The assessment and management of gamma hydroxybutyrate use in general practice.

BACKGROUND: Gamma hydroxybutyrate (GHB) is an illicit drug commonly used in music festival, party and 'chemsex' settings. Most people who use GHB do so occasionally, without dependent use or withdrawal symptoms. However, a minority of users experience harms including unconsciousness and respiratory collapse in overdose. Adverse interactions can also occur when GHB is used with other drugs (eg methamphetamine), necessitating assessment, management or onward referral by general practitioners. OBJECTIVE: This article describes the use of GHB, with a contemporary update on principles of assessment and management in general practice, brief intervention and harm-minimisation strategies, and indicators for referral to a specialist in dependent use. DISCUSSION: The assessment and management of individuals with GHB-related harms in general practice is supported by an awareness of the context of use, familiarity with targeted harm-minimisation advice and cognisance of markers of risk indicating onward referral to specialist addiction services when appropriate.

Detection and identification of medically important alkaloids using the surface-enhanced Raman scattering spectroscopy.

Currently, trace detection of drugs, medicinal products, psychoactive substances, poisons and other natural or synthetic compounds in the human body has become one of the most important areas of interest in medicine, toxicology and forensic research. Due to the rapid development of nanotechnology, applications in forensic and biological sciences, food industry and art preservation there is an increasing interest in surface-enhanced Raman scattering (SERS) spectroscopy as a technique capable of low detection limits in the analysis of small amounts of studied analytes. In this study, different excitation wavelengths (785 nm and 1064 nm) were used to find the appropriate experimental conditions for the detection and identification of medically significant alkaloids - atropine and pergolide - by means of surface-enhanced Raman scattering spectroscopy. SERS spectra of selected alkaloids were measured in the concentration range 10-3-10-9 mol∙L-1 using large-scaled platinum substrates coated with electrochemically prepared gold or silver SERS-active layers. Identification was based on the assignment of surface-enhanced characteristic vibrational bands using theoretical (DFT) calculations and comparing them with normal (non-enhanced) Raman spectra of pure compounds. All sets of spectral data were subjected to multivariate statistical approach (partial least squares regression) aiming at prediction of alkaloids concentration in developed models and its comparison with experimental results.

Estudo clínico e histológico das pálpebras e conjuntiva hígidas submetidas ao tratamento tópico com soluções anestésicas em coelhos / Clinical and histological evaluation of healthy eyelid and conjunctiva subject to local treatment with anesthetic solutions in rabbits

Avaliaram-se as apresentações comerciais de colírios anestésicos aplicados em 63 coelhos da raça Nova Zelândia, distribuídos em três grupos (G1, G2 e G3) de 21 animais cada e que receberam instilação de uma gota em cada olho seis vezes ao dia. Os animais do G1 foram tratados com colírio de cloridrato de proparacaína a 0,5%; os do G2, com colírio de cloridrato de tetracaína a 1% associado à fenilefrina a 0,1%; e os do G3, com solução fisiológica. Cada grupo foi subdividido em três subgrupos com sete animais cada, os quais foram tratados por três, sete e 15 dias. No final de cada tratamento, dois animais de cada subgrupo foram sacrificados para exame histológico de fragmentos retirados da conjuntiva, da terceira pálpebra e das pálpebras. Observou-se, ao exame clínico, episclerite em graus diversos em 100% dos animais do G1, no terceiro, sétimo e 15º dia, e em apenas 17,8% nos do G2, nestes mesmos dias. Ao exame microscópico, observaram-se aumento do número de células califormes, proliferação de folículos linfoides, aumento do número de eosinófilos e aumento do espaço intersticial nas pálpebras dos animais do G1. Pôde-se concluir que o colírio de tetracaína a 1% associado à fenilefrina a 0,1% promoveu maior toxicidade à conjuntiva ocular e às pálpebras de coelhos quando comparado ao colírio de proparacaína a 0,5%.

This work aimed to evaluate commercial presentations of anesthetic eye drops in sixty three New Zealand rabbits which were separated equally in three groups (G1, G2 and G3). The G1 group was treated with 0.5% proparacaine chloridrate eye drop, G2 group with 1% tetracaine chloridrate associated with 0.1% phenylephrine eye drop and G3 group with 0.9% physiologic solution eye drop. All of them received one drop in each eye six times a day. Each group was subdivided into three subgroups (seven rabbits), which are treated for 3, 7 and 15 days. At the end of each treatment, two animals in each subgroup were subject to euthanasia, for the purpose of conjunctiva, eyelids and third eyelids histological evaluation. At the clinical exam, different grades of episcleritis were found in all rabbits in G2 group and only in 17.8% of the rabbits in G1 group. Eye and eyelid histologic evaluation of G2 group revealed an upgrade of goblet cells and eosinophil number, lymphoid follicle proliferation and increase of interstitial space in the eyelids. We could conclude that 1% tetracaine associated with 0.1% phenylephrine eye drop caused more eyelid and ocular conjunctiva toxicity than 0.5% proparacaine eye drop.

Simultaneous determination of ropivacaine, bupivacaine and dexamethasone in biodegradable PLGA microspheres by high performance liquid chromatography.

A simple and rapid high-performance liquid chromatography method coupled with UV detector was developed and validated for the simultaneous determination of ropivacaine, bupivacaine and dexamethasone in biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres within 11 min. Chromatographic separation was performed on a XDB-C(18) column using a mobile phase comprised of acetonitrile-NaH(2)PO(4) buffer (pH 3.5, 30 mM) (30:70, v/v) with a flow rate gradient program. The method was in good linearity (r>0.999) over the range of 0.025-40.0 microg/ml for ropivacaine and bupivacaine, and 0.05-40 microg/ml for dexamethasone. The method was proved to be precise with intra- and inter-day precision less than 3.0% and 6.0% for all drugs and accurate with intra- and inter-day accuracy between -8.0% to 4.5% and between -5.0% to 5.5% for all drugs. The assay was rapid, simple and easy to apply. Therefore, it was very suitable for routine determination and quality control of ropivacaine, bupivacaine and dexamethasone in PLGA microspheres.

A comparison of epinephrine concentrations in local anesthetic solutions using a "wash" versus measured technique.

INTRODUCTION: Anesthesiologists often prepare epinephrine-containing local anesthetic solutions. We compared epinephrine concentrations of solutions prepared using the "wash" technique with solutions prepared using the measured technique (using an insulin syringe), and compared epinephrine concentrations among anesthesiologists. METHODS: Five anesthesiologists prepared syringes for spinal and epidural anesthesia using both techniques. Epinephrine concentrations were measured using high-performance liquid chromatography. RESULTS: Measured technique concentrations were higher than those of the wash technique for the spinal but not epidural solutions. CONCLUSIONS: Concentrations of all measured spinal solutions were higher than the target concentrations, as were concentrations of three of five measured epidural solutions. There were significant differences among anesthesiologists.

Potential surrogate markers for gamma-hydroxybutyrate administration may extend the detection window from 12 to 48 hours.

The exogenous administration of gamma-hydroxybutyrate (GHB) as a drug of abuse, and especially in date rape sexual assaults, has recently increased. Chromatographic techniques are used to detect GHB in blood or urine, with a window of detection limited to 12 h. This brief window makes the proof of administration problematic in most rape cases. This study is aimed to extend the window of detection through surrogate markers of GHB administration. Microarray technology is used in a DBA/2J mouse model to detect gene expression changes in peripheral blood after GHB exposure at times as long as 96 h post exposure. This study focuses on two of the most significantly altered transcripts, epiregulin and phosphoprotein enriched in astrocytes 15 (Pea-15). Both genes have increased the ribonucleic acid expression (8.5- and 4.6-fold upregulation at 96 h, respectively) in GHB-dosed mice (1 g/kg) as compared with the control. To confirm these results at the protein level, an intracellular flow cytometric assay is developed to detect protein level changes in the peripheral blood of both these potential biomarkers after GHB exposure. These results suggest that after further development, epiregulin and Pea-15 may prove to be significant surrogate markers in the indirect detection of GHB administration.

Detection of gamma-hydroxybutyrate in striatal microdialysates following peripheral 1,4-butanediol administration in rats.

The illicit use and abuse of 1,4-butanediol (1,4-BD) results from its presumed conversion to gamma-hydroxybutyrate (GHB) and subsequent pharmacological effects via action on GABA-B and GHB-specific receptors. Using in vivo microdialysis we measured the appearance of GHB in the striata of rats after peripheral 1,4-BD administration. We developed and utilized an HPLC-UV (215 nm) detection of GHB that yielded a limit of quantification (S/N=10) of 2.0 micro g/mL (40 ng/injection) and a limit of detection (S/N=3) of 0.75 micro g/mL (15 ng/injection). GHB appeared in the striatal microdialysates within 20 min after intraperitoneal (i.p.) administration of varying doses of 1,4-BD. GHB concentrations reached dose-dependent maxima 80-100 min post-1,4-BD administration, with peak values of 10.6+/-2.9, 25.3+/-3.4 and 48.1+/-7.1 micro g/mL (mean+/-S.E.M.), corresponding to 1,4-BD doses of 250, 500 and 750 mg/kg, respectively. The conversion of 1,4-BD to GHB was completely prevented by the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP), administered prior to 1,4-BD, as evidenced by the failure of GHB to appear in the striatal microdialysates. Sleep times in animals were similarly correlated with GHB concentrations in the microdialysates.

Variations in the composition of spinal anesthetic solutions: the effects of drug addition order and preparation methods.

UNLABELLED: Adjuvants such as opioids or epinephrine are commonly added in small volumes to multicomponent spinal anesthetic solutions. In this study, we tested the hypothesis that final adjuvant concentrations vary depending on the devices and techniques used to prepare the anesthetic solution. We compared two aspiration devices, the filter needle and the filter straw, in a laboratory study. Two techniques for drawing up and estimating adjuvant volumes were assessed, as was variation in the composition of a model spinal anesthetic solution resulting from intra- and interindividual variability. A model hyperbaric anesthetic solution consisting of tetracaine, dextrose, and methylene blue (MB) as a small-volume tracer solution was studied. The components were drawn up into a syringe through one of two commercially supplied aspiration devices, a filter straw or a filter needle. The effect of the order of aspiration of the components into the syringe was measured by determining the MB concentration in the final solution by optical absorbance. Ten experienced anesthesiologists then prepared samples of the test solution using one of two different techniques to estimate tracer volume in the aspiration syringe. In comparison studies, the MB tracer was added to the hyperbaric solution with a tuberculin syringe. The order of aspiration of the solution components had a large effect on the final concentration of the MB tracer in the ultimate mixture. Variation in the MB concentration was on the order of four- to fivefold. Effects were larger for the filter straw compared with the filter needle. A comparison of 10 anesthesiologists revealed large intra- and interindividual variations in the final composition of the model anesthetic solution. The concentration of tracer added to the mixture with a tuberculin syringe approximated the planned yield. We conclude that the devices and techniques used to prepare mixtures of drugs for delivery to the cerebrospinal fluid may influence the concentrations of drugs in the anesthetic and, thus, the dose supplied to the patient receiving spinal anesthesia. Variation in clinical effects of spinal anesthetics may be attributable, in part, to variation in the composition of the anesthetic. IMPLICATIONS: This laboratory study demonstrates the potential for large variation in the composition of spinal anesthetic mixtures.

Compatibility and stability of fentanyl admixtures in polypropylene syringes.

OBJECTIVE: To determine the physicochemical stability of fentanyl in combination with midazolam and either hyoscine butylbromide or metoclopramide, and stored in 30 ml polypropylene syringes. METHODS: Solutions containing approximately 40 microg/ ml of fentanyl in combination with midazolam (approximately 600 microg/ml) and either metoclopramide (approximately 700 microg/l) or hyoscine (approximately 850 microg/ml) were prepared from commercial ampoules of the drugs. The solutions were stored, in triplicate, in the dark at 32 degrees C (to simulate usage conditions) for 10 days, and the concentration of each constituent drug was periodically determined using a stability-indicating high-performance liquid chromatography assay. RESULTS: The combinations were relatively stable, with all drugs maintaining over 90% of their initial chemical potency for at least 1 week. There were no evident changes in either the physical appearance or pH values of the solutions over the course of the study. CONCLUSIONS: On the basis of physicochemical stability, polypropylene syringes containing fentanyl with midazolam and either hyoscine butylbromide or metoclopramide can be safely prepared and stored at or below 32 degrees C for periods of up to 1 week prior to use by palliative care patients receiving the drugs via a portable subcutaneous infusion device.