Methadone as Social Control: Institutionalized Stigma and the Prospect of Recovery

Methadone maintenance treatment (MMT) is an intervention used to treat opioid (heroin) dependence. Several investigators have found that MMT is effective in reducing heroin use and other behaviors; however, a disproportionate number of MMT clients leave treatment prematurely. Moreover, MMT outcome variables are often limited in terms of their measurement. Utilizing an integrated theoretical framework of social control and stigma, we focused on the experiences of methadone maintenance from the perspective of clients. We pooled interview data from four qualitative studies in two jurisdictions and found linkages between social control and institutional stigma that serve to reinforce "addict" identities, expose undeserving customers to the public gaze, and encourage clients to be passive recipients of treatment. We discuss the implications for recovery and suggest recommendations for change.

Contribution of process variables to the entrapment efficiency of propranolol hydrochloride within ethylcellulose microspheres prepared by the solvent evaporation method as evaluated using a factorial design

The effects of the process variables, pH of aqueous phase, rate of addition of organic, polymeric, drug-containing phase to aqueous phase, organic:aqueous phase volume ratio and aqueous phase temperature on the entrapment of propranolol hydrochloride in ethylcellulose (N4) microspheres prepared by the solvent evaporation method were examined using a factorial design. The observed range of drug entrapment was 1.43 +/- 0.02%w/w (pH 6, 25 degrees C, phase volume ratio 1:10, fast rate of addition) to 16.63 +/- 0.92%w/w (pH 9, 33 degrees C, phase volume ratio 1:10, slow rate of addition) which corresponded to mean entrapment efficiencies of 2.86 and 33.26, respectively. Increased pH, increased temperature and decreased rate of addition significantly enhanced entrapment efficiency. However, organic:aqueous phase volume ratio did not significantly affect drug entrapment. Statistical interactions were observed between pH and rate of addition, pH and temperature, and temperature and rate of addition. The observed interactions involving pH are suggested to be due to the abilities of increased temperature and slow rate of addition to sufficiently enhance the solubility of dichloromethane in the aqueous phase, which at pH 9, but not pH 6, allows partial polymer precipitation prior to drug partitioning into the aqueous phase. The interaction between temperature and rate of addition is due to the relative lack of effect of increased temperature on drug entrapment following slow rate of addition of the organic phase. In comparison to the effects of pH on drug entrapment, the contributions of the other physical factors examined were limited.

AN INVESTIGATION OF THE EFFECTS OF SOME PROCESS VARIABLES ON THE MICROENCAPSULATION OF PROPRANOLOL HYDROCHLORIDE BY THE SOLVENT EVAPORATION METHOD

The effects of four process factors: pH, emulsifier (gelatin) concentration, mixing and batch, on the % w/w entrapment of propranolol hydrochloride in ethylcellulose microcapsules prepared by the solvent evaporation process were examined using a factorial design. In this design the minimum % w/w entrapments of propranolol hydrochloride were observed whenever the external aqueous phase contained 1.5% w/v gelatin at pH 6.0 (0.71-0.91% w/w) whereas maximum entrapments occurred whenever the external aqueous phase was composed of 0.5% w/v gelatin at pH 9.0,(8.9-9.1% w/w). The theoretical maximum loading was 50% w/w. Statistical evaluation of the results by analysis of variance showed that emulsifer (gelatin) concentration and pH, but not mixing and batch significantly affected entrapment. An interaction between pH and gelatin concentration was observed in the factorial design which was accredited to the greater effect of gelatin concentration on % w/w entrapment at pH 9.0 than at pH 6.0. Maximum theoretical entrapment was achieved by increasing the pH of the external phase to 12.0. Marked increases in drug entrapment were observed whenever the pH of the external phase exceeded the pK(2) of propranolol hydrochloride. It was concluded that pH, and hence ionisation, was the greatest determinant of entrapment of propranolol hydrochloride into microcapsules prepared by the solvent evaporation process.

Survey of oral health behaviours of patients receiving methadone therapy at a drug rehabilitation centre

Background: This survey aimed to record the dietary habits and oral health behaviours of patients undergoing methadone maintenance therapy at a Scottish drug rehabilitation centre.The objectives were to obtain descriptive data for each of the participants on items including dietary habits, oral hygiene practices and dental health. The study also aimed to explore explanatory relationships between dietary habits, oral hygiene practices and dental health (DMFT) in methadone users.
Methods: A cross – sectional descriptive study using survey methodology was conducted of consecutive adult patients undergoing methadone maintenance therapy at a non-residential drug rehabilitation centre in Dundee, Scotland. A self-completion retrospective questionnaire was distributed to 66 consecutive patients.
Results: A response rate of 74.2% was achieved. Participants reported low daily intakes of fresh fruit and vegetables with diets high in fatty foods. Respondents reported regular snacking between meals and consumption of large amounts of sugared carbonated drinks. Oral hygiene practices were poorly adhered to and a high level of dental disease was observed amongst participants. Poisson regression analysis revealed that the amount of alcohol consumed per day (p=0.02), the length of time taking methadone (p=0.002) the amount of sugar added to hot drinks (p<0.0001) and regular dental attendance (p=0.0001) were all independently associated with poor dental health.
Conclusions: Dietary habits and adherence to oral hygiene practices amongst this group of patients were very poor. This study suggests that these behaviours were contributing to the high levels of dental disease observed in this group.

Dietary habits of patients undergoing methadone therapy

OBJECTIVE: This study was designed to record the dietary habits of patients undergoing methadone therapy.

BACKGROUND: Numerous studies report that patients undergoing methadone treatment present with high levels of oral disease, especially dental caries. A number of factors have been described to account for this: sugared methadone preparations, prolonged oral retention, associated xerostomia and poor diet.

METHODS: A cross-sectional descriptive study using survey methodology was conducted of patients attending a non-resident drug rehabilitation clinic. A self-completion questionnaire and diet diary were developed and distributed to 66 patients over an 8 week period.

RESULTS: Of the 66 questionnaires distributed, 52 were successfully completed giving a response rate of 79%. 6 patients declined to complete the questionnaire. The surveyed patient pool consisted of 32 females (62%) and 20 males (38%) with a mean age of 32 years. All the participants were taking a prescribed daily dose of methadone when questioned. 68% of respondents consumed convience foods or sugary snacks every day. Of those patients who drank tea or coffee daily, 84% added sugar and 54% added 3 teaspoons or more. The majority of patients (71%) consumed at least one glass of a fizzy soft drink daily. In addition, the majority of respondents indicated that they snacked regularly between meals and 24% stated that they often woke up during the night for a snack. Patients recorded their last intake of food ranging from 5pm to 3am.

CONCLUSIONS: The patients surveyed had poor dietary habits. Respondents consumed a large amount of convience foods and sugars during mealtimes and through regular snacking. Dietary counselling should be considered as part of treatment for patients undergoing methadone therapy.

An optimized reverse-phase high performance liquid chromatographic method for evaluating percutaneous absorption of glucosamine hydrochloride

A relatively simple, selective, precise and accurate high performance liquid chromatography (HPLC) method based on a reaction of phenylisothiocyanate (PITC) with glucosamine (GL) in alkaline media was developed and validated to determine glucosamine hydrochloride permeating through human skin in vitro. It is usually problematic to develop an accurate assay for chemicals traversing skin because the excellent barrier properties of the tissue ensure that only low amounts of the material pass through the membrane and skin components may leach out of the tissue to interfere with the analysis. In addition, in the case of glucosamine hydrochloride, chemical instability adds further complexity to assay development. The assay, utilising the PITC-GL reaction was refined by optimizing the reaction temperature, reaction time and PITC concentration. The reaction produces a phenylthiocarbamyl-glucosamine (PTC-GL) adduct which was separated on a reverse-phase (RP) column packed with 5 microm ODS (C18) Hypersil particles using a diode array detector (DAD) at 245 nm. The mobile phase was methanol-water-glacial acetic acid (10:89.96:0.04 v/v/v, pH 3.5) delivered to the column at 1 ml min-1 and the column temperature was maintained at 30 degrees C. Galactosamine hydrochloride (Gal-HCl) was used as an internal standard. Using a saturated aqueous solution of glucosamine hydrochloride, in vitro permeation studies were performed at 32+/-1 degrees C over 48 h using human epidermal membranes prepared by a heat separation method and mounted in Franz-type diffusion cells with a diffusional area 2.15+/-0.1 cm2. The optimum derivatisation reaction conditions for reaction temperature, reaction time and PITC concentration were found to be 80 degrees C, 30 min and 1% v/v, respectively. PTC-Gal and GL adducts eluted at 8.9 and 9.7 min, respectively. The detector response was found to be linear in the concentration range 0-1000 microg ml-1. The assay was robust with intra- and inter-day precisions (described as a percentage of relative standard deviation, %R.S.D.) <12. Intra- and inter-day accuracy (as a percentage of the relative error, %RE) was <or=-5.60 and <or=-8.00, respectively. Using this assay, it was found that GL-HCl permeates through human skin with a flux 1.497+/-0.42 microg cm-2 h-1, a permeability coefficient of 5.66+/-1.6x10(-6) cm h-1 and with a lag time of 10.9+/-4.6 h.

β-Arrestin2 influences the response to methadone in opioid-dependent patients.

β-Arrestin2 (ARRB2) is a component of the G-protein-coupled receptor complex and is involved in μ-opioid and dopamine D(2) receptor signaling, two central processes in methadone signal transduction. We analyzed 238 patients in methadone maintenance treatment (MMT) and identified a haplotype block (rs34230287, rs3786047, rs1045280 and rs2036657) spanning almost the entire ARRB2 locus. Although none of these single nucleotide polymorphisms (SNPs) leads to a change in amino-acid sequence, we found that for all the SNPs analyzed, with exception of rs34230287, homozygosity for the variant allele confers a nonresponding phenotype (n=73; rs1045280C and rs2036657G: OR=3.1, 95% CI=1.5-6.3, P=0.004; rs3786047A: OR=2.5, 95% CI=1.2-5.1, P=0.02) also illustrated by a 12-fold shorter period of negative urine screening (P=0.01). The ARRB2 genotype may thus contribute to the interindividual variability in the response to MMT and help to predict response to treatment.

Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with l- and d,l-methadone.

Sixty d,l- or l-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P=0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower d,l- (P<0.05) and l-methadone dose than non-comorbid subjects. The duration of maintenance treatment showed an inverse relationship to frequency of additional heroin intake (P<0.01). Patients with additional heroin intake over the past 30 days had been treated with a significantly lower l-methadone dosage (P<0.05) than patients without. Axis-I comorbidity appears to be decreased when relatively higher dosages of d,l- (and l-methadone) are administered; comorbid individuals, however, were on significantly lower dosages. Finally, l-, but not d,l-methadone seems to be more effective in reducing additional heroin abuse.

Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

Synthesis, characterization and kinetic studies on complex formed between amantadine hydrochloride and sodium molybdate at physiological pH

The title reaction was undertaken to establish the interaction between amantadine and molybdate at physiological pH. Identical FTIR spectra, TG-DTA curves and CHN data of the complexes formed from three solutions at pH 1.5, 7.4 and 8.0 indicate that the same complex was formed at all the three pHs. The FTIR spectrum shows shift in peaks corresponding to primary amino group of the drug due to coordination to molybdate. An octahedral geometry is assigned to the complex. The kinetics of the complexation has been studied at low concentrations of the reactants using UV-visible spectrophotometry. At pH 7.4, the initial rate varies linearly with [molybdate]. A plot of initial rate versus [drug] is linear passing through origin. These results indicate that the drug and molybdate react at pH 7.4 even at low concentrations. At pH 1.5, the rate increases linearly with increase in [drug] but decreases with [molybdate]. The effect of pH and ionic strength on the rate of the reaction has also been studied. A suitable mechanism has been proposed for the reaction. Reaction between the drug and molybdate even at low concentrations and the fact that the amino group of amantadine required to be free for its function as antiviral, is bound to molybdate in the complex suggests that simultaneous administration of the drug and molybdate supplements should be avoided.

Electrochemical studies of tamsulosin hydrochloride using multiwalled carbon nanotube-modified glassy carbon sensor

A differential pulse voltammetric sensor for the determination of tamsulosin hydrochloride (TAM) using multiwalled carbon nanotubes (MWNTs)–Nafion-modified glassy carbon electrode (GCE) has been developed. MWNTs were dispersed in water with the help of Nafion and were used to modify the surface of GCE via solvent evaporation. At MWNT-modified electrode, TAM gave a well-defined oxidation peak at a potential of 1084 mV in 0.1 M acetate buffer solution of pH 5. Compared to the bare electrode, the peak current of TAM showed a marked increase and the peak potential showed a negative deviation. The determination conditions, such as the amount of MWNT–Nafion suspension, pH of the supporting electrolyte and scan rate, were optimised. Under optimum conditions, the oxidation peak current was proportional to the concentration of TAM in the range 1 × 1023 M–3 × 1027 M with a detection limit of 9.8 × 1028 M. The developed sensor showed good stability, selectivity and was successfully used for the determination of TAM in pharmaceutical formulations and urine samples

An optimized reverse-phase high performance liquid chromatographic method for evaluating percutaneous absorption of glucosamine hydrochloride

A relatively simple, selective, precise and accurate high performance liquid chromatography (HPLC) method based on a reaction of phenylisothiocyanate (PITC) with glucosamine (GL) in alkaline media was developed and validated to determine glucosamine hydrochloride permeating through human skin in vitro. It is usually problematic to develop an accurate assay for chemicals traversing skin because the excellent barrier properties of the tissue ensure that only low amounts of the material pass through the membrane and skin components may leach out of the tissue to interfere with the analysis. In addition, in the case of glucosamine hydrochloride, chemical instability adds further complexity to assay development. The assay, utilising the PITC-GL reaction was refined by optimizing the reaction temperature, reaction time and PITC concentration. The reaction produces a phenylthiocarbarnyl-glucosamine (PTC-GL) adduct which was separated on a reverse-phase (RP) column packed with 5 mu m ODS (C-18) Hypersil particles using a diode array detector (DAD) at 245 nm. The mobile phase was methanol-water-glacial acetic acid (10:89.96:0.04 v/v/v, pH 3.5) delivered to the column at 1 ml min(-1) and the column temperature was maintained at 30 degrees C Using a saturated aqueous solution of glucosamine hydrochloride, in vitro permeation studies were performed at 32 +/- 1 degrees C over 48 h using human epidermal membranes prepared by a heat separation method and mounted in Franz-type diffusion cells with a diffusional area 2.15 +/- 0.1 cm(2). The optimum derivatisation reaction conditions for reaction temperature, reaction time and PITC concentration were found to be 80 degrees C, 30 min and 1 % v/v, respectively. PTC-Gal and GL adducts eluted at 8.9 and 9.7 min, respectively. The detector response was found to be linear in the concentration range 0-1000 mu g ml(-1). The assay was robust with intra- and inter-day precisions (described as a percentage of relative standard deviation, %R.S.D.) < 12. Intra- and inter-day accuracy (as a percentage of the relative error, %RE) was <=-5.60 and <=-8.00, respectively. Using this assay, it was found that GL-HCI permeates through human skin with a flux 1.497 +/- 0.42 mu g cm(-2) h(-1), a permeability coefficient of 5.66 +/- 1.6 x 10(-6) cm h(-1) and with a lag time of 10.9 +/- 4.6 h. (c) 2005 Elsevier B.V. All rights reserved.

What GPs need to know about palliative-care drugs : methadone

This is the second in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist‐initiated palliative‐care drugs. Here, the authors summarise the key issues around the use of methadone for pain management.