Changes in trends and pattern of strong opioid prescribing in primary care.

BACKGROUND: This study evaluated the prescribing trends of four commonly prescribed strong opioids in primary care and explored utilization in non-cancer and cancer users. METHODS: This cross-sectional study was conducted from 2000 to 2010 using the UK Clinical Practice Research Datalink. Prescriptions of buprenorphine, fentanyl, morphine and oxycodone issued to adult patients were included in this study. Opioid prescriptions issued after patients had cancer medical codes were defined as cancer-related use; otherwise, they were considered non-cancer use. Annual number of prescriptions and patients, defined daily dose (DDD/1000 inhabitants/day) and oral morphine equivalent (OMEQ) dose were measured in repeat cross-sectional estimates. RESULTS: In total, there were 2,672,022 prescriptions (87.8% for non-cancer) of strong opioids for 178,692 users (59.9% female, 83.9% non-cancer, mean age 67.1 ± 17.0 years) during the study period. The mean annual (DDD/1000 inhabitants/day) was higher in the non-cancer group than in the cancer group for all four opioids; morphine (0.73 ± 0.28 vs. 0.12 ± 0.04), fentanyl (0.46 ± 0.29 vs. 0.06 ± 0.24), oxycodone (0.24 ± 0.19 vs. 0.038 ± 0.028) and buprenorphine (0.23 ± 0.15 vs. 0.008 ± 0.006). The highest proportion of patients were prescribed low opioid doses (OMEQ ≤ 50 mg/day) in both non-cancer (50.3%) and cancer (39.9%) groups, followed by the dose ranks of 51-100 mg/day (26.2% vs. 28.7%), 101-200 mg/day (15.1% vs. 19.2%) and >200 mg/day (8.25% vs. 12.1%). CONCLUSIONS: There has been a huge increase in strong opioid prescribing in the United Kingdom, with the majority of prescriptions for non-cancer pain. Morphine was the most frequently prescribed, but the utilization of oxycodone, buprenorphine and fentanyl increased markedly over time.

Cadralazine for the treatment of preeclampsia. An open, noncomparative, dose-finding pilot study.

The antihypertensive effect, tolerability, and influence on placental and fetal circulation of cadralazine, a 6-substituted derivative of 3-hydrazinopyridoxine structurally related to hydralazine, was assessed in 46 preeclamptic patients in the third trimester of pregnancy and with diastolic blood pressure of 100-120 mm Hg after 24 hours of bed rest. Patients who fulfilled the inclusion criteria at the initial report (24-48-hour run-in period after hospitalization) entered the titration period. During titration, cadralazine was administered at an initial dose of 5 mg once a day; if after 3 days diastolic blood pressure was still above 90 mm Hg, 5 mg more was added for another 3 days, and so forth, until the maximum dose (20 mg once a day) was reached. Patients who did not lower diastolic blood pressure below 90 mm Hg were considered nonresponders; those who achieved the desired diastolic level (responders) entered the maintenance period, which lasted until delivery. Eight patients delivered during the titration period (premature discontinuation group). A significant decrease in systolic and diastolic blood pressures was observed between the initial report and the titration period. During titration, there were 27 responders (71%) and 11 nonresponders. One of the responders was lost to follow-up. Cadralazine proved to be effective in lowering blood pressure levels; in the group of responders, a mean diastolic reduction of 20% was observed. This significant decrease was not affected by the diastolic blood pressure increase observed at the end of gestation. No adverse effects from the drug were observed on fetal development or immediate postnatal adaptation to stress during labor, and only mild maternal side effects were detected (headache).

Noninvasive ambulatory blood pressure control in normotensive pregnant women.

Twenty-four hour noninvasive, automatic and ambulatory control of blood pressure (BP) was carried out on 11 normotensive pregnant women in the third trimester of pregnancy with a Del Mar Avionics Model 1978 Pressurometer III System at 7.5 min intervals during 24 h. The patients kept a detailed record of their activities during those 24 h. BP increased from 9 AM to a peak between 7 and 10 PM. Mean (+/- SD) waking and sleeping values were 110.56 +/- 6.68 mm Hg and 96.5 +/- 10.01 mm Hg, respectively, for systolic BP, and 71.41 +/- 5.35 mm Hg and 62.82 +/- 5.47 mm Hg, respectively, for diastolic BP. There was a significant difference in systolic and diastolic BP between sleeping hours and waking hours. We believe that 24-h control of BP behavior in normotensive pregnant women allows us to adequately diagnose hypertensive disease in pregnancy.

Ketanserin versus alpha-methyldopa in the treatment of hypertension during pregnancy: a preliminary report.

The antihypertensive efficacy of acute treatment with the serotonin receptor antagonist, ketanserin, in women with preeclampsia has been recently documented. The purpose of this study was to determine the safety and efficacy of chronic ketanserin treatment in a group of 20 hypertensive pregnant women: 10 received daily oral doses of ketanserin (20-80 mg), and 10 were treated with oral alpha-methyldopa (500-2000 mg). This study includes (a) patients with a sustained elevation of systolic blood pressure higher than 159 mm Hg and/or diastolic blood pressure higher than 99 mm Hg at bed rest, and (b) hypertensive patients with systolic blood pressure higher than 140 mm Hg or diastolic blood pressure higher than 90 mm Hg with superimposed symptoms such as headaches, stomach aches, and neurological disturbances. A significant and comparable decrease in blood pressure was noted in both groups, in relation with pretreatment levels; no adverse affects were observed in mother or fetus from the ketanserin and alpha-methyldopa groups.

Evaluation of a new antihypertensive agent ketanserin versus methyldopa in the treatment of essential hypertension in older patients: an international multicenter trial.

The serotonergic antagonist ketanserin (K) was compared to methyldopa (M) in a four-center international study in 119 hypertensive patients over 50 years of age. After a 4-week placebo run-in period, patients randomly received K (20-40 mg b.i.d.) or M (250-500 mg b.i.d.) for 3 months. The drugs were given in monotherapy for at least 1 month, then a diuretic could be added if blood pressure remained abnormally high. For the patients on monotherapy, active drug was replaced by placebo at the end of the 3-month period until the patients were hypertensive again. K and M had a similar effect on systolic blood pressure, but diastolic blood pressure was reduced significantly more by K than by M. Significantly more patients had their blood pressure normalized in the K group (75%) than in the M group (49%). The twice daily dosage schedule caused trough blood pressure control with both drugs. No rebound hypertension occurred at discontinuation of treatment. Monotherapy with K caused a decrease in heart rate (-5 beats/min) while M produced no change. Body weight decreased with K (-0.5 kg) and increased with M (+ 0.4 kg). No important hematological or biochemical changes were seen with either drug. Slightly fewer patients reported adverse reactions during K monotherapy (40%) than with M (45%). In the latter group mainly central side effects were observed. The data confirm K to be an effective first-line antihypertensive agent with a favorable side-effect profile.