after adjustment (OR = 0.5; 95% CI = 0.3-0.8). The use of sunscreens was a protective factor against melanoma (OR = 2.6; 95% CI = 1.6-3.6 for non-users). Campaigns should focus on advising people to avoid sun exposure in sunny places and to use sunscreens every time they are exposed to the sun.

Antiemetic Regimens in Outpatients Receiving Cisplatin and Non-Cisplatin Chemotherapy: A Randomized Trial Comparing High-Dose Metoclopramide Plus Methylprednisolone with and Without Lorazepam

Results of a randomized trial on antiemesis for cisplatin (CDDP) and non-CDDP chemotherapy-induced vomiting are reported. One hundred and sixty-three outpatients received 282 chemotherapy courses (141 with CDDP and 141 without CDDP). Patients were randomly assigned to receive either high-dose metoclopramide plus methylprednisolone (arm A) or the same drugs plus lorazepam (arm B). In both arms a high protection rate for vomiting was obtained, on the whole without statistically significant differences. Patients who received lorazepam had, however, significantly fewer nausea episodes during first day post-chemotherapy (p less than 0.05). Arm B was also superior in anxiety control during the first day of chemotherapy (p less than 0.01). Both regimens were significantly more effective in patients who had not been given chemotherapy previously (p less than 0.01). No differences in antiemetic protection were found between CDDP and non-CDDP courses. No significant differences were found in premonitory vomiting control between the two arms of the trial. Toxicity was very mild with both regimens, although sedation was significantly higher in arm B (p less than 0.001). We conclude that high-dose metoclopramide plus methylprednisolone is a highly effective combination for chemotherapy-induced nausea and vomiting, and that it is quite suitable for outpatient use. Lorazepam did not significantly increase the antiemetic potency of the combination, nor did it improve premonitory vomiting control, although it gave a better control of acute nausea and anxiety.

Neumomediastino como complicacion en la evolucion de la enfermedad de hodgkin. A proposito de un caso

Resumen Se presenta un paciente con enfermedad de Hodgkin, que a los ocho anos de evolucion y encontrandose en situacion casi terminal, tuvo como complicacion un neumodiastino secundario a una probable infiltracion linfomatosa y posterior desgarro del tercio distal esofagico. Aprovechamos el caso para exponer la etiopatogenia, clinica, radiologia y complicaciones del neumomediastino, asi como para intentar explicar lo insolito de esta complicacion.

Phase II Trial in Advanced Non-Small Cell Lung Cancer with Ifosfamide, Mitomycin and Cisplatinum

SummaryThe combination treatment using ifosfamide (4g/m2) with uroprotective mesna, mitomycin (6mg/m2), and cisplatinum (100mg/m2) (IMP) was evaluated in 51 patients with advanced non-small cell lung