Potential Pharmacological Interactions Research Articles

Dyslipidemia and Cardiovascular Prevention in the Elderly: A Balance between Benefits and Risks of Statin Treatment in a Specific Population.

Atherosclerotic Cardiovascular Diseases (CVD) are among the most relevant causes of morbidity and mortality worldwide, especially in aged people. Statins are one of the leading pharmacological interventions against atherosclerosis and are widely used to reduce the risk of occurring coronary artery diseases and related outcomes in both primary and secondary prevention. The management of chronic diseases is improved considerably over time, leading to an increase in life expectancy despite heavier comorbidity-related burdens in the elderly. The paper focused on the role of statins in the management of atherosclerosis and related burdens in elderly patients. Statins are essential in reducing the risk of CVD in secondary and primary prevention, particularly in high-risk individuals. Guidelines encourage using specific algorithms with age-specific cutoffs to assess individual cardiovascular risk irrespective of baseline age, as the expansion of life expectancy produces favorable effects of statin treatment in those over 70. Besides the estimation of baseline CV risk, a specific age-related assessment is also necessary before prescribing statin treatment in aged people focusing on frailty, potential pharmacological interactions due to polypharmacotherapy, cognitive impairment, and background chronic comorbidities, such as diabetes mellitus. Before starting statin therapy, an accurate choice of type and dose of statins is needed as potential adverse events are more prevalent with high-dose than low-to-moderatedose regimens and with lipophile than hydrophile statins (e.g., potential implication on intra-cerebral cholesterol metabolism). Despite possible adverse events, elderly patients should receive statins, when appropriate, to avoid the first occurrence of recurrent cardiovascular events and related burdens.

Prevalence of Potential Pharmacological Interactions in Patients Undergoing Systemic Chemotherapy in a Tertiary Hospital.

Introduction: Pharmacological interactions are frequently observed in patients with chronic diseases, and their occurrence is proportional to the amount of medication used daily. Patients undergoing chemotherapy treatment commonly have comorbidities, which favor a greater prevalence of polypharmacy, increasing the risk of drug interactions. Therefore, the aim of this study was to estimate the prevalence of drug interactions in patients undergoing intravenous chemotherapy treated at a hospital oncology service in southern Brazil. Methods: This was an observational study with a cross-sectional design that was carried out with the analysis of secondary data obtained through the review of medical records. The population assessed consisted of all cancer patients who received intravenous chemotherapy from October to December 2020. Results: Out of the 297 patients included in the study, 231 (77.8%) had at least 1 potential pharmacological interaction. In total, 1044 drug interactions were found that were classified according to severity, resulting in 18 (1.7%) contraindicated drug-drug interactions (DDI), 699 (67%) severe, 281 (26.9%) moderate, and 46 (4.4%) minor interactions. There was an association between polypharmacy and the prevalence of drug interactions. Conclusion: The results demonstrate that a large percentage of patients undergoing chemotherapy are susceptible to drug interactions. Thus, it is necessary that prescribers consider all drugs used by patients and, when possible, prescribe alternative drugs that have less potential for interaction in order to prevent drug interactions adverse effects and provide a better prognosis for patients.

Intrathecal Baclofen Pump Perioperative Management: Case Report and Literature Review

The use of intrathecal baclofen pumps (ITBP) has become increasingly common worldwide for the treatment of severe spasticity. Increased prevalence of patients using ITBPs makes encounters ever more common with surgical teams, these surgical interventions may be related to ITBP manipulation or completely unrelated to these devices. The anesthetist must be familiar with the normal functioning of ITBPs and be aware of baclofen pharmacokinetics in the cerebrospinal fluid, the occurrence of baclofen overdosing or withdrawal, and the potential pharmacological interactions between baclofen and drugs commonly used intraoperatively.

The Manifesto of Pharmacoenosis: Merging HIV Pharmacology into Pathocoenosis and Syndemics in Developing Countries.

Pathocoenosis and syndemics theories have emerged in the last decades meeting the frequent need of better understanding interconnections and reciprocal influences that coexistent communicable and non-communicable diseases play in a specific population. Nevertheless, the attention to pharmacokinetic and pharmacodynamics interactions of co-administered drugs for co-present diseases is to date limitedly paid to alert against detrimental pharmacological combos. Low and middle-income countries are plagued by the highest burden of HIV, tuberculosis, malaria, and helminthiasis, and they are experiencing an alarming rise in non-communicable disorders. In these settings, co-infections and comorbidities are common, but no tailored prescribing nor clinical trials are used to assess and exploit existing opportunities for the simultaneous and potentially synergistic treatment of intertwined diseases. Pharmacoenosis is the set of interactions that take place within a host as well as within a population due to the compresence of two or more diseases and their respective treatments. This framework should pilot integrated health programmes and routine clinical practice to face drug–drug interaction issues, avoiding negative co-administrations but also exploiting potential favourable ones to make the best out of the worst situations; still, to date, guiding data on the latter possibility is limited. Therefore, in this narrative review, we have briefly described both detrimental and favourable physiopathological interactions between HIV and other common co-occurring pathologies (malaria, tuberculosis, helminths, and cardiovascular disorders), and we have presented examples of advantageous potential pharmacological interactions among the drugs prescribed for these diseases from a pharmacokinetics, pharmacodynamics, and pharmacogenetics standpoint.

Dietary supplement use in ambulatory cancer patients: a survey on prevalence, motivation and attitudes

PurposePatients with cancer often believe dietary supplements (DS) such as micronutrients and botanical products to be health supporting and non-toxic despite growing concerns regarding potential pharmacological interactions. Studies on the prevalence of DS use among patients with cancer are heterogeneous and mainly conducted at university-based cancer centers. This survey focused on a particular cancer patient group treated in an ambulatory setting without regular access to professional nutritional counselling.MethodsPatients with a history of cancer or hematological malignancy were included in this survey. A self-reported questionnaire was used to evaluate the different aspects of DS use, changes in dietary habits and patients’ demographic characteristics.ResultsAlmost every second patient reported using DS (47.2%). Women (56.3%), patients with an academic degree (56.0%) and non-smokers (84.8%) were more inclined to use DS. Along with magnesium (16.6%), calcium (14.3%), multivitamins (12.0%) and vitamin C (9.4%), use of herbal supplements (12.6%) was common. Women (84.8% vs. 74.9% of men, p = < 0.001) and patients younger than 65 years (84.4% vs. 77.2% of patients > 65 y, p = 0.002) sought dietary advice more often. Support of the immune system was the main reason for DS use (26.4%) and a relevant number of patients (49.6%) reported to have changed their dietary habits following cancer diagnosis.ConclusionDS use is common among patients with cancer treated in an ambulatory setting. This finding should encourage oncologists to implement detailed questioning about DS use and dietary habits to prevent potential interactions and offer substantial advice.

Ketamina eta esketaminaren erabilera depresioerresistentea tratatzeko: etorkizunerako erronkak

Nahasmendu depresiboak osasun publikoko arazo handienetako bat bilakatu dira azken urteotan, ez bakarrik bizi-kalitatean duten eraginagatik, baita tratamendu antidepresiboaren erantzun partzial edo erantzun ezagatik ere. Hori dela eta, (R,S)-ketaminaren (ketamina) efektu antidepresibo azkarra eta eraginkorra azken hamarkadetako aurkikuntza garrantzitsuenen artean dago psikiatria arloan. Orain arteko entseguetan ketaminaren zain barneko bidea gailendu den arren sudur bideko administrazioa aukera erabilgarri eta segurutzat jo da. Hori dela eta, FDAk (Food and Drug Administration) eta EMAk (European Medicines Agency) S-ketamina (esketamina) baimendu dute Spravato izen komertzialarekin merkaturatutako sudur-lainoztagailurako soluzio bezala, depresio erresistentea tratatzeko, farmako horren merkaturatze-baimena sostengatzen duten entsegu klinikoak epe luzekoak ez diren arren. Horregatik, epe luzeko segurtasun-profila ikertzea premiazkoa da, eta, testuinguru berean, baita administrazio-protokolo errepikatuen egokitasuna ere. Izan ere, ketaminak farmako antidepresibo batzuekin eta bentzodiazepinekin izan ditzakeen elkarrekintzak ebaluatzea gomendatzen da, tratamenduaren eragin antidepresiboa baldintza dezaketelako. Ildo horretan, orain arte egindako entseguen diseinuaren aldakortasuna kontuan hartzeko ezaugarria litzatekeela proposatu da. Izan ere, entsegu batzuetan, tratamendu antidepresibo gehigarria baztertzen da, eta beste batzuetan, berriz, mantendu egiten da; aldakortasun metodologiko horrek tratamendu antidepresiboaren eraginkortasuna alda dezake. Ondorioz, uka ezina da epe luzerako entsegu klinikoak egiteaz gain merkaturatze ondorengo farmakozaintza-azterlanak ere nahitaezkoak direla ketaminaren eta esketaminaren segurtasuna eta eraginkortasuna epe luzera bermatzeko.

Potential drug interactions and inappropriate medications prescribed for primary health care users

Objectives: To analyze potential pharmacological interactions and drugs potentially inappropriate for the elderly in users of primary care of the Unified Health System. Methods: This is a cross-sectional study with individuals aged 18 years or over, who were approached at the health facilities of the city of Divinópolis, MG, at which time a home visit was scheduled. A structured questionnaire on drug use was applied and drug interactions were analyzed in Drugs.com® sources, Micromedex®, bulletin of the Brazilian Health Regulatory Agency (ANVISA). Only the frequencies of serious interactions were analyzed. Potentially inappropriate drugs for elderly people (MPI) were identified by the Beers Criterion (2015) and the Brazilian Consensus on Potentially Inappropriate Medications for the Elderly (2016). The Mann-Whitney test was performed to compare the medians of the analyzed variables. Results: Among the study participants, 55% were elderly. Comparing them with the adult population, it was observed that the number of medications and potential drug interactions were significantly higher (p &lt;0.05) among patients 60 years of age or older. Considering only the elderly, 77.3% used at least one MPI, according to the Beers Criterion. Conclusion: It was found that the vast majority of primary care users use at least one inappropriate drug and, when compared to adults, are more exposed to polypharmacy and potential drug interactions.

Cannabidiol and Non-Steroidal Anti-Inflammatory Drug Interactions: A Case of Drug-Induced Aseptic Meningitis

Cannabidiol (CBD) and other marijuana derivatives are being more widely used in the medical community by people in an attempt to alleviate a variety of symptoms. While these products have shown promise in their analgesic properties, little is known about the potential pharmacological interactions of these and other drugs. We present a case of a 57-year-old Caucasian woman who presented with altered mental status, ataxia, left-sided numbness, and slurred speech. An extensive workup was completed and found to be largely unremarkable, though a thorough history revealed that her symptoms were likely caused by concurrent use of CBD and non-steroidal anti-inflammatory drugs (NSAIDs) resulting in drug-induced aseptic meningitis. The benign nature of CBD makes it a promising avenue for pain relief. Physicians and patients should be informed about the potential drug-drug interactions of CBD and other medications. J Neurol Res. 2020;10(4):132-135 doi: https://doi.org/10.14740/jnr598

Temozolomide and Other Alkylating Agents in Glioblastoma Therapy.

The alkylating agent temozolomide (TMZ) together with maximal safe bulk resection and focal radiotherapy comprises the standard treatment for glioblastoma (GB), a particularly aggressive and lethal primary brain tumor. GB affects 3.2 in 100,000 people who have an average survival time of around 14 months after presentation. Several key aspects make GB a difficult to treat disease, primarily including the high resistance of tumor cells to cell death-inducing substances or radiation and the combination of the highly invasive nature of the malignancy, i.e., treatment must affect the whole brain, and the protection from drugs of the tumor bulk—or at least of the invading cells—by the blood brain barrier (BBB). TMZ crosses the BBB, but—unlike classic chemotherapeutics—does not induce DNA damage or misalignment of segregating chromosomes directly. It has been described as a DNA alkylating agent, which leads to base mismatches that initiate futile DNA repair cycles; eventually, DNA strand breaks, which in turn induces cell death. However, while much is assumed about the function of TMZ and its mode of action, primary data are actually scarce and often contradictory. To improve GB treatment further, we need to fully understand what TMZ does to the tumor cells and their microenvironment. This is of particular importance, as novel therapeutic approaches are almost always clinically assessed in the presence of standard treatment, i.e., in the presence of TMZ. Therefore, potential pharmacological interactions between TMZ and novel drugs might occur with unforeseeable consequences.

Terpinen-4-ol inhibits the growth of Sporothrix schenckii complex and exhibits synergism with antifungal agents.

Aim: This study investigated the effect of terpinen-4-ol against Sporothrix schenckii complex and its interactions with antifungals. Materials & methods: The antifungal activity of terpinen-4-ol was evaluated by broth microdilution. The potential effect on cellular ergosterol concentration was evaluated by spectrophotometry. The antibiofilm activity was evaluated by violet crystal staining and XTT reduction assay. The potential pharmacological interactions with antifungals were evaluated by the checkerboard assay. Results: terpinen-4-ol (T-OH) showed minimal inhibitory concentrations ranging from 4 to 32mg/l decreasing cellular ergosterol content and presented a SMIC ranging from 64 to 1024mg/l for Sporothrix spp. The combinations of T-OH with itraconazole or terbinafine were synergistic. Conclusion: T-OH has antifungal activity against Sporothrix spp. and acts synergistically with standard antifungals.

Timing Strategies of Direct-Acting Antivirals and Biologics Administration in HCV-Infected Subjects with Inflammatory Bowel Diseases.

Background: In the last years, inflammatory bowel disease (IBD) and hepatitis C virus (HCV) infection management has completely changed. However, the role of direct-acting antivirals (DAAs) and the correct timing of antiviral drugs administration in IBD patients needing biologics has not been evaluated.Objective: To discuss the management of HCV-infected IBD patients, focusing our attention on the timing of DAAs administration subjects needing biologics.Methods: Relevant articles addressing HCV management in patients needing biologics were identified by searching from PubMed, MEDLINE and Scopus.Results: Three possible timing strategies were identified: (1) sequential strategy, meaning the choice of treating firstly the active IBD with biologics and then, once the acute phase has been controlled, treating the HCV infection; (2) concomitant strategy, that is the contemporaneous beginning of DAAs and biologics administration; (3) inverted sequential strategy—the administration of antiviral therapy before biologics in HCV-infected IBD patients. The potential pharmacological interactions between biologics and DAAs have also been reported.Conclusions: Clinical management of HCV-infected IBD patients remains a challenging problem for clinicians, especially in terms of timing choice. Recent published data about DAAs are very encouraging also in IBD patients. All strategies could be considered safe and effective. However, further data are immediately required in order to evaluate hepatic toxicity of novel immunosuppressive drugs in IBD.

Pharmacokinetic-pharmacodynamic influence of N-palmitoylethanolamine, arachidonyl-2′-chloroethylamide and WIN 55,212-2 on the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice

We evaluated the effects of ACEA (selective cannabinoid (CB)1 receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB1 and CB2 receptor agonist) and N-palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy. PEA, ACEA or WIN intraperitoneal (i.p.) administration decreased the severity of tonic-clonic seizures. We also studied the effects of PEA, WIN or ACEA after co-administration with NIDA-41020 (CB1 receptor antagonist) or GW6471 (PPAR-α antagonist) and compared the effects of WIN, ACEA and PEA in order to clarify their mechanisms of action. PEA has anticonvulsant features in DBA/2 mice mainly through PPAR-α and likely indirectly on CB1 receptors, whereas ACEA and WIN act through CB1 receptors. The co-administration of ineffective doses of ACEA, PEA and WIN with some antiepileptic drugs (AEDs) was examined in order to identify potential pharmacological interactions in DBA/2 mice. We found that PEA, ACEA and WIN co-administration potentiated the efficacy of carbamazepine, diazepam, felbamate, gabapentin, phenobarbital, topiramate and valproate and PEA only also that of oxcarbazepine and lamotrigine whereas, their co-administration with levetiracetam and phenytoin did not have effects. PEA, ACEA or WIN administration did not significantly influence the total plasma and brain levels of AEDs; therefore, it can be concluded that the observed potentiation was only of pharmacodynamic nature. In conclusion, PEA, ACEA and WIN show anticonvulsant effects in DBA/2 mice and potentiate the effects several AEDs suggesting a possible therapeutic relevance of these drugs and their mechanisms of action.

Cannabidivarin‐rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor‐independent mechanism

Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. The anticonvulsant profiles of two CBDV BDSs (50-422 mg·kg(-1) ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays. CBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg(-1) ) and audiogenic seizure models (≥87 mg·kg(-1) ), and suppressed pilocarpine-induced convulsions (≥100 mg·kg(-1) ). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co-administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ(9) -tetrahydrocannabinol and Δ(9) -tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV. CBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.

2739 – Drug interactions in a regional secure unit

Polypharmacy continues to be a major concern in psychiatry. Besides the risk of unintended and untoward pharmacological interactions, it carries the potential to cause prescriber liability and increased healthcare costs. Although polypharmacy has been commonly reported in forensic units, there have been no studies examining potentially serious pharmacological interactions in secure settings. To identify the prevalence of potential pharmacological interactions through a cross-sectional study of prescribing patterns in a medium secure unit in the UK. Medications prescribed for all 43 patients on 3 male medium secure wards in London in September 2012 were analyzed for potential pharmacological interactions using the Medscape Drug Database/Interaction checker. A total of 233 regular and 113 ‘as required (p.r.n)’ medications were prescribed. 98 medications were psychotropic and 248 were physical health related. 284 potential pharmacological interactions were present with an average of 6.6 interactions per patient (1-28), involving 31 of the 43 patients(72.09%). These interactions were categorized into four groups: 1.Contraindicated (4.65% of patients;2 interactions) 2.Serious-Use Alternative(30.23% patients;20 interactions) 3.Significant- Monitor Closely(69.6% patients; 232 interactions) and 4.Minor(39.53% patients;30 interactions). Interestingly, 65% of contraindicated/serious interactions involved non-psychotropic medication. The findings highlight the high prevalence of potential pharmacological interactions in the forensic population. The challenging presentations in forensic psychiatry often necessitate ‘p.r.n. prescribing’ and medication augmentation to treat partial response. However, this can lead to unpredictable and dangerous interactions. Clinicians should be mindful of the pharmacodynamic and pharmacokinetic implications prior to prescribing psychotropic and non-psychotropic drugs.

Gender differences, polypharmacy, and potential pharmacological interactions in the elderly

OBJECTIVE:This study aims to analyze pharmacological interactions among drugs taken by elderly patients and their age and gender differences in a population from Porto Alegre, Brazil.METHODS:We retrospectively analyzed the database provided by the Institute of Geriatric and Gerontology, Porto Alegre, Brazil. The database was composed of 438 elderly and includes information about the patients' disease, therapy regimens, utilized drugs. All drugs reported by the elderly patients were classified using the Anatomical Therapeutic and Chemical Classification System. The drug-drug interactions and their severity were assessed using the Micromedex® Healthcare Series.RESULTS:Of the 438 elderly patients in the data base, 376 (85.8%) used pharmacotherapy, 274 were female, and 90.4% of females used drugs. The average number of drugs used by each individual younger than 80 years was 3.2±2.6. Women younger than 80 years old used more drugs than men in the same age group whereas men older than 80 years increased their use of drugs in relation to other age groups. Therefore, 32.6% of men and 49.2% of women described at least one interaction, and 8.1% of men and 10.6% of women described four or more potential drug-drug interactions. Two-thirds of drug-drug interactions were moderate in both genders, and most of them involved angiotensin-converting enzyme inhibitor, non-steroidal anti-inflammatory, loop and thiazide diuretics, and β-blockers.CONCLUSION:Elderly patients should be closely monitored, based on drug class, gender, age group and nutritional status.

Use of antineoplastic agents in patients with cancer who have HIV/AIDS

Highly active antiretroviral therapy (HAART) has substantially reduced morbidity and mortality of AIDS-related complications in patients with HIV; however, the prevalence of AIDS-defining cancers and non-AIDS-defining cancers has increased. In this Review we discuss the management of HAART pharmacotherapy in relation to cytotoxic chemotherapy or targeted antineoplastic agents. We will review potential pharmacological interactions between antiretroviral and antineoplastic therapies and consider how to combine antiretroviral and antineoplastic agents in patients with HIV who are receiving HAART therapy.

Old-age inflammatory bowel disease onset: A different problem?

Inflammatory bowel disease (IBD) in patients aged > 60 accounts for 10%-15% of cases of the disease. Diganostic methods are the same as for other age groups. Care has to be taken to distinguish an IBD colitis from other forms of colitis that can mimick clinically, endoscopically and even histologically the IBD entity. The clinical pattern in ulcerative colitis (UC) is proctitis and left-sided UC, while granulomatous colitis with an inflammatory pattern is more common in Crohn's disease (CD). The treatment options are those used in younger patients, but a series of considerations related to potential pharmacological interactions and side effects of the drugs must be taken into account. The safety profile of conventional immunomodulators and biological therapy is acceptable but more data are required on the safety of use of these drugs in the elderly population. Biological therapy has risen question on the possibility of increased side effects, however this needs to be confirmed. Adherence to performing all the test prior to biologic treatment administration is very important. The overall response to treatment is similar in the different patient age groups but elderly patients have fewer recurrences. The number of hospitalizations in patients > 65 years is greater than in younger group, accounting for 25% of all admissions for IBD. Mortality is similar in UC and slightly higher in CD, but significantly increased in hospitalized patients. Failure of medical treatment continues to be the most common indication for surgery in patients aged > 60 years. Age is not considered a contraindication for performing restorative proctocolectomy with an ileal pouch-anal anastomosis. However, incontinence evaluation should be taken into account an individualized options should be considered.

Combinations of Cocaine with Other Dopamine Uptake Inhibitors: Assessment of Additivity

Drugs that inhibit dopamine (DA) reuptake through actions at the dopamine transporter (DAT) have been proposed as candidates for development as pharmacotherapies for cocaine abuse. Accordingly, it is important to understand the potential pharmacological interactions of cocaine with other drugs acting at the DAT. Effects of combinations of cocaine with a cocaine analog, 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (WIN 35,428), were compared quantitatively with the combinations of cocaine with the N-butyl,4',4''-diF benztropine analog, 3-(bis(4-fluorophenyl)methoxy)-8-butyl-8-azabicyclo[3.2.1]octane (JHW 007), to determine whether their effects on DA levels in the shell of the nucleus accumbens (NAC) in mice differed. Each of the drugs alone produced dose-related elevations in NAC DA levels. In contrast to the other drugs, JHW 007 was less effective, producing maximal effects that approached 400% of control versus approximately 700% with the other drugs. In addition, the JHW 007 dose-effect curve was not as steep as those for cocaine and WIN 35,428. Combinations of cocaine with its analog, WIN 35,428, were most often greater than those predicted based on dose additivity. In contrast, combinations of cocaine with JHW 007 were most often subadditive. This outcome is consistent with recent studies suggesting that structurally divergent DA uptake inhibitors bind to different domains of the DAT, which can result in different DAT conformations. The conformational changes occurring with JHW 007 binding may result in functional outcomes that alter its abuse liability and its effects in combination with cocaine.

Systematic review: does concurrent therapy with 5‐ASA and immunomodulators in inflammatory bowel disease improve outcomes?

With greater use of immunomodulators in inflammatory bowel disease (IBD), it is uncertain whether concurrent therapy with both 5-aminosalicylic acid [5-ASA, mesalazine (mesalamine)] and an immunomodulator is necessary. To determine whether concurrent therapy with both 5-ASA and immunomodulator(s) improves outcomes in IBD. Systematic review with search terms 'azathioprine, 6-mercaptopurine, thiopurine(s), 5 aminosalicylic acid, mesalazine, inflammatory bowel disease, ulcerative colitis, Crohn's disease, immunosuppressant(s), immunomodulator and methotrexate' in November 2007 to identify clinical trials on concurrent 5-ASA and immunomodulator therapy. Two small controlled studies were found. Neither showed a benefit on disease control beyond immunomodulator monotherapy. Potential pharmacological interactions exist between 5-ASA and thiopurines. Whilst circumstantial, epidemiological and laboratory evidence suggests that 5-ASA may assist colorectal cancer (CRC) chemoprevention, it may simply be via anti-inflammatory effects. With changes in practice, ethical issues and the long lead-time needed to demonstrate or disprove an effect, no clinical studies can/will directly answer this. The costs of avoiding one CRC in IBD may be as low as 153 times the annual cost of 5-ASA therapy. It is unclear whether concurrent 5-ASA and immunomodulator therapy improves outcomes of disease control, drug toxicity or compliance. Concurrent therapy of 5-ASA and immunomodulators may decrease CRC risk at 'acceptable' cost.

Estudio epidemiológico sobre la enfermedad ácido-péptica en pacientes ancianos ambulatorios

Background the main objectives of this study were to determine the prevalence of peptic acid disease (PAD) in elderly outpatients and to identify the profile and characteristics of these patients. We also assessed comorbidity and polypharmacy use (specifically, the use of drugs with potential pharmacological interactions), with special emphasis on nonsteroidal antiinflammatory drugs (NSAIDs) and gastroprotective drugs. Material and methods we performed a cross-sectional, observational, multicenter study of elderly patients attending 15 geriatric outpatient clinics (80 consecutive patients aged more than 65 years old per center). Data on demographic factors, associated diseases, and drug consumption (NSAIDS and antisecretory therapy) were collected. Results a total of 1119 patients were included in the study. The mean age was 80 years old (SD 6.7) and 65% of the participants were women. The prevalence of PAD was 41%. The most common PAD was gastroesophageal reflux disease (GERD) (23%), with a wide variety of symptoms. Comorbidity was high, with more than 90% of the patients suffering from two or more diseases. The mean number of concomitant drugs was 4, and 422 patients (37.8% of the sample) were taking antisecretory drugs. The use of NSAIDs was common (15%), and only one-third of these patients received gastroprotective therapy with proton pump inhibitors (PPIs). Conclusions PAD is highly prevalent in elderly outpatients. The most frequent diagnosis is GERD. In this population comorbidity and polypharmacy use were high, which could lead to a high percentage of pharmacological interactions. Effective gastroprotective therapy with a PPI in the subgroup of elderly outpatients taking NSAIDs was low.