Biomedical subjects

Elisabetta Poluzzi

Publications and source records attributed to Elisabetta Poluzzi.

12 recordsLinked to original sources

PubMed2006

Adherence to chronic cardiovascular therapies: persistence over the years and dose coverage.

AIM: To evaluate adherence to chronic cardiovascular drug treatments, in terms of long-term persistence and dose coverage. METHODS: General practice prescription data of antihypertensives, lipid-lowering agents, oral hypoglycaemic agents and nitrates were collected over a 5-year period (1998-2002) in a Northern Italian district (Ravenna, 350,000 inhabitants). We selected subjects (>40 years) receiving at least one prescription of the above drugs in December 1999. For each patient, we documented the regimen at the time of selection and evaluated adherence to treatment during the following 3 years in terms of persistence (at least one prescription per year) and daily coverage (recipients of an amount of medication consistent with daily treatment). RESULTS: Fewer than 10% of the 32 068 selected subjects were naive to treatment. Antihypertensives were the most represented therapeutic category. Among patients already on treatment in December 1999, persistence was virtually complete, whereas >40% of naive patients withdrew within 1 year, except for nitrates. The rates of coverage were always much lower than the corresponding values of persistence. Coverage was significantly higher in older patients (chi(2) for trend 69.41; P < 0.001), males (odds ratio 1.30; 95% confidence interval 1.25, 1.36) and users receiving more than one therapeutic category. CONCLUSIONS: Lack of adherence to chronic cardiovascular treatments represents an important matter of concern: although most people continued treatment over the years, less than 50% received an amount of drugs consistent with daily treatment, thus jeopardizing the proved beneficial effects of available medications.

Adult↗

PubMed2006

An update on the first decade of the European centralized procedure: how many innovative drugs?

AIMS: In a previous paper, we proposed an algorithm to assess the degree of therapeutic innovation of the agents approved by the European centralized procedure, which must be followed by biotechnological products and is optional for drugs claimed as innovative. A low overall degree of therapeutic innovation (about 30%) was found. This figure may be an underestimate of the actual level of innovation, because common biotechnological products, such as recombinant human insulins, must follow this procedure. To test the hypothesis that therapeutic innovation prevails among nonbiotechnological products, we evaluated separately the degree of therapeutic innovation of biotechnological vs. nonbiotechnological agents in the first decade of European Medicines Agency activity, also studying a possible time trend. METHODS: We assessed, for each drug: (i) the seriousness of the target disease, (ii) the availability of previous treatments, and (iii) the extent of therapeutic effect according to the previously proposed algorithm. RESULTS: Our analysis considered 251 medicinal products corresponding to 198 active substances, classified according to four main areas as therapeutic agents (88.9%), diagnostics (5.5%), vaccines (5.1%) and life-style drugs (0.5%). Among all therapeutic agents, 49 out of 176 agents (28%) were classified as having an important degree of therapeutic innovation. Fifteen out of 60 biotechnological therapeutic agents were considered important therapeutic innovations (25%), whereas this figure was 29% for nonbiotechnological agents. CONCLUSIONS: Among active substances claimed as innovative by the manufacturers, only a minority deserve this definition according to our algorithm.

Drug Approval↗

PubMed2006

Gastro-intestinal problems and concomitant medication in NSAID users: additional findings from a questionnaire-based survey in Italy.

BACKGROUND: In a previous questionnaire-based survey, we found extensive use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with risk factors for serious gastrointestinal complications. AIM: This study focused on the use of NSAIDs in subjects who reported either (a) pre-existing disorders which would have required caution in using NSAIDs (e.g. dyspepsia/heartburn or peptic ulcer) or (b) co-medication with drugs having a high risk of interacting with NSAIDs. METHODS: Between March and September 2002, 65 general practitioners (GPs) submitted a validated self-administered questionnaire on health status and drug use to 3,250 subjects (age >or=18 years, stratified by sex and age). The questionnaire was divided into three parts: (1) sociodemographic information, (2) symptoms/illnesses (in the previous 6 months) and (3) drugs taken during the previous week. RESULTS: Of the 2,738 subjects who filled in the questionnaire (84% of responders), 633 (23%) used NSAIDs and, among them, 114 (18%) were chronic users. Among the subjects reporting dyspepsia/heartburn or ulcer (n=909 of 2,738), 24% were occasional NSAID users and 6% chronic users. Of the chronic NSAID users reporting gastrointestinal symptoms, 35% also used a drug for acid-related disorders, but only 14% used daily a proton pump inhibitor (PPI). One hundred six subjects used concomitantly more than one NSAID. Eighteen percent of the subjects using corticosteroids also reported NSAID use; similar proportions were seen in subjects using selective serotonin reuptake inhibitor (SSRI) antidepressants or calcium channel blockers, whereas 6% of the subjects with oral anticoagulants used NSAIDs. CONCLUSIONS: Our study shows that NSAIDs are frequently used in patients with upper gastrointestinal complaints or in combination with potentially interacting medications. Adverse effects and untoward drug interactions should be monitored in patients treated with NSAIDs in order to minimise their occurrence.

Adult↗

PubMed2005

Initial treatment of hypertension and adherence to therapy in general practice in Italy.

BACKGROUND: Antihypertensive agents are among the most used therapeutic classes. The approach to the pharmacological treatment of hypertension is guided by international recommendations and adherence to treatment is known to result in effective prevention of cardiovascular risk. AIM: The aim of this study was to evaluate the pattern of use of antihypertensive agents in general practice in terms of drug choice for the initial treatment of hypertension and adherence to treatments among newly recruited patients. METHODS: We collected the data of all antihypertensive drugs prescribed by general practitioners (GPs) and reimbursed between January 1998 and December 2002 by a Local Health Authority of Emilia Romagna (Ravenna district, 350,000 inhabitants). We selected subjects aged 40 years and older, permanently living in the area during the whole period of the study, who received their first prescription of antihypertensives between January and December 1999, with no prescription of antihypertensive agents in the previous year. For each patient, we documented the starting regimen and evaluated adherence to treatment in terms of persistence during the years (patients were defined persistent if they received at least one prescription per year) and in terms of daily coverage (patients were defined covered if they received an amount of drugs consistent with a daily treatment). Finally, switches or addition of other therapeutic classes during the 3-year period were identified. RESULTS: A cohort of 6,043 subjects receiving their first antihypertensive treatment in 1999 was obtained. Regarding the starting regimen, monotherapies with angiotensin converting enzyme inhibitors (n = 1,597; 26%) or calcium channel blockers (n = 1126; 19%) were the most frequently prescribed. Of the patients, 21% started with a drug combination regimen. Regarding adherence to treatment, 18% of the cohort received only one prescription throughout the 3 years, 13% received more than one prescription but stopped the therapy during the first year, 69% were persistent during the second year and 60% also during the third year. Only 34% were covered during the first year and 24% also during the second year, whereas only 20% of the patients resulted covered throughout the 3 years. Among persistent patients, 41% maintained the same antihypertensive regimen throughout the 3 years, 25% added other drugs to the initial treatment and 34% switched to completely different regimens. CONCLUSIONS: Our findings reflect the lack of convergence among guidelines on the drug class(es) to be considered as first choice in the initial treatment of hypertension. Although an intervention in this field may have important implications in terms of cost savings, the ongoing debate does not allow us to draw definite conclusions on whether measures should be taken by the National Health Authority. However, the lack of adherence to antihypertensive treatment is undoubtedly a matter of concern for public health and should be addressed with appropriate interventions.

Adult↗

PubMed2005

QT prolongation through hERG K(+) channel blockade: current knowledge and strategies for the early prediction during drug development.

Prolongation of the QT interval of the electrocardiogram is a typical effect of Class III antiarrhythmic drugs, achieved through blockade of potassium channels. In the past decade, evidence has accrued that several classes of drugs used for non-cardiovascular indications may prolong the QT interval with the same mechanism (namely, human ether-a-go-go-related gene (hERG) K(+) channel blockade). The great interest in QT prolongation is because of several reasons. First, drug-induced QT prolongation increases the likelihood of a polymorphous ventricular arrhythmia (namely, torsades de pointes, TdP), which may cause syncope and degenerate into ventricular fibrillation and sudden death. Second, the fact that several classes of drugs, such as antihistamines, fluoroquinolones, macrolides, and neuroleptics may cause the long QT syndrome (LQTS) raises the question whether this is a class effect (e.g., shared by all agents of a given pharmacological class) or a specific effect of single agents within a class. There is now consensus that, in most cases, only a few agents within a therapeutic class share the ability to significantly affect hERG K(+) channels. These compounds should be identified as early as possible during drug development. Third, QT prolongation and interaction with hERG K(+) channels have become surrogate markers of cardiotoxicity and have received increasing regulatory attention. This review briefly outlines the mechanisms leading to QT prolongation and the different strategies that can be followed to predict this unwanted effect. In particular, it will focus on the approaches recently proposed for the in silico screening of new compounds.

Animals↗

PubMed2005

Idiopathic Dyspepsia.

Idiopathic dyspepsia refers to pain and/or discomfort perceived in the epigastrium that is not secondary to organic, systemic, or metabolic diseases. Symptoms may overlap with those of gastroesophageal reflux disease and irritable bowel syndrome. Gastrointestinal motor disorders, hypersensitivity to mechanical or chemical stimuli, and psychosocial factors can act individually or in concert to induce the symptoms of dyspepsia. Accordingly, there is no single therapy, and treatment must be individualized. Eradication of Helicobacter pylori infection rarely achieves symptom improvement. Treatment of idiopathic dyspepsia should begin by reassuring the patient about the benign nature of the syndrome and educating them on the knowledge that has been achieved in recent years regarding potential causes of the syndrome. Both prokinetic and antisecretory drugs have been reported to improve dyspeptic symptoms, but results are not completely convincing. Although well-designed studies demonstrate superiority of proton pump inhibitors over placebo, it should be noted that patients with nonerosive gastroesophageal reflux disease were invariably included; when these patients are excluded, the benefit of antisecretory medications is questionable. We suggest that patients with idiopathic dyspepsia be initially treated according to the predominant symptom. Those with epigastric pain/burning should receive a trial with standard doses of proton pump inhibitors for 4 to 8 weeks, whereas prokinetic patients should be prescribed at recommended doses for similar periods of time to patients with nonpainful dyspeptic symptoms such as posprandial fullness, early satiety, nausea, or vomiting. Nonresponders may benefit from combination therapies or short trials with higher doses of drugs. Visceral analgesics and antidepressants can also be prescribed alone or in combinations with other therapeutic strategies. Recent studies demonstrate utility for psychologic therapy and hypnotherapy, although truly controlled studies are difficult in this area. Herbal medicines deserve further evaluation.

Journal Article↗

PubMed2004

Pattern of NSAID use in the Italian general population: a questionnaire-based survey.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medicines in the developed countries. The most important adverse reactions involve the upper gastrointestinal tract and can be life threatening. A detailed knowledge of the pattern of use of NSAIDs may help doctors in advising their patients about appropriateness and safety of use. AIM: The aim of the present survey was to evaluate the prevalence and pattern of NSAID use in the general population, as well as the main characteristics of NSAID users. METHODS: Between March and September 2002, a self-administered questionnaire was submitted to a random sample, stratified by gender and age, representative of the Italian adult population (n=3,250). The questionnaire was divided into three parts regarding: (1) sociodemographic information, (2) symptoms/illnesses and (3) any drug taken during the previous week and the corresponding purpose. A statistical analysis (logistic regression) was performed. RESULTS: Of the 2,738 subjects who filled in the questionnaire, 65% took at least one drug in the previous week and, among them, 35% used NSAIDs (top drug class; n=633). Of the NSAID users, 20% were >/=65 years of age and 18% were chronic users (daily or frequent use for more than 6 months). NSAID use was significantly higher in women, both for overall and chronic use. The older age groups showed an increasing risk of chronic NSAID use. Among NSAIDs, nimesulide was the most used compound (35%) followed by acetylsalicylic acid (14%) and ibuprofen (11%). The main reasons for NSAID use, as reported by subjects, were: headache (25%), osteoarticular pain (19%), unspecified pain (15%) and osteoarthrosis (9%). More than 50% of all the NSAIDs were prescribed by physicians (general practitioner, specialist, hospital physician), whereas about 44% were taken as self-treatment or following the advice of a pharmacist, relative/friend, etc. CONCLUSIONS: Our study confirms that NSAIDs are widely used in the Italian general population and that, in most cases, they are used in accordance with their approved indications. However, their large and often chronic use in the elderly, as well as the high frequency of self-treatment, recommends a higher awareness by all physicians.

Adult↗

PubMed2004

Antibacterial macrolides: a drug class with a complex pharmacological profile.

Macrolides are widely used antibacterial agents. Although generally well tolerated, they have a number of important additional pharmacological effects, which can sometimes result in significant adverse reactions. This review focuses on three of these side effects: the prokinetic action associated with stimulation of motilin receptors, the proarrhythmic effect due to prolongation of the QT interval of the electrocardiogram and the potential for drug interactions due to inhibition of drug metabolising enzymes. For macrolides that have obtained marketing authorisation in Italy, United Kingdom or United States of America, we also considered whether these actions are properly reported in the approved summaries of the product characteristics and tried to provide strategies to identify patients at risk of significant side effects when macrolides are administered.

Animals↗

PubMed2003

Prescriptions of antidepressants in primary care in Italy: pattern of use after admission of selective serotonin reuptake inhibitors for reimbursement.

BACKGROUND: Italy is reported to have a relatively low consumption of antidepressants. This is probably due to the fact that until 2000 antidepressants were reimbursed with some restrictions. AIM: To describe the pattern of use of antidepressants in primary care in Italy, after admission of selective serotonin reuptake inhibitors (SSRIs) for reimbursement without restrictions. METHODS: We collected prescription data of antidepressants (ATC code: N06) reimbursed between January 1999 and March 2002 from three local health authorities in Emilia Romagna. Then, we calculated the prevalence of use for the different therapeutic classes of antidepressants, by age and gender. Moreover, after selecting a cohort of incident adult patients to follow for 6 months after the first prescription, we analysed the continuity, the average daily doses and the average duration of treatment. RESULTS: Out of 1000 subjects, 78 received at least one prescription of antidepressants in 1 year. The prevalence of use increased with age from 43 to 136/1000. Women used antidepressants more frequently than men, with a ratio varying from 1.6 to 2, depending on age. SSRIs were the most used drugs (63%), and their prevalence of use diminished with age; on the contrary, use of mianserine and trazodone increased with age, and that of the other antidepressants did not vary. About 60% of the subjects received occasional prescriptions. Continuous treatment was more frequent with SSRIs and in subjects older than 34 years. Daily doses were higher in patients receiving newer drugs (0.9-1 DDD per day), and lower in patients receiving the older agents (0.3-0.4 DDD per day). The average daily doses were usually lower than those recommended for the treatment of the major depression, especially for tricyclics, trazodone and reboxetine. Overall, doses were within the recommended range in about 75% of recipients of newer antidepressants (i.e., SSRIs, venlafaxine, mirtazapine and reboxetine), and in less than 30% of recipients of older drugs (i.e., tricyclics, trazodone and mianserine). In 59% of subjects receiving continuous treatment, the duration of the therapeutic course was at least 6 months. CONCLUSIONS: We found a high prevalence of use of antidepressants in primary care with a frequency of occasional use higher than in other countries. Only rarely were doses and duration of treatment consistent with recommendations for treatment of depression. Recipients of newer drugs received doses consistent with a use for major depression more frequently than others; however, rates of 6 month duration did not differ among drug classes.

Adult↗

PubMed2002

Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers.

In this paper, we present a pharmacophore for QT-prolonging drugs, along with a 3D QSAR (CoMFA) study for a series of very structurally variegate HERG K(+) channel blockers. The blockade of HERG K(+) channels is one of the most important molecular mechanisms through which QT-prolonging drugs increase cardiac action potential duration. Since QT prolongation is one of the most undesirable side effects of drugs, we first tried to identify the minimum set of molecular features responsible for this action and then we attempted to develop a quantitative model correlating the 3D stereoelectronic characteristics of the molecules with their HERG blocking potency. Having considered an initial set of 31 QT-prolonging drugs for which the HERG K(+) channel blocking activity was measured on mammalian transfected cells, we started the construction of a theoretical screening tool able to predict whether a new molecule can interact with the HERG channel and eventually induce the long QT syndrome. This in silico tool might be useful in the design of new drug candidates devoid of the physicochemical features likely to cause the above-mentioned side effect.

Anti-Arrhythmia Agents↗

PubMed2002

Non-antiarrhythmic drugs prolonging the QT interval: considerable use in seven countries.

AIMS: Many drugs belonging to different therapeutic classes appear to share a potentially fatal side-effect: ventricular tachyarrhythmias associated with QT prolongation. The aim of this study was to assess the relevance and the magnitude of the problem in seven countries by grouping all nonantiarrhythmic drugs according to the type of evidence on QT prolongation and analysing their sales data. METHODS: We divided all nonantiarrhythmic QT-prolonging agents into the following categories (in increasing order of clinical relevance): group A, drugs with published clinical or preclinical evidence on QT prolongation or with relevant official warnings; group B, drugs with published clinical or preclinical evidence; group C, drugs with published clinical evidence; group D, drug with published clinical evidence on torsades de pointes or ventricular arrhythmias associated with QT prolongation; group E, drugs belonging to group D with official warnings. We retrieved 1998 sales data from community pharmacies in seven countries (Australia, Denmark, England, Germany, Greece, Italy and Sweden). Data for individual agents were expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). Overall use in each country was calculated for each drug group. Groups D and E were considered as the most clinically relevant. RESULTS: Among the 102 nonantiarrhythmic agents meeting at least one of the inclusion criteria, 33 drugs had sales data > or =1 DDD/1000/day and 71 drugs had a use > or =0.1 DDD/1000/day in at least one country. Among the 37 nonantiarrhythmic agents with published reports of ventricular arrhythmias associated with QT prolongation, 12 compounds had sales data > or =1 DDD/1000/day. Total consumption in each country ranged: from 51.9 to 94.7 DDD/1000/day for group A; from 51.6 to 92.7 DDD/1000/day for group B; from 37.1 to 76.6 DDD/1000/day for group C; from 12.9 to 29.1 DDD/1000/day for group D; and from 5.8 to 15.3 DDD/1000/day for group E. CONCLUSIONS: In spite of wide variations in the sales of individual agents, the overall extent of use of nonantiarrhythmic QT-prolonging drugs was of the same order of magnitude in all countries. The significant use of drugs belonging to categories D and E should prompt careful risk/benefit assessment of each agent.

Australia↗

PubMed2002

Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview.

The long and growing list of non-antiarrhythmic drugs associated with prolongation of the QT interval of the electrocardiogram has generated concern not only for regulatory interventions leading to drug withdrawal, but also for the unjustified view that QT prolongation is usually an intrinsic effect of a whole therapeutic class [e.g. histamine H(1) receptor antagonists (antihistamines)], whereas, in many cases, it is displayed only by some compounds within a given class of non-antiarrhythmic drugs because of an effect on cardiac repolarisation. We provide an overview of the different classes of non-antiarrhythmic drugs reported to prolong the QT interval (e.g. antihistamines, antipsychotics, antidepressants and macrolides) and discusses the clinical relevance of the QT prolonging effect. Drug-induced torsade de pointes are sometimes considered idiosyncratic, totally unpredictable adverse drug reactions, whereas a number of risk factors for their occurrence is now recognised. Widespread knowledge of these risk factors and implementation of a comprehensive list of QT prolonging drugs becomes an important issue. Risk factors include congenital long QT syndrome, clinically significant bradycardia or heart disease, electrolyte imbalance (especially hypokalaemia, hypomagnesaemia, hypocalcaemia), impaired hepatic/renal function, concomitant treatment with other drugs with known potential for pharmacokinetic/pharmacodynamic interactions (e.g. azole antifungals, macrolide antibacterials and class I or III antiarrhythmic agents). This review provides insight into the strategies that should be followed during a drug development program when a drug is suspected to affect the QT interval. The factors limiting the predictive value of preclinical and clinical studies are also outlined. The sensitivity of preclinical tests (i.e. their ability to label as positive those drugs with a real risk of inducing QT pronglation in humans) is sufficiently good, but their specificity (i.e. their ability to label as negative those drugs carrying no risk) is not well established. Verapamil is a notable example of a false positive: it blocks human ether-a-go-go-related (HERG) K(+) channels, but is reported to have little potential to trigger torsade de pointes. Although inhibition of HERG K(+) channels has been proposed as a primary test for screening purposes, it is important to remember that several ion currents are involved in the generation of the cardiac potential and that metabolites must be specifically tested in this in vitro test. At the present state of knowledge, no preclinical model has an absolute predictive value or can be considered as a gold standard. Therefore, the use of several models facilitates decision making and is recommended by most experts in the field.

Anti-Bacterial Agents↗