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Morphine suppresses respiration for longer periods of time when it is injected into the spinal column than when it is given intravenously. This indicates that morphine and other opioids can directly affect the central nervous system.

Acetaminophen overdose is a leading cause of drug-induced liver failure in the United States. Acetaminophen-protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein-derived acetaminophen-protein adducts are quantifiable in postmortem samples. Heart blood, femoral blood, and liver tissue were collected at autopsy from 22 decedents suspected of opioid-acetaminophen overdose. Samples were assayed for protein-derived acetaminophen-protein adducts, acetaminophen, and selected opioids found in combination products containing acetaminophen. Protein-derived APAP- CYS was detected in 17 of 22 decedents and was measurable in blood that was not degraded or hemolyzed. Heart blood concentrations ranged from 11 ng/ mL (0.1 μM) to 7817 ng/ mL (28.9 μM). Protein-derived acetaminophen-protein adducts were detectable in liver tissue for 20 of 22 decedents. Liver histology was also performed for all decedents, and no evidence of centrilobular hepatic necrosis was observed. [ABSTRACT FROM AUTHOR]

1. It has been suggested that acetaminophen (APAP)-protein adducts can be measured in circulation to diagnose APAP-induced liver injury. However, the full-time course of plasma adducts has not been studied specifically in early-presenting overdose patients. In fact, surprisingly little work has been done on the metabolism of APAP after overdose in general. 2. We measured APAP, five APAP metabolites and APAP-protein adducts in plasma samples from early- and late-presenting overdose patients, and APAP-protein adducts in culture medium from HepaRG cells. 3. In contrast to earlier rodents studies, we found that APAP-protein adducts were lower at early time points and peaked around the time of peak liver injury, suggesting that these adduct levels may take longer to become elevated or remain elevated than previously thought. 4. APAP and its major metabolites were elevated in plasma at early time points and rapidly decreased. 5. Although clinical measurement of APAP-protein adducts holds promise as a diagnostic tool, we suggest caution in its interpretation in very early-presenting patients. Our data also support the idea that sulfation is saturated even at low doses but glucuronidation has a much higher capacity, highlighting the importance of glucuronidation in APAP metabolism. [ABSTRACT FROM AUTHOR]

The article discusses the action of human androgen receptor (hAR) and its relevance to sport doping, and its use in biological assays. It explores the transcriptional activation of hAR to determine the presence of its biological activity agonists and antagonists when used as competitive assays. It notes that hAR biological assay is the next generation of detection method in antidoping field.

Grapefruit juice ingested concurrently with several classes of drugs can profoundly influence drug effects and toxicity. Fatal interactions have been reported. Grapefruit juice inhibits cytochrome P450 3A (CYP3A) enzymes and may inhibit cytochrome P450 1A2 (CYP1A2) enzymes.2,5 This can inhibit metabolism of drugs whose metabolic fate relies upon those enzymes. Only orally administered drugs are effected. First-pass metabolism mediated by the CYP3A subfamily of enzymes is a common property shared by drugs that interact with grapefruit juice.2 Also, drugs that undergo a significant first-pass metabolism with a lower bioavailability ranging from 5% to 30% may be affected to a greater degree by grapefruit juice.2 Drugs that interact with grapefruit juice include antiepileptic agents, antimicrobial agents, benzodiazepines, calcium channel blockers, HMG-CoA reductase inhibitors, hormones, immunosuppressant agents, and others. Reported interactions are summarized. [ABSTRACT FROM PUBLISHER]

Presents cases of benzonatate poisoning with seizures and cardiac arrest. Recommended dose of benzonatate antitussive agent; Details of the use of high-pressure liquid chromatography in quantifying benzonatate; Danger associated with benzonatate overdose.

The effects on the upper gastrointestinal tract of five different preparations of KCl were compared in 90 healthy subjects treated with glycopyrrolate. The KCl preparations studied were (1) wax-matrix KCI, (2) microencapsulated KCI, (3) liquid KCI, (4) experimental extended-release capsules, (5) experimental extended-release tablets, and (6) placebo. The subjects were endoscoped prior to and after seven days of dosing. Upper gastrointestinal mucosal pathology was seen with all of the potassium preparations as well as with placebo. No statistically significant differences between the various KCI groups or between KCI groups and placebo were seen. All of the lesions were superficial, except for one ulcer seen with the microencapsulated KCI. None of the subjects developed occult gastrointestinal bleeding. There were no differences in the incidence of abdominal symptoms. [ABSTRACT FROM AUTHOR]

Antibiotic-induced pseudomembraneous colitis has been described following therapy with lincomycin, clindamycin, ampicillin, tetracycline and chloramphenicol. Despite the association of arthritis with inflammatory intestinal disease, to our knowledge there are no reports in the literature of arthritis occurring with antibiotic-induced colitis. We will report a case of pseudomembraneous colitis with acute migratory polyarthritis following therapy with clindamycin. [ABSTRACT FROM AUTHOR]

Presents a study that examined the interaction between quinidine and digoxin. Pharmacokinetic values of digitoxin disposition with and without quinidine; Effect of quinidine on the distribution and elimination of digoxin; Characteristics of digitoxin.

Renin-aldosterone profiling was used to classify patients with hypertension: 243 patients with essential hypertension were classified by renin-urinary sodium indexing; 107 were reclassified by response to administration of furosemide and intravenous saline; 45 were further classified by response to a low-sodium diet. Arbitrary "normal ranges" were determined in 89, 32, and 38 volunteers, respectively. Patients with low-renin apparently do not have "high-volume" hypertension. Rather, they show a primary renal abnormality in renin secretion and become relatively deficient in angiotensin II and aldosterone when they are subjected to diuresis. They can maintain aldosterone secretion under normal conditions because their adrenal aldosterone receptor is supersensitive to angiotensin II. No evidence of abnormal sympathetic neural activity was found among the renin subgroups. Renin-aldosterone profiling in current clinical practice seems useful mainly in the detection of patients with curable forms of secondary hypertension. Aldosterone/renin ratios may be particularly helpful in diagnosis when obtained after a patient has undergone expansion or contraction of his extracellular fluid volume. [ABSTRACT FROM AUTHOR]

The article reports on the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to detect nicotine biomarkers in hair and evaluation of wash procedures for environmental nicotine removal. It notes the application of this procedure to heavy smoker hair samples and to low weight low-level smoker hair samples. Study shows that the presence of quantifiable anatabine (AT), and nornicotine (NNIC) concentrations may determine heavy and low-level smokers.

The article presents a study which attempts to both identify and quantify potential nicotine (NIC) biomarkers from individuals receiving low-dose transdermal nicotine. It states that the study uses oral fluid samples collected by liquid chromatography-tandem mass spectrometry with analytes extracted by solid phase extraction and further tests by enzyme-linked immunosorbent assay (ELISA). It reveals that the alkaloids from the oral fluid has been successfully developed and validated.

Investigates whether hair can be used as an adjunct specimen for monitoring opiate use in a drug-treatment program. Analysis of codeine, morphine and 6-monoacetylmorphine use; Analysis of segmental hair data; Sensitivity of urine data for monitoring drug use.

A large subset of individuals who smoke cigarettes do not smoke regularly, but the assessments used to collect data on cigarette consumption in nondaily smokers have not been rigorously evaluated. The current study examined several self-report and biomarker approaches to the assessment of cigarette use in a sample of nondaily smokers (n = 176). Participants were randomly assigned to a daily monitoring condition (n = 89), requiring a daily report of the number of cigarettes smoked in the previous 24 hours, or a no monitoring condition (n = 87). Number of cigarettes smoked over the first 28 days of the study was assessed using 2 quantity frequency measures, a graduated frequency measure, and a timeline follow back (TLFB) interview at the Session 5 study visit. Hair nicotine (NIC), hair cotinine (COT), and expired-air carbon monoxide (CO) were collected from each participant. Total cigarettes reported via daily report were strongly correlated with all Session 5 measures of total cigarettes, but were most strongly associated with TLFB total cigarettes. Collapsed CO across 5 sessions was the biomarker most strongly correlated with daily report total cigarettes. The results support the use of daily report and TLFB methods of assessing cigarette use in nondaily smokers. Results also support the use of CO as appropriate biological markers of exposure in nondaily smokers, and point to some limitations in the use of hair biomarkers in this population. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

Focuses on the use of antibiotic ofloxacin as a reference marker in hair of various colors and evaluates the efficacy of a reliable marker substance to human subjects in identifying drug use and treatment compliance in drug treatment programs. Benefits of hair analysis in monitoring compliance and recidivism in drug treatment programs; Overview of analytical procedures used in this evaluation; Account of ofloxacin and eumelanin in human hair of various colors.

Presents a study that focuses on the in vitro binding of cocaine, benzoylecgonine, amphetamine and N-acetylamphetamine to synthetic melanin subtypes to assess the role of individual melanin subtypes in binding these materials. Overview of binding experiments and analysis used in this study; Account of melanin used in this study; Use of hyperbolic binding data plot for cocaine binding to dihydroxyindole-melanin; Evidence for the amphetamine-oxidized catechol dimer adduct.

Determines the use of hair and urine as adjunct specimens for the monitoring of opiate use in a drug treatment program. Overview of subjects initiating clinical therapy for opiate addiction; Account of opiate recidivism in this treatment program; Information about potential effects of hair color and chemical treatment on quantitative hair data.