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Drug Interactions (drug + interaction)
Kinds of Drug Interactions Terms modified by Drug Interactions Selected AbstractsEffect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food,Drug InteractionJOURNAL OF FOOD SCIENCE, Issue 3 2010Ming-Ji Jin ABSTRACT:, The present study aimed to investigate the effect of piperine, a major component of black pepper, on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) or intravenous (5 mg/kg) administration of fexofenadine in the presence and absence of piperine (10 or 20 mg/kg, given orally). Compared to the control group given fexofenadine alone, the combined use of piperine increased the oral exposure (AUC) of fexofenadine by 180% to 190% while there was no significant change in,Cmax and,T1/2 of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore,,Tmax tends to be increased which might be attributed to the delayed gastric emptying in the presence of piperine. In contrast, piperine did not alter the intravenous pharmacokinetics of fexofenadine, implying that piperine may increase mainly the gastrointestinal absorption of fexofenadine rather than reducing hepatic extraction. In conclusion, piperine significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal absorption, suggesting that the combined use of piperine or piperine-containing diet with fexofenadine may require close monitoring for potential drug,diet interactions. [source] Bench to Bedside: Pharmacogenomics, Adverse Drug Interactions, and the Cytochrome P450 SystemACADEMIC EMERGENCY MEDICINE, Issue 12 2005Rishi Sikka MD As physicians attempt to improve the quality of health care, one area of particular concern has been preventable medical errors from adverse drug interactions. The cytochrome P450 family of enzymes has been implicated in a large number of these preventable, adverse drug interactions. This report reviews the basic biochemistry and pharmacogenomics underlying the reactions catalyzed by the cytochrome P450 family of enzymes. An emphasis is placed on the phenotypic variations within a population and the resulting clinical effects. In addition, six members of the cytochrome P450 superfamily that are responsible for the metabolism of the majority of pharmaceutical agents are profiled in detail. These enzymes, CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2, are reviewed with regard to their phenotypic variation in the population and the resulting clinical and therapeutic implications. [source] Handbook of Drug Interactions: A Clinical and Forensic GuideEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2004K. A. Jellinger No abstract is available for this article. [source] Potential for Alcohol and Prescription Drug Interactions in Older PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2005Kristine E. Pringle PhD Objectives: To examine the patterns and prevalence of concomitant alcohol and alcohol-interactive (AI) drug use in older people. Design: Cross-sectional analysis of survey and prescription claims data. Setting: The Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PA-PACE) program, a state-funded program providing prescription benefits to older people with low to moderate incomes. Participants: A total of 83,321 PA-PACE cardholders (age range 65,106) who were using any prescription medications at the time of survey completion. Measurements: All AI drugs were identified using a database of medication warning labels obtained from First DataBank. Prescription drug claims were used to characterize AI drug exposure according to therapeutic class of prescription drug use. A mail survey of PA-PACE cardholders was used to examine alcohol use, as well as sociodemographic and health factors associated with concomitant use of alcohol and AI drugs. Results: Seventy-seven percent of all prescription drug users were exposed to AI medications, with significant variation in exposure and concomitant alcohol use according to therapeutic class. Overall, 19% of AI drug users reported concomitant alcohol use, compared with 26% of non-AI drug users (P<.001). Multinomial logistic regression analyses showed that certain groups of older people, including younger older people, men, and those with higher educational levels, were at greater risk for concomitant exposure to alcohol and AI drugs. Conclusion: Many older people use alcohol in combination with AI prescription drugs. Clinicians should warn every patient who is prescribed an AI drug about alcohol,drug interactions, especially those at high risk for concomitant exposure. [source] Drug Interactions of Clinical Importance with Methadone and BuprenorphineTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Elinore F. McCance-Katz MD [source] Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and Other Frequently Prescribed Medications: A ReviewTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Elinore F. McCance-Katz MD Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.,(Am J Addict 2009;19:4,16) [source] Drug Interactions between Antiretroviral Medications and Medications Used in the Treatment of Drug Addiction: Research NeedsTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Jag H. Khalsa PhD Today substance dependence is one of the major public health problems in the world with millions of people abusing legal and illegal drugs. In addition, almost one-third of the world's population suffers with one or more infections. Both drugs of abuse and infections are associated with serious medical and health consequences, some of which may be exacerbated by the occurrence of pharmacokinetic and/or pharmacodynamic interactions between medications used in the treatment of these conditions when they co-occur. This review briefly discusses issues surrounding clinical management related to drug interactions experienced by substance abusing patients. The emphasis of this paper is on the research needed to further study the extent, nature, and underlying molecular/genetic mechanism(s) of interactions between drugs of abuse, medications used in the treatment of drug addiction, and co-occurring infections.,(Am J Addict 2009;19:96,100) [source] Physiologically Based Modelling and Prediction of Drug InteractionsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2010Frédéric Y. Bois This article reviews briefly past developments in the area of physiologically based pharmacokinetic (PBPK) modelling of interactions. It also demonstrates a systems biology approach to the question, and the capabilities of new software tools to facilitate that development. Individual Systems Biology Markup Language models of metabolic pathways can now be automatically merged and coupled to a template PBPK pharmacokinetic model, using for example the GNU MCSim software. The global model generated is very efficient and able to simulate the interactions between a theoretically unlimited number of substances. Development time and the number of model parameter increase only linearly with the number of substances considered, even though the number of possible interactions increases exponentially. [source] Cancer Patients at Risk of Drug InteractionsCA: A CANCER JOURNAL FOR CLINICIANS, Issue 5 2007Article first published online: 31 DEC 200 No abstract is available for this article. [source] A Comparison of the Effects of Olopatadine and Ketotifen on Model MembranesACTA OPHTHALMOLOGICA, Issue 2000Howard Brockman ABSTRACT. Olopatadine is a human conjunctival mast cell stabilizer with anti-histaminic activity. Ketotifen is an older molecule that possesses antihistaminic activity and is reported to have additional pharmacological properties. The interactions of these two compounds with model membranes (i.e., monolayers of 1-stearoyl-2-oleoyl-sn-glycerophosphocholine at the argon-buffer interface), and natural (i.e., erythrocyte) membranes were compared in an effort to understand the differences in their biological activities. Drug-lipid interaction with monolayers was determined by monitoring the surface pressure as a function of the drug concentration in the aqueous phase supporting the monolayer. Drug interaction with erythrocyte membranes was determined by monitoring changes in the permeability of the membranes to hemoglobin and 6-carboxyfluorescein as a function of drug concentration in the medium. Olopatadine and ketotifen are both intrinsically surface active and both interact with phospholipid monolayers. However, in both the presence and absence of lipid monolayers, the changes in surface pressure induced by olopatadine are lower than those caused by ketotifen. The effects of these two drugs on cell membranes were dramatically different. Exposure of bovine erythrocytes to increasing concentrations of ketotifen (1,10 mM) resulted in complete hemolysis of the cells, whereas olopatadine (1,10 mM) caused only minimal hemolysis (<8%). Consistent results were obtained in experiments measuring the leakage of 6-carboxyfluorescein from erythrocyte ghosts as a more sensitive marker of membrane perturbation. Olopatadine treatment (0.1,10 mM) minimally perturbed the cell membrane while ketotifen (1,10 mM) caused a concentration dependent release of the fluorescent marker. These data demonstrate fundamental differences between the two drugs in their effects on cell membranes. Moreover, the differences are consistent with the surface activities of the two compounds measured in monolayers and with reported differences in their pharmacological activities. These findings offer an explanation for the biphasic non-specific cytotoxic effect of ketotifen on histamine release from mast cells and may account for the non-lytic mast cell stabilizing activity of olopatadine. [source] Drug interactions: a review and updateENDODONTIC TOPICS, Issue 1 2003B. Ellen Byrne First page of article [source] Current therapy of HIVJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2010Anja Verena Potthoff Summary Antiretroviral therapy has improved continuously. Almost every year a new drug has been approved. Nucleoside analogs still build the backbone of antiretroviral therapy. They inhibit reverse transcriptase and thus the transcription of RNA to DNA. They are combined with non-nucleoside reverse transcriptase inhibitors or protease inhibitors. New therapeutic approaches are attachment or entry inhibitors, integrase inhibitors and maturation inhibitors. Multiple prospective multicenter studies have proven the life prolonging effect of antiretroviral therapy. With the optimal therapy life expectancy of HIV patients is only slightly reduced, similar to that of those with chronic diseases such as diabetes mellitus. One result of the higher age of HIV patients is an increase in concomitant diseases and medications. Drug interactions have to be considered and avoided. There has been a long discussion about the best time point to start antiretroviral therapy. In the late 1990s, every infected patient was treated hoping to eliminate the virus, ignoring the CD4+ cell count and viral load. This caused multiple (long-term) side effects and a rising resistance problem. The guidelines now recommend starting therapy at about 350/,l CD4 lymphocytes. Due to its complexity antiretroviral therapy should be initiated and monitored in specialized centers. [source] Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatmentJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2000U-F. Haustein Abstract Objective,To evaluate the efficacy, safety and side-effects of methotrexate (MTX) in psoriasis. Design,A 26-year retrospective study. Setting,Department of Dermatology, Leipzig University, Leipzig, Germany. Patients,One hundred and fifty-seven patients with extensive plaque psoriasis, erythrodermic, pustular and arthropathic forms, were treated with low-dose methotrexate (15,20 mg maximum weekly dosage [Weinstein schedule]), the majority for long-term periods. The mean cumulative dose was 3394 mg, the mean duration 237 weeks. Results,The effect of MTX treatment was good in 76%, moderate in 18% and poor in 6% of subjects; 61% experienced side-effects, most frequently due to liver function abnormalities, bone marrow suppression, nausea, gastric complaints and hair loss. In 20% of cases the subjects were forced to discontinue therapy; 9% refused therapy due to physical and psychological discomfort, 2% wanted to become pregnant, 16% were lost to follow-up, 6% died from multimorbidity and old age. Three subjects (2%) developed cancer of the lung, breast or cervix uteri, possibly in relation to long-term MTX treatment. Altogether there were no deaths or life-threatening side-effects attributable to MTX treatment, and no cases of progressive liver cirrhosis apart from two extensive skin necroses due to overdosage (misunderstanding, suicidal attempt) that were treated successfully with citrovorum factor. Conclusion,Low-dose MTX (<15,20 mg/week) is an effective therapy for extensive and severe forms of psoriasis if patients are selected carefully and monitored regularly, particularly with respect to liver and bone marrow toxicity. This helps to reduce severe side-effects even during long-term treatment. Drug interactions must be avoided. MTX therapy according to the guidelines is relatively safe and still has a place in the systemic treatment of psoriasis with 40 years of experience and an acceptable safety record. [source] Drug interactions between mycophenolate and cyclosporinePEDIATRIC TRANSPLANTATION, Issue 3 2004Guido Filler MD First page of article [source] Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and Other Frequently Prescribed Medications: A ReviewTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Elinore F. McCance-Katz MD Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.,(Am J Addict 2009;19:4,16) [source] Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 aloneBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Juha Grönlund WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes. , So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS , Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone. , When both of CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. AIM The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone. METHODS A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated. RESULTS Paroxetine alone reduced the area under concentration,time curve (AUC(0,0,48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,,) of oxycodone increased by 2.9-fold (P < 0.001), and its Cmax by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo. CONCLUSIONS Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. [source] Effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Hyunmi Kim WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Woohwangcheongsimwon suspension has traditionally been used for the treatment and prevention of stroke, hypertension, palpitations, convulsions and unconsciousness in various Asian countries. , Woohwangcheongsimwon suspensions showed an inhibitory effect on CYP2B6 activity in vitro. Two terpenoids, borneol and isoborneol, are major constituents of woohwangcheongsimwon suspension, and show a competitive inhibition of CYP2B6 with Ki values of 9.5 and 5.9 µm, respectively. , Bupropion undergoes metabolic transformation to the active metabolite, 4-hydroxybupropion, primarily via CYP2B6 both in vivo and in vitro. It is often used as a CYP2B6 substrate for clinical drug,drug interaction studies. , Drug interactions may occur between woohwangcheongsimwon suspension and bupropion. WHAT THIS STUDY ADDS , Co-administration with woohwangcheongsimwon suspension did not alter the pharmacokinetics of bupropion or its metabolite, 4-hydroxybupropion. , Dosage adjustment of bupropion is unnecessary in patients concomitantly administered the highest recommended daily dose of woohwangcheongsimwon suspension. AIMS To examine the effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, formed via CYP2B6 in vivo. METHODS A two-way crossover clinical trial with a 2 week washout period was conducted in 14 healthy volunteers. In phases I and II, subjects received 150 mg bupropion with or without woohwangcheongsimwon suspension four times (at ,0.17, 3.5, 23.5 and 47.5 h, with the time of bupropion administration taken as 0 h) in a randomized balanced crossover order. Bupropion and 4-hydroxybupropion plasma concentrations were measured for up to 72 h by LC-MS/MS. Urine was collected up to 24 h to calculate the renal clearance. In addition, the CYP2B6*6 genotype was also analyzed. RESULTS The geometric mean ratios and 90% confidence interval of bupropion with woohwangcheongsimwon suspension relative to bupropion alone were 0.976 (0.917, 1.04) for AUC(0,,) and 0.948 (0.830,1.08) for Cmax, respectively. The corresponding values for 4-hydroxybupropion were 0.856 (0.802, 0.912) and 0.845 (0.782, 0.914), respectively. The tmax values of bupropion and 4-hydroxybupropion were not significantly different between the two groups (P > 0.05). The pharmacokinetic parameters of bupropion and 4-hydroxybupropion were unaffected by woohwangcheongsimwon suspension. CONCLUSIONS These results indicate that woohwangcheongsimwon suspension has a negligible effect on the disposition of a single dose of bupropion in vivo. As a result, temporary co-administration with woohwangcheongsimwon suspension does not seem to require a dosage adjustment of bupropion. [source] Synergistic interaction between trifluorothymidine and docetaxel is sequence dependentCANCER SCIENCE, Issue 11 2008I.V. Bijnsdorp Docetaxel is a microtubule inhibitor that has actions in the S and G2,M phase of the cell cycle. The pyrimidine trifluorothymidine (TFT) induces DNA damage and an arrest in the G2,M phase. TFT, as part of TAS-102, has been clinically evaluated as an oral chemotherapeutic agent in colon and gastric cancer. The aim of the present study was to determine the optimal administration sequence of TFT and docetaxel and to investigate the underlying mechanism of cytotoxicity. Drug interactions were examined by sulforhodamine B assays and subsequent combination index analyses, and for long-term effects the clonogenic assay was used. A preincubation with docetaxel was synergistic in sulforhodamine B (combination index 0.6,0.8) and clonogenic assays, and was accompanied by a time-dependent cell death induction (17,36%), the occurrence of polynucleation (22%), and mitotic spindle inhibition as determined by flow cytometry and immunostaining. Interestingly, administration of TFT followed by the combination displayed strong antagonistic activity, and was accompanied by less polynucleation and cell death induction than the synergistic combinations. Western blotting showed that the G2,M-phase arrest (25,50%) was accompanied by phosphorylation of Chk2 and dephosphorylation of cdc25c in the synergistic combinations. Together, this indicates that synergistic activity requires docetaxel to initiate mitotic failure prior to the activation of TFT damage signaling, whereas antagonism is a result of TFT cell cycle-arrested cells being less susceptible to docetaxel. Caspase 3 activation was low after docetaxel, suggestive of caspase-independent mechanisms of cell death. Taken together, our models indicate that combination treatment with docetaxel and TFT displays strong synergy when docetaxel is given first, thus providing clues for possible clinical studies. (Cancer Sci 2008; 99: 2302,2308) [source] Drug interactions in dermatological practiceCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2008H. L. Tey Summary Systemic drugs are increasingly used in the treatment of dermatological diseases. Due to the high prevalence of polypharmacy, dermatologists are increasingly faced with the complex problem of drug interaction. Unlike adverse drug reactions, which are often unpredictable, drug interactions can be avoided. This article presents the significant drug interactions that are encountered in clinical practice, with the interactions categorized into those involving antimicrobials, immunosuppressants, antimalarials and colchicine, retinoids and psychiatric medications. There are few commonly used drugs that often cause drug interactions. These include ciclosporin, azole antifungal drugs, erythromycin, sulfonamides and rifampicin, and dermatologists should be alert whenever encountering them. A section on interactions of drugs with health supplements, herbs and food is also included, in view of the increasing use of alternative and complementary therapies in many parts of the world. [source] Encephalopathy with combined lithium-risperidone administrationACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2008K. Boora Objective:, Lithium-neuroleptics induced encephalopathy is a rare drug interaction. Here I am reporting a patient who developed reversible encepatholopathy with lithium-risperidone combination. Method:, A single case report. Result:, A patient of bipolar disorder, who presented with manic symptoms with psychotic feature, started with a combination of lithium and risperidone. Within few days, the patient developed encepatholopathy, which reversed upon discontinuation of lithium and risperidone. Conclusion:, Combining lithium and neuroleptic is useful in treatment of bipolar disorder. However, encepatholapthy can be anticipated to result when lithium is used with high potency anti-psychotic such as haloperidol and risperidone and there are baseline EEG abnormalities. [source] The pharmacology of cilostazolDIABETES OBESITY & METABOLISM, Issue 2002Karsten Schrör Cilostazol (6-[4-(1-cyclohexyl- 1H -tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone; OPC-13013) is a 2-oxo-quinoline derivative with antithrombotic, vasodilator, antimitogenic and cardiotonic properties. The compound is a potent inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the cardiovascular system (IC50: 0.2 µm). In addition, there is inhibition of adenosine uptake, eventually resulting in changes in cAMP levels, dependent on the type of adenosine receptors (A1 or A2). Cilostazol inhibits platelet aggregation and has considerable antithrombotic effects in vivo. The compound relaxes vascular smooth muscle and inhibits mitogenesis and migration of vascular smooth muscle cells. In the heart, cilostazol causes positive inotropic and chronotropic effects. Most, if not all, of these actions are cAMP-mediated, including the modification of cAMP-controlled gene expression. Cilostazol decreases levels of serum triglycerides and causes some increase in HDL-cholesterol levels. The compound has a number of additional effects which might contribute to its overall clinical efficacy. Cilostazol undergoes intensive and finally complete hepatic metabolism via the cytochrome P450 systems. This might result in some drug interaction, i.e. with erythromycin and omeprazole. The half-life is approximately 10 h, resulting in about 2-fold accumulation of the drug during repeated administration. [source] REVIEW: Stress, alcohol and drug interaction: an update of human researchADDICTION BIOLOGY, Issue 1 2009Magdalena Uhart ABSTRACT A challenging question that continues unanswered in the field of addiction is why some individuals are more vulnerable to substance use disorders than others. Numerous risk factors for alcohol and other drugs of abuse, including exposure to various forms of stress, have been identified in clinical studies. However, the neurobiological mechanisms that underlie this relationship remain unclear. Critical neurotransmitters, hormones and neurobiological sites have been recognized, which may provide the substrates that convey individual differences in vulnerability to addiction. With the advent of more sophisticated measures of brain function in humans, such as functional imaging technology, the mechanisms and neural pathways involved in the interactions between drugs of abuse, the mesocorticolimbic dopamine system and stress systems are beginning to be characterized. This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from occasional drug use to drug dependence. We also review factors that contribute to different levels of hormonal/brain stress activation, which has implications for understanding individual vulnerability to drug dependence. Ultimately, these efforts may improve our chances of designing treatment strategies that target addiction at the core of the disorder. [source] Altered pharmacology in the intensive care unit patientFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2008Giovanni Zagli Abstract Critically ill patients, not infrequently present alterations of physiological parameters that determine the success/failure of therapeutic interventions as well as the final outcome. Sepsis and polytrauma are two of the most common and complex syndromes occurring in Intensive Care Unit (ICU) and affect drug absorption, disposition, metabolism and elimination. Pharmacological management of ICU patients requires consideration of the unique pharmacokinetics associated with these clinical conditions and the likely occurrence of drug interaction. Rational adjustment in drug choice and dosing contributes to the appropriateness of treatment of those patients. [source] Osteoporosis medication profile preference: results from the PREFER-US studyHEALTH EXPECTATIONS, Issue 3 2007Thomas W. Weiss DrPH Abstract Objective, To assess patient preferences for two osteoporosis medications. Design, Women aged 50+ were surveyed via the Internet to assess preferences for two osteoporosis medication profiles. Drug A and Drug B, consistent with ibandronate and alendronate, respectively, differed by: time on market (recently vs. 10 years), dosing frequency (monthly vs. weekly), effectiveness (not proven vs. proven to reduce non-spine or hip fracture after 3 years) and dosing procedure (60 vs. 30 min wait before eating/drinking). Each profile had the same out-of-pocket costs, side-effects, potential for drug interaction and spine fracture efficacy. Patients force ranked and rated the importance of each attribute. Subgroup comparisons included diagnosed vs. at-risk respondents and treated vs. untreated respondents. Results, Among the 999 respondents, Drug B was preferred by 96%. Effectiveness was ranked as the most important determinant of preference (79% ranked it #1) compared with time on market (14%), dosing procedure (4%) and dosing frequency (3%). Effectiveness had the highest mean importance rating on a scale of 1 (extremely unimportant) to 7 (extremely important): mean (SD) = 6.1 (1.8), followed by time on market: 4.7 (1.7), dosing procedure: 4.6 (1.4) and dosing frequency: 4.5 (1.4). No significant differences in profile choice were found across study subgroups. Conclusions, The drug profile showing reductions in non-vertebral and hip fracture risk was chosen by almost all respondents. Drug effectiveness was the most important determinant of preference, while dosing frequency was the least important determinant. Incorporation of patient preferences in the medication decision-making process could enhance patient compliance and clinical outcomes. [source] Interactions between protease inhibitors and acid-reducing agents: a systematic reviewHIV MEDICINE, Issue 6 2007L Béďque Objective The purpose of this article is to provide a systematic review of the available pharmacokinetic and clinical data on drug interactions between protease inhibitors (PIs) and acid-reducing agents, and their clinical relevance. Methods A literature search was performed using Medline and EMBASE, abstracts of the previous 2 years of major conferences were searched and the drug information service of the manufacturer of every currently available PI was contacted. All data were summarized, and verified by at least two authors. Results A total of 1231 references were identified, 22 of which were studies of pharmacokinetic interactions between PIs and acid-suppressive agents and a further 12 of which provided pharmacokinetic and/or clinical data. Conclusions Many pharmacokinetic studies show a lack of a drug interaction between at least one acid-reducing agent and most PIs. Little clinical information is available, except on interactions between atazanavir and acid-reducing agents. This is probably a consequence of the complexity of the interaction. [source] New once-daily formulation for trospium in overactive bladderINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2010C. Chapple Summary Aims:, We examined the relative efficacy and safety of trospium 20 mg bid and 60 mg extended release formulations and position this drug against other antimuscarinic agents. Methods:, Data were identified on the pharmacology and pharmacokinetics of trospium chloride. Key publications on trospium 20-mg and 60-mg clinical studies in patients with overactive bladder (OAB) were identified and efficacy and safety compared between these formulations as well as other antimuscarinic agents. Results:, Trospium offers the principal advantage over other antimuscarinic agents that, as it is a quaternary amine, it does not cross the blood,brain barrier and is therefore less likely to cause central nervous system effects observed with several other agents. Moreover, with its minimal liver metabolisation, independent of the main cytochrome pathways, trospium has a low risk of drug,drug interaction in patients taking multiple pharmacological agents. Trospium 60 mg ER is as effective as trospium 20 mg bid in improving the key outcome parameters associated with OAB, but with a lower rate of dry mouth, the most common side effect of these agents. Trospium has comparable efficacy and safety to the other antimuscarinic agents currently marketed. Discussion:, Good patient persistence with treatment has been reported with trospium. There are currently a large number of antimuscarinic drugs on the market without clear evidence to distinguish one agent from another in terms of efficacy, provided that an adequate dose is used in the clinical setting. Conclusion:, The new formulation of trospium is certainly worth considering as a pharmacological treatment of patients with OAB, particularly in the elderly, in whom one wants to avoid the potential for cognitive dysfunction. [source] Fatal peripheral neuropathy following FLA chemotherapyINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2004W. L. Osborne Summary We discuss a case with significant progressive peripheral neurological deterioration following administration of both fludarabine and cytarabine as part of the FLA (fludarabine and cytarabine) regime. Of particular interest is that toxicity only occurred during the second course of FLA and sixth course of Ara-C containing chemotherapy. At this point, a new antifungal agent had been commenced, suggesting a possible drug interaction enhancing the risk of known neurological toxicity with this regime. [source] Can sildenafil treat primary premature ejaculation?INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007A prospective clinical study Background: Recently, sildenafil has been demonstrated to be effective in treating premature ejaculation (PE). However, these studies ignored female factors and could not exclude the probability of drug interaction when combined with paroxetine. Therefore, the aim of this study was to evaluate the efficacy and safety of sildenafil alone in the treatment of primary PE, taking female factors into consideration. Methods: One hundred and eighty potent men with primary PE were randomly divided into three groups and followed up for 6 months. Group A were treated with 50 mg sildenafil as needed, group B with 20 mg paroxetine daily and group C with squeeze technique daily. Intravaginal ejaculatory latency time (IELT), PE grade, intercourse satisfactory score (ISS), frequency of intercourse, and adverse effects of drugs were recorded before treatment, and 3 and 6 months after treatment. Results: Compared with pretreatment, the three groups had significant differences in all the parameters after 3 or 6 months treatment, except the frequency of intercourse in Group C (all P = 0.00). However, there were no significant differences between 3 and 6 months. Compared with paroxetine and squeeze technique, after 3 or 6 months, sildenafil had significant differences in all the parameters (all P = 0.00). After 6 months, 1.7%, 18.3% and 36.7% patients in groups A, B and C, respectively, withdrew from the study and 86.7%, 60.0% and 45.0% patients, respectively, wanted to be treated further with the original administration, and this was statistically significant (both P = 0.00). Conclusion: Sildenafil is very effective and safe to treat PE, and has much higher efficacy than paroxetine and squeeze technique. [source] Clinical drug interactions in outpatients of a university hospital in ThailandJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2005B. Janchawee PhD Summary Background:, A clinical event is likely to occur in patients receiving a pair of drugs, that have the potential to cause an interaction. The occurrence of a clinical drug,drug interaction in outpatients of university hospitals in Thailand is unknown. Purpose:, To investigate the occurrence of a clinical event associated with drug,drug interactions in outpatients at a Thai university hospital. Methods:, A case,control study was established. The case was a sample group, randomly selected from a 1-year sample of outpatient prescriptions containing ,significance-1' potential drug,drug interactions, whereas the control was from the same year but with no potential drug interactions. Medical records of the cases and the controls were reviewed for an adverse event (AE) using a newly developed review form. The odds ratio of occurrence of the AE between the cases and the controls was determined. The AE was assessed for its possibility of being caused from a drug,drug interaction. Results:, The most common specific AE in both the cases and the controls was cough. An unplanned revisit to outpatient department or emergency room was found to be the most common general AE. The odds ratio of the occurrence of an AE in the cases, compared with the controls, was 1·495 (95% CI: 0·917,2·438). The possibility that the AEs resulted from drug interactions in the case group was nine ,probable' patients and 15 ,possible' patients, whereas that in the control group was eight ,possible' patients. The most common interacting drug pair was isoniazid,rifampin with an increase in serum hepatic enzymes as the corresponding AE. Conclusions:, Despite outpatients receiving drug pairs with a high potential for adverse interactions, the rate of occurrence of clinical drug interaction events was low. [source] Pharmacoepidemiologic study of potential drug interactions in outpatients of a university hospital in ThailandJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2005B. Janchawee PhD Summary Background:, Drug,drug interaction is a potential cause of adverse drug reactions. The incidence of such drug interactions in university hospitals in Thailand is unknown. Purpose:, To estimate the rate of potential drug,drug interactions in outpatients of a typical Thai university hospital, and to identify risk factors for such interactions in Thai patients. Methods:, One-year outpatients' prescription data were retrieved from the hospital computer records. Potential drug interactions were identified using the existing drug-interaction database system. Potential interactions within a specific prescription and involving drugs prescribed 1-, 3- and 7-day earlier were searched for. Possible associations between occurrence of an interaction and a patient's age and gender and the number of items on the prescription were explored. Results:, The overall rate of potential drug interactions was 27·9% with a maximal value of 57·8% at the Department of Psychiatry. The rate of the most potentially significant interactions was 2·6%, being the highest in the Department of Medicine (6·0%), with isoniazid vs. rifampin as the most common interacting combination. The rate increased with the patient's age and prescription size (P = 0·000). The odd's ratio of having at least one potential drug interaction was 1·8 (64·2%) when age increased by 20 years (P = 0·000) and 2·8 (165·7%) when another drug was added (P = 0·000). The rate of potential drug interactions was the same for both genders. The rate of potential drug interactions detected across prescriptions was higher than within prescriptions and was dependent on the time interval between prescriptions. Conclusions:, Potential drug interactions were common in our sample of patients. The rate of such interactions increased with the number of drugs prescribed and the patient's age. [source] | ||||||||||||||||||||||||||||||||||||||||