Opioids Switching with Transdermal Systems in Chronic Cancer Pain

Background

Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy

Objective

To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.

Methods

A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks

Results

Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.

Conclusion

Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.     

Attending rounds

To determine attitudes regarding attending rounds, the authors surveyed all internal medicine residents and attending physicians at the eight Army teaching hospitals. The response rate was 86%, including 166 (76%) of 217 residents and 246 (93%) of 264 attendings. Of 12 educational activities, attending rounds were randked seventh by residents in their perceived value. Both residents and attendings favored sessions that lasted 90 minutes or less and were held three to four times per week. Most respondents felt case presentations should take 5 minutes or less and be delivered away from the patient’s bedside. On average, residents preferred less time at the bedside than did attendings (25% vs. 34% of attending round time). Residents desired substantial control of the agenda for rounds and also wanted to be responsible for one-third of the teaching. The attending-physician attributes that residents valued most highly were fund of knowledge, availability, and relating well to housestaff. Since residents’ and attending physicians’ attitudes may differ, expectations regarding attending rounds should be clarified at the beginning of a ward rotation so that mutually acceptable goals can be established. Presented in part at the 12th Annual Meeting of the Society of General Internal Medicine, Washington, D.C., April 28, 1989.     

Catabolism of chylomicron remnants in patients with previous acute pancreatitis

A recent study reports that patients with previous acute pancreatitis commonly have an abnormal clearance of serum triglycerides after an oral fat load. This observation supports the hypothesis that patients with previous acute pancreatitis and normal fasting serum triglyceride levels may have a preexistent abnormality in the metabolism of chylomicrons. To test this hypothesis, the catabolism of chylomicrons and their remnants was studied in a series of 7 patients who had sustained an attack of pancreatitis (2, gallstone related; 2, alcohol ingestion; 1, hydatid cyst; and 3, no associated pathological condition) at least 18 mo earlier. All the patients had previously had abnormal oral-fat tolerance test results. These patients were compared with a series of 6 healthy volunteers. Chylomicrons were endogenously labeled with an oral dose of retinyl palmitate, and their plasma elimination half-life was calculated. The retinyl palmitate absorption rate constants were similar in control and pancreatitis patients. The chylomicron t1/2 were 2.3 +/- 0.8 (SD) h and 3.9 +/- 1.8 h in the control and pancreatitis groups, respectively (p = 0.07). The chylomicron remnant t1/2 was 2.7 +/- 1.1 h in the control group and 5.2 +/- 2.4 h in the pancreatitis group (p less than 0.05). This study supports the hypothesis that subjects with previous acute pancreatitis may have an abnormality in the catabolism of chylomicron particles. This abnormality may represent a preexistent genetic condition expressed in either the apoprotein composition of chylomicrons or in the hepatic apolipoprotein E-receptor activity.     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis

Objectives.?To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle.

Patient and methods.?This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods.

Results.?Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle.

Conclusion.?Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.