Treating constipation in palliative care: the impact of other factors aside from opioids.

Opioids are major contributing factors to the problem of constipation in palliative care. Whilst this is without doubt, it remains unclear how much other factors also contribute to the problem. The aim of this audit is to review what other contributing factors are present when methylnaltrexone, the peripheral opioid antagonist is prescribed for constipation. The medical records of people prescribed methylnaltrexone over a four-month period were reviewed to examine certain characteristics of people including the whether the reason for constipation was charted, whether other factors that could contribute to constipation were considered and the effectiveness of methylnaltrexone. Over the study period, 10 people received methylnaltrexone, only 4 of whom had a bowel action less than 24 hours after administration with 3 not having any bowel actions reported 6 days after administration. Whilst all were receiving opioids, the opioids doses were in the moderate range (61-200 mg morphine equivalent). However, all had other factors that could contribute to constipation including impaired functional status and medications with anti-cholinergic effects (mean anti-cholinergic load 4.5). In conclusion, methylnaltrexone is targeted treatment for the management of opioid-induced constipation. However, there is a percentage of people who fail to respond. The impact of other factors on the problem of constipation requires greater clarification.

Interpretation of serum digoxin values in renal failure.

We have studied three circumstances that have been reported to make interpretation of the serum digoxin concentration difficult in patients with renal failure: increased biotransformation; endogenous digitalis-like factors (DLF); and sudden, unexpected increases in serum digoxin values, even after the discontinuation of digoxin. Biotransformation, as estimated by the percent true digoxin in serum, was comparable in patients with renal failure who were dependent on dialysis and in control subjects (76% vs. 73%). Certain commercial immunoassays did not, or rarely, gave values for DLF of clinical significance (greater than 0.2 ng/ml digoxin equivalents) in patients with a wide range of renal dysfunction who were not receiving digoxin. With a sensitive method, values for DLF did not exceed 0.23 ng/ml in 22 dialysis patients dependent on dialysis, but were significantly increased in comparison with values in control subjects. The case histories of two patients with renal failure, acute illness, and sudden unexpected marked increases in serum digoxin concentrations are presented and possible explanations are discussed.

Combined liquid chromatography/radioimmunoassay with improved specificity for serum digoxin.

This method for assaying digoxin in serum with improved specificity combines small-column extraction of serum, "high-performance" liquid chromatography, and RIA of the eluted fractions. Analytical recoveries of 1.0, 0.5, and 0.1 microgram/L standards were 95%, 93%, and 84%, respectively. The CVs for duplicates and replicates of sera with values of 0.5 to 1 microgram/L were 4 to 6%. Fifty-nine sera from 50 patients receiving digoxin were so studied. All digoxin metabolites appear to cross react with antibody to digoxin to various degrees. The most polar metabolites were quantitatively the most important, their average cross reactivity being 33%. For eight patients the value for digoxin by the present method was less than 60% of the RIA value. Sera from nine patients not taking digoxin but with falsely high digoxin values were also studied by the present method. The digoxin peak was well resolved from those for (a) digoxin metabolites (except dihydrodigoxin), (b) digitalis-like factors in neonates and in patients with renal failure or combined hepatic and renal failure, and (c) two cross reacting drugs and their metabolites.

The influence of dentofacial appearance on the social attractiveness of young adults.

The purpose of the study was to determine whether the social attractiveness of a young adult would be influenced by his or her dentofacial appearance. Black and white photographs of an attractive male, an unattractive male, an attractive female, and an unattractive female were obtained and modified so that, for each face, five different photographic versions were available. In each version, the face was standardized except that a different dentofacial arrangement was demonstrated. These were normal incisors, prominent incisors, absence of upper left lateral incisor, severely crowded incisors, and unilateral cleft lip. Eight hundred young adults were shown one of the twenty photographs and asked to estimate the represented individual's social characteristics along a number of bipolar scales. Each photograph was viewed by a different group of forty young adults, equally divided as to sex. Their impressions of the depicted individuals' social attractiveness were recorded on visual analogue scales. The experimental procedure was such that the effect and interaction of different levels of facial attractiveness, different dentofacial arrangements, sex of the photographed individual, and sex of the judge could be analyzed. Faces displaying a normal incisor relationship gained the most favorable ratings for eight of the ten characteristics examined, and in four of these differences across the range of dental conditions were statistically significant. These were perceived friendliness, social class, popularity, and intelligence. The prominent incisor condition was rated highest for compliance and honesty, while the condition representing a unilateral cleft consistently attracted low ratings. Background facial attractiveness of either the male or female stimuli was often more assertive than the individual dental condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Digoxin-rifampin interaction.

Digoxin doses required to maintain therapeutic serum concentrations rose substantially in two patients dependent on dialysis with the commencement of rifampin therapy. When rifampin was discontinued, doses fell to requirements before rifampin. Serum digoxin concentration may fall to ineffective levels with rifampin therapy and rise to potentially toxic levels when rifampin is discontinued.

Digoxin biotransformation.

Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis-dependent patients with end-stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 muCi 3H-digoxin-12 alpha. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3 beta-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3 alpha(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end-metabolites.

Digoxigenin biotransformation.

Two healthy subjects took 3H-digoxigenin-12 alpha and unlabeled digoxigenin. Metabolites were assayed by high-pressure liquid chromatography (HPLC) in serum and urine. Of the tritium activity in the serum at 30 min, less than 26% chromatographed with digoxigenin; the rest chromatographed as metabolites, most of which were polar. The main polar metabolites identified were glucuronides of 3-epidigoxigenin. An important route of biotransformation to polar metabolites appears to be from 3 beta-digoxigenin through 3-keto-digoxigenin to 3-epidigoxigenin. Several HPLC peaks remain unidentified. There was extensive cross reactivity between metabolites and antisera to digoxin. The digoxigenin route of digoxin biotransformation to polar metabolites may be important in some patients receiving digoxin and such metabolites could contribute an important fraction to the serum digoxin concentration measured by radioimmunoassay.