Risk Of Potential Interactions Research Articles

Drug Interactions in the Treatment of Chronic Heart Failure: Analysis of Clinical Guidelines

Background. According to Russian epidemiological studies, the prevalence of chronic heart failure (CHF) in the general population is high and amounts to 7–10%. Therapy of any disease, and especially chronic disease, is associated with the prescription of drugs. With the development of evidence-based medicine and implementation of its achievements in real clinical practice all over the world there is an increase in the number of prescribed drugs. This explains the high relevance of the problem of drug-drug interactions. Aims — analysis of interactions of drugs recommended for prescription to patients suffering from CHF. Methods. Based on the Clinical Guidelines (CG), all possible interdrug interactions of recommended medicinal products were analysed. Information on potential drug-drug interactions was obtained from the specialised website Drugs.com. Know more. Be sure (https://www.drugs.com/interactions/list/). Results. ACE inhibitors / ARA II / valsartan+sacubitril, beta-adrenoblockers and aldosterone antagonists are recommended as part of combination therapy for treatment according to CG for all patients with symptomatic heart failure (class II–IV) and reduced LV ejection fraction 40%. Amiodarone, verapamil and diltiazem are among the drugs not recommended for use in patients with the diagnosis of CHF. Also, according to clinical guidelines, HMG-CoA reductase inhibitors (atorvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, fluvastatin), direct renin inhibitors (heparin), COX-2 inhibitors (parecoxib, polmacoxib, celecoxib, etoricoxib) are among the unrecommended drugs in chronic heart failure.For ACE inhibitors, no adverse effects from interaction with beta-blockers have been identified. This combination is widely used and recommended by the CG. According to the “Major” type for ACE inhibitors with drugs indicated for use in CHF according to CG, 4 potential interactions were identified: with valsartan-sacubitril; angiotensin II receptor antagonists; with aldosterone antagonist (spironolactone); with loop and thiazide diuretics. Therefore, the appointment of angiotensin II receptor antagonists is carried out in case of ineffectiveness of initial therapy with ACE inhibitors, when changing the treatment tactics. These drugs are not used in combination with each other due to the risk of hyperkalemia. The prescription and use of diuretics while taking ACE inhibitors should be controlled by a physician also due to the risk of hyperglycaemia. In Moderate type, potential interactions with dapagliflozin, eplerenone, cardiac glycosides and heparin have been identified for ACE inhibitors. For beta-blockers, no potential Major-type interactions were identified with drugs from CG. Combinations with dapagliflozin, loop and thiazide diuretics, cardiac glycosides, spironolactone and ivabradine require special attention. It is recommended to avoid the combination of beta-blockers with valsartan. Of the recommended angiotensin II receptor antagonists, no risk of potential interactions with beta-blockers has been identified for candesartan and losartan.

Health disparity in the spread of COVID-19: Evidence from social distancing, risk of interactions, and access to testing

- To identify and assess whether three major risk factors that due to differential access to flexible resources might help explain disparities in the spread of COVID-19 across communities with different socioeconomic status, including socioeconomic inequalities in social distancing, the potential risk of interpersonal interactions, and access to testing. Analysis uses ZIP code level weekly COVID-19 new cases, weekly population movement flows, weekly close-contact index, and weekly COVID-19 testing sites in Southern California from March 2020 to April 2021, merged with the U.S. census data to measure ZIP code level socioeconomic status and cofounders. This study first develops the measures for social distancing, the potential risk of interactions, and access to testing. Then we employ a spatial lag regression model to quantify the contributions of those factors to weekly COVID-19 case growth. Results identify that, during the first COVID-19 wave, new case growth of the low-income group is two times higher than that of the high-income group. The COVID-19 case disparity widens to four times in the second COVID-19 wave. We also observed significant disparities in social distancing, the potential risk of interactions, and access to testing among communities with different socioeconomic status. In addition, all of them contribute to the disparities of COVID-19 incidences. Among them, the potential risk of interactions is the most important contributor, whereas testing accessibility contributes least. We also found that close-contact is a more effective measure of social distancing than population movements in examining the spread of COVID-19. - This study answers critically unaddressed questions about health disparities in the spread of COVID-19 by assessing factors that might explain why the spread is different in different groups.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Dietary Supplement Use and Interactions with Tamoxifen and Aromatase Inhibitors in Breast Cancer Survivors Enrolled in Lifestyle Interventions.

The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.

Abstract PS8-09: Dietary supplement use in a healthy eating and exercise lifestyle intervention in breast cancer survivors: The lifestyle exercise and nutrition (LEAN) study

Abstract Background: Dietary supplements (DS), defined as herbal preparations, vitamins and minerals (DSHEA Act 1994), are used by 70% of cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research 2018 Cancer Prevention Recommendations specify not to use DS to protect against cancer. There is some evidence that DS are linked to harmful outcomes, including increased mortality and breast cancer recurrence. DS have potential pharmacokinetic interactions via cytochrome P450 enzyme and pharmacodynamic interactions via estrogenic or hepatotoxic activity, which may increase or reduce clinical efficacy or potentiate adverse effects of Tamoxifen and Aromatase Inhibitors (AIs). This analysis examines baseline usage of DS and potential interactions with Tamoxifen and AIs among breast cancer survivors enrolled in the Lifestyle, Exercise, and Nutrition (LEAN) study, a randomized healthy eating and exercise lifestyle intervention. Methods: We examined the use of DS in 151 breast cancer survivors enrolled in the LEAN Study. Women with a body mass index (BMI) ≥ 25 kg/m 2 were randomly assigned to a 6-month healthy eating and exercise lifestyle intervention (n=93) or to usual care (n=58). At baseline and 6 months, we asked participants to self-report regular DS use, defined as at least 3 times a week for at least one month. The intervention group received evaluation and counseling of DS use by a Registered Dietitian (RD) with a Certified Specialty in Oncology Nutrition (CSO). Potential interactions of moderate and major ratings between DS with Tamoxifen and AIs (Letrozole, Exemestane and Anastrozole) were identified through the Natural Medicines Database by both a pharmacist specializing in oncology and a RD, CSO. Results: Out of 151 women, at baseline 120 (80%) reported using DS. Fifty-four different formulations were enumerated. The majority of women (72, 60%) were taking ≥ 3 formulations. One quarter of women (29, 24%) were taking ≥ 5 formulations (range = 1 - 20). Of the 54 formulations, 33% had potential interactions with Tamoxifen and/or AIs according to the Natural Medicines Database. Total interactions by medication were: 18 Tamoxifen, 14 Letrozole, 14 Exemestane, 9 Anastrozole. The majority of these interactions (87%) were associated with herbal preparations. Conclusions: Our findings are indicative of the high prevalence of DS use among breast cancer survivors and the potential risk of interactions with prescribed hormonal therapy. More research is needed to test if counseling from a RD, CSO can reduce DS use and ultimately lead to better outcomes due to fewer interactions with breast cancer treatments. Citation Format: ThaiHien Nguyen, Maura Harrigan, Courtney Mcgowan, Annette Hood, Fangyong Li, Brenda Cartmel, Leah Ferrucci, Melinda L Irwin, Tara Sanft. Dietary supplement use in a healthy eating and exercise lifestyle intervention in breast cancer survivors: The lifestyle exercise and nutrition (LEAN) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-09.

Magnesium and Drugs.

Several drugs including diuretics and proton-pump inhibitors can cause magnesium loss and hypomagnesemia. Magnesium and drugs use the same transport and metabolism pathways in the body for their intestinal absorption, metabolism, and elimination. This means that when one or more drug is taken, there is always a potential risk of interaction with the magnesium status. Consequently the action of a drug may be adversely affected by magnesium (e.g., magnesium, calcium, and zinc can interfere with the gastrointestinal absorption of tetracycline antibiotics) and simultaneously the physiological function of minerals such as magnesium may be impaired by a drug (e.g., diuretics induce renal magnesium loss). Given the ever-increasing number of drugs on the market and the frequency with which they are used, greater attention must be paid in daily medical and pharmaceutical practice focused in particular on the adverse effects of drug therapy on magnesium status in order to minimize the potential risk to the health of patients.

Nutraceutical-based Integrative Medicine: Adopting a Mediterranean Diet Pyramid for Attaining Healthy Ageing in Veterans with Disabilities.

Veterans with disability represent a big burden worldwide and often require long-term rehabilitation. Unhealthy dietary and lifestyle habits, including smoke and alcohol abuse, are common in veterans. In the context of integrative medicine approaches, the "complementary and alternative medicine" has been suggested for the management of chronic diseases. However, the potential risk of interaction between herbal products, dietary supplements and drugs must be considered in veterans. The Mediterranean diet has been suggested as a natural, non-pharmacological nutraceutical for healthy ageing. Although there is a broad consensus on the positive effect of plant foods consumption, the presence of glucosinolates, flavonoids and furanocoumarins in some plant foods and beverages must be taken into consideration owing to their potential interfering with drugs metabolism and bioavailability. Albeit seasonality could ensure the maintenance of the single dose of phytochemical below that at which adverse effects in some individuals genetically predisposed or unpleasant drug interactions in diseased subjects can occur, a personalized nutrition is recommended in veterans who are under treatment for comorbidities. Furthermore, sports practice can lead veterans with motor disabilities and mental impairments to excel in some disciplines, giving rise to the phenomenon of the Paralympics and the development of "recreational therapy". Moreover, outdoor lifestyle, through vitamin D synthesis, and conviviality, improving socialization, could account for the Mediterranean lifestyle health benefits. In this work, we propose for veterans a Mediterranean Pyramid, which could be the basis for integrative medicine for veterans with disabilities, patient-centered approaches and interprofessional (including physical medicine and rehabilitation clinicians, pharmacists and nutritionists) interventions.

O-45 The influence of training program on the functionality of respiratory system

For each individual must be appropriate life style modelling of the respiratory system functionality as well necessity for physical activity, training program, especially for amateur and professional athletes. The influence of variable factors gives implications to the amateur athletes’ body and respiratory system- health condition, supplements or necessary treatment, physical working capacity of the body, physical activity with increased function of respiratory system, cardiopulmonary interdependence, hydration, fitness level, physical abilities, training or competition period, training process and ambience. High level functionality of respiratory system decreases risk of potential interaction with physical load connected diseases. To better assess functionality of respiratory system in amateur sports there is an importance of sports doctors or coaches advices to adjust suitable training programs. Objective To assess the influence of training program intensity on the functionality of respiratory system using cardiopulmonary exercise testing for adult amateur athletes. Methods The research was established in Sports laboratory, Ltd. 1100 adult amateur athletes (68%, n-750men), who does high dynamic load kind of sports, such as rowing, swimming, cycling, running and sports games, aged 25-50 years, underwent maximal cardiopulmonary exercise testing on ISO certified Master screen CPX system with breath by breath gas exchange and flow/volume measurements analysis during the rest, different phases of the physical load, including maximal load and recovery. Amateurs were divided in groups: 1.group (n-375men) and 3.group (n-150 women) with training program of professionals 300-600 load min/week (>10 years); 2.group (n-375men) and 4.group (n-200women) with training program of amateurs 90-240 load min/week (>5 years). Estimated indices (compared with calculated age, gender, height and weight dependent predicted values(PV)): breathing rhythm, breathing frequency(ƒ), ventilation(V E ), inspiration(V Tin ), expiration(V Tex ), oxygen uptake(V O2 ), ventilatory oxygen and carbon dioxide coefficients(V E /V O2 ; V E /V CO2 ). Standard descriptive statistical analyses were conducted (SPSS version22.0 software (IBM SPSS,Corp.,Armonk,NY)). Results During the physical load arrhythmic and forced breathing was registered 46% men and 53% women amateur athletes. 1.group men reached 15.3%, 3.group women 28.5% higher maximal load, than 2. and 4.groups athletes (p Flow/volume measurements: ƒ,max were rare than PV for all four groups: 1.group-7%; 2.group-14.3%; 3.group-11.9%; 4.group-19% (p E, max were 113 ± 22 L/min for 1.group; 2.group-103 ± 20 L/min; 3.group-77 ± 17 L/min; 4.group-67 ± 15 L/min (p The functional gas exchange measurements: V O2 max were higher than PV for 1.group-10.7%, reached 41.23 ± 8.13 mL/min/kg; 2.group-32.3%, reached 34.00 ± 7.09 mL/min/kg; 3.group-19.9%, reached 35.71 ± 6.89 mL/min/kg (p E /V O2 max and V E /V CO2 max than athletes with training program of amateurs (p Conclusion The estimation of respiratory system values shows statistical differences between research groups in all testing phases. The intensity of training program gives significant influence to respiratory system functionality (ƒ, V E, V O2 ). Independently of training program intensity inspiration, expiration volumes were in similar values. Metabolic equivalent was lower than PV in all groups, except men amateur athletes with training program of professionals, and it marks significant point of view to this measurement, because of other indices were exceeded. The authors of research continue to determine the value of PV for amateur athletes.

Uso de psicofármacos en un grupo de adultos mayores de Rosario, Argentina

Objective: classify the type of psychoactive drugs used in elderly in a Clinical Research and Assistance Center. Methods: descriptive and cross-sectional study, carried out from January 2, 2011 to March 1, 2014; outpatients over 60 years old who attended the Assistance Center and Integral Research Clinic (caici), in Rosario, Argentina were included; and those who signed the respective informed consent. Data were analyzed using descriptive statistical techniques. Results: from a total of 667 patients, the sample only included 235. The highest age group of consumption was from 60 to 70 years (55%). Benzodiazepines were consumed in 67%, 3% antipsychotics and antidepressants 30%. Specialists in medical clinic prescribed 70% of benzodiazepines and antidepressants 20%. All antipsychotic drugs were prescribed by psychiatrists; 35 had a potential risk of interaction; the combinations were benzodiazepines and antidepressants. There was no risk of serotonin syndrome in the indication of citalopram and desvenlafaxine; no alterations were observed by the combination of benzodiazepines from the same group and the same mechanism of action. Conclusions: it was observed in this work an increase in the consumption of psychotropic drugs in patients older than 60 years, mainly in those who do not continue with an active life; regarding the gender there is a higher percentage in females. The majority of the patients received indication of benzodiazepines by their clinical physician.

Frequency of coprescription and potential risk of bronchospasm in Colombian patients users of topical antiglaucomatous betablockers and bronchodilators

Background: Cardiovascular and respiratory effects of adrenergic agonists used in diseases like chronic obstructive pulmonary disease (COPD), and β-blockers used in glaucoma generate competitive antagonism on the same adrenergic receptor when used simultaneously with the aggravation that the β-blockers can precipitate bronchospasm. Objective: Determine de frequency of coprescription and potential risk of interaction between bronchodilators and topical antiglaucomatous β-blockers for glaucoma in a database of Colombian patients. Methods: Cross-sectional study in patients older than 40 years treated for bronchial disorders and glaucoma between January 1 and October 31, 2012. We used information about 6.2 million population database of individuals enrolled in Health System of Colombia. In the database it was assessed all prescription records of topical β-blockers and any bronchodilators and the frequency of potential risk of developing drug-induced bronchospasm. The identified patients were informed to the physician responsible to the health attention. Results: We found 1756 patients were receiving topical β-blockers and bronchodilators. Most were women (63.2 %), mean age 73.3 ± 11.1 years, in 61 cities. The antiglaucoma drugs more employees were: timolol (67.5 % of patients), timolol/dorzolamide (18.8 % of patients) and bronchodilators: salbutamol (43.8 % of patients) and ipratropium (41.8 % of patients). The more frequent risk associations of bronchospasm were: salbutamol + timolol (n = 890, 50.6 % of patients), ipratropium bromide + timolol (n = 827, 47.1 %) salbutamol + timolol + dorzolamide (n = 258, 14.6 % of patients) and ipratropium bromide + timolol + dorzolamide (n = 255, 14.5 % of patients). Conclusions: The database research of Negative Outcomes Associated with Medication is useful to know problems in prescription of many therapies. There are potential interactions between antiglaucoma drugs and bronchodilators that increase the risk of precipitating bronchospasm in patients who present asthma, COPD and glaucoma in Colombia. Implementing strategies that link drug dispensers and medical insurers can reduce risks associated with the medication.

Expression and induction by dexamethasone of ABC transporters and nuclear receptors in a human T-lymphocyte cell line

The efficacy of drugs acting within lymphocytes, like antiretroviral drugs in the treatment of HIV infection, depends on their intracellular concentrations modulated by efflux proteins like ABCB1 (P-glycoprotein). In lymphocytes, two glucocorticoids, prednisone and prednisolone, have been shown to induce ABCB1 activity. Yet, no data exist regarding dexamethasone (DEX). We report the modulation of ABC transporters and nuclear receptors’ expression by DEX in a commonly used model of human lymphocytes. CCRF-CEM cells were exposed to DEX (100 nM, 2 μM) for 24 to 72 hours. ABCB1 activity was measured using DiOC6 efflux in flow cytometry. Gene expression levels were quantified by qRT-PCR. ABCB1 activity and mRNA expression increased with DEX concentrations and incubation times. DEX (1 μM, 24 h) increased significantly ABCB1 and GR mRNA expression levels by around 8- and 3·5-fold, respectively (P<10−6). ABCB1 induction by DEX in CCRF-CEM cells suggests a potential risk of interaction in lymphocytes when associating DEX to ABCB1 substrates in antiretroviral multitherapies in vivo.

Transdermal Contraceptive Patches

Many contraceptive methods have been developed for fertility regulation, either reversible or irreversible, in males and females. Oral contraceptives have been considered the most popular form of reversible contraception. However, they must be taken consistently, on a daily basis for 21 or 28 days of each menstrual cycle, in order to achieve the maximal outcomes of contraception. Moreover, their contraceptive efficacy has been reportedly affected by their interactions with many drug products taken concurrently for other conditions. To resolve the dilemma of daily compliance and the risk of potential interactions with drugs taken orally, several non-traditional delivery systems have been developed to permit contraceptive agents and their combinations to be administered via a non-oral route, and also at a lesser frequency of administration, so as to enhance treatment compliance, maximize therapeutic outcomes, and minimize adverse effects. One typical example is the successful development of the ethinylestradiol/norelgestromin patch for achieving contraception in females via transdermal delivery. With topical application on intact skin, each patch delivers a combination of norelgestromin and ethinylestradiol for a week. With a treatment schedule of 3 weeks with a patch on and 1 week without a patch for each menstrual cycle, the ethinylestradiol/norelgestromin patch has achieved a clinical efficacy that is considered bioequivalent to oral contraceptives (with an unintended pregnancy rate of 0.8% per woman-year for the patch versus 0.1% per woman-year for the combined oral contraceptive).Stimulated by the marketing success of the ethinylestradiol/norelgestromin transdermal contraceptive patch, and a growing recognition of the therapeutic benefits realized by delivering an orally inactive progestin via a transdermal route, other transdermal drug delivery systems (DDS), such as transdermal gels and a metered-dose transdermal spray system, have also been developed. Further transdermal contraceptive patches have also been developed. One of these is similar to the ethinylestradiol/norelgestromin patch, in that it is fabricated from an adhesive polymer matrix diffusion-controlled DDS; however, it has a two times smaller patch size (to minimize localized reactions at the application site). This was made possible by substituting norelgestromin with a more potent progestin called gestodene, that has a higher skin permeation rate. The other transdermal patch that has been developed employs a microreservoir partition-controlled delivery system, to provide dual-controlled delivery of estradiol (a natural estrogen) and levonorgestrel (another potent synthetic progestin) at constant rates (zero-order kinetics). Clinical studies have demonstrated that these two new patch systems may be attractive alternative forms of contraception, since ovulation inhibition has been achieved in all subjects who wear the transdermal patch for 3 weeks, replacing it on a weekly basis.A transdermal gel has been formulated to contain elcometrine, which has a progestational potency that is 100 times that of progesterone but is orally inactive, in an alcoholic solution. Preliminary clinical studies have indicated that suppression of ovulation was achieved in the majority of subjects receiving daily application of the transdermal gel. To address the problems associated with the dosing accuracy of the transdermal gel, due to difficulty controlling the area and size of the application site, the feasibility of delivering the transdermal gel from a metered-dose transdermal spray system is currently under evaluation by the Population Council.

Co-prescription of cytochrome P450 2D6/3A4 inhibitor-substrate pairs in clinical practice. A retrospective analysis of data from Norwegian primary pharmacies

Inhibition of cytochrome P (P450) (CYP) enzymes, in particular CYP3A4 and CYP2D6, is an important drug-interacting mechanism. The objective of our study was to assess how frequently CYP3A4 and CYP2D6 inhibitors are co-prescribed with substrates of the respective enzymes. Included inhibitors were clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole and nefazodone (CYP3A4 inhibitors) and bupropion, fluoxetine, paroxetine and terbinafine (CYP2D6 inhibitors). The inhibitors were combined with substrates shown to be pharmacokinetically sensitive towards inhibition (190 drug pairs in total). Lists of patients receiving inhibitors and substrates were drawn from prescription databases (approximately 43,500 patients) of three Norwegian primary pharmacies during a 6-month period (July 2002 to January 2003). The lists were matched on name and date of birth to identify patients using drug pairs. Concurrent use was made probable from dates of purchase and drug profiles. Inhibitors were prescribed to 2,062 patients. Altogether, 369 events of substrate co-prescription were registered. The highest frequencies of co-prescribed substrates were found for paroxetine (101 events per 267 patients, 38%), fluoxetine (36 events per 110 patients, 33%) and clarithromycin (59 events per 242 patients, 24%). The drugs most often detected in combination with inhibitors were codeine (116 events) and metoprolol (38 events) for CYP2D6 and zopiclone (45 events) and simvastatin (26 events) for CYP3A4. Several commonly used CYP2D6 and CYP3A4 inhibitors are frequently co-prescribed with substrates in Norwegian clinical practice. Alertness when inhibitors are prescribed would aid physicians and pharmacists to detect many drug combinations with potential interaction risk.

Transport screening of drug cocktails through an in vitro blood-brain barrier: is it a good strategy for increasing the throughput of the discovery pipeline?

The objective of the current study was to investigate whether blood-brain barrier (BBB) permeability studies in vitro could be accelerated by running several compounds together in the same experiment. To address this question, we compared the transport of six compounds run separately with the results of the same compounds run together (cocktails). The study clearly demonstrated that the outcome of the experiments were totally different depending on the strategy used. Furthermore, the study highlights the importance of having the resistance to drug transport offered by filters without cells under control, as the filter membrane itself can be the rate-limiting step for some compounds; in addition, there is always a potential risk of interactions between molecules in cocktails as well as drug-drug interaction at the level of BBB transporters. In this study, the presence of several P-glycoprotein substrates in the drug cocktail was found to cause breakdown of the BBB. The results demonstrate that unless a strategy that involves running several compounds in the same experiment is properly validated, the results are of little predictive value.

Exposure to potential drug interactions in primary health care

Harmful drug interactions may occur if one drug alters the effect of another drug. During the course of one year, about one-third of the population are exposed to the concurrent use of two or more drugs (polypharmacy). On average, 15% of individuals with polypharmacy are exposed to drugs carrying a risk of potential interactions. Elderly patients exposed to polypharmacy are at highest risk and should therefore be kept under intensified monitoring. Objective - To analyse the prevalence of potential drug interactions, and to identify patients particularly prone to drug interaction. Design - Database study (Odense University Pharmacoepidemiologic Database). Setting - Individuals exposed to polypharmacy in 1999 were examined for potential drug interactions. Subjects - Inhabitants of the County of Funen (n=471 t 732). Main outcome measures - Prevalence of potential drug interactions. Results - One-third of the population were exposed to polypharmacy and among these 15% were exposed to drugs carrying a risk of harmful interaction. Among the elderly with polypharmacy, 25% aged 60-79 years and 36% over 80 years received drugs carrying the risk of interaction. Among individuals exposed to potential drug interaction, 62% were exposed only to one drug interaction and 38% to two or more different drug interactions. The drugs accounting for the highest number of potential interactions were diuretics, NSAIDs, ACE-inhibitors, digoxin, oral antidiabetics, calcium channel blockers, anticoagulants and beta-blockers. When focusing only on major drug interactions, potassium-sparing diuretics and oral anticoagulants were the most frequently involved drugs. Conclusion - Elderly patients exposed to polypharmacy should be kept under intensified monitoring as they are at increased risk of clinically significant drug interactions.

Micronutrient interactions: effects on absorption and bioavailability

A potential risk of interactions between micronutrients affecting absorption and bioavailability has to be considered in any supplementation or fortification strategy. At levels of essential micronutrients present in foods, most micronutrients appear to utilise specific absorptive mechanisms and not be vulnerable to interactions. In aqueous solutions and at higher intake levels competition between elements with similar chemical characteristics and uptake by non-regulated processes can take place. These interactions have clearly been demonstrated in experimental absorption studies and to some extent have been confirmed in supplementation studies. Negative effects of iron supplementation on indices of zinc and copper status and of zinc supplementation on iron and copper status have been reported. In contrast, the negative effect of calcium on iron absorption has not been confirmed in long-term supplementation studies. Ascorbic acid has a strong iron absorption promoting potential and in iron deficient populations ascorbic acid supplementation improves iron status. Thus, ascorbic acid supplements or an increased intake of ascorbic acid rich foods could have important public health implications, especially in populations subsisting on a mainly plant food based diet. The effect of poor status of a given micronutrient on absorption and utilisation of other micronutrients should also be considered while developing strategies to improve micronutrient status in a population. Awareness of these interactions, combined with a balanced evaluation of the dietary intake of the population with regard to absorption promoting and inhibiting substances and the risk for multiple deficiencies, could lead to more effective strategies to improve micronutrient status.

Uso inadecuado de fármacos junto con alcohol en un consultorio rural

To determine the prevalence of the joint use of alcohol and medication with the risk of interaction with alcohol, the social and personal features of patients most likely to use the two combined, and the extent of anti-alcohol medical counselling of these patients. Prevalence study. Primary care. Rural local clinic at Trigueros (Huelva). 581 histories of patients over 14, started between October 1993 and December 1996. From the clinical histories we obtained the social and personal features, toxic habits, type and number of medicines prescribed, and whether or not there was medical counselling on alcohol consumption. Potential interactions were looked for through the list provided by Mengual Sandra and Gila Azañedo. 10.15% (95% CI, 7.8-12.9) of the subjects consumed at the same time medication with risk of interaction and alcohol. Males (OR = 7.1), over-65s (OR = 4.9), married people (OR = 3.1) and smokers (OR = 2.3) were more likely to combine alcohol and at-risk medication. 6.8% of the patients with potential risk of interaction were counselled against alcohol. The simultaneous use of alcohol (as drinks or a component of medicine) and at-risk drugs is a common reality in primary care. Men, the over-65s, smokers and married people are at greater risk. Medical counselling of patients at potential risk of interaction is quite rare, although it is greater than of drinkers who do not take at-risk medicines.

Difficulties in assessing drug/food interactions from chart audit in an elderly Barbadian sample group.

The aim of this study was to examine the prevalence of potential drug/food interactions among 290 elderly Barbadian outpatients. These findings indicate that chart audit is insensitive to definite interactions but was able to detect the prevalence of potential interactions (1.38 per outpatient). The risk of potential interactions was significantly higher among outpatients who were older, female, and those who used a larger number of prescribed medications. There were no significant differences in the prevalence of potential interactions among diabetics and nondiabetics. The findings indicate that the absence of relevant data on patients' symptoms, and anthropometric and laboratory measures in more than 80% of patients' charts makes it impossible to assess the prevalence of definite drug/food interactions from chart audit. Weight changes, nutrient levels, and symptoms were the most frequently missing data. Chart audit is therefore an invalid and unreliable approach to estimate definite drug/food medications.