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PubMed2005

Pharmacological and clinical aspects of antiepileptic drug use in the elderly.

In this article, epidemiological and clinical aspects related to the use of antiepileptic drugs (AEDs) in the elderly are highlighted. Studies have shown that people with epilepsy receiving AED treatment show important deficits in physical and social functioning compared with age-matched people without epilepsy. To what extent these deficits can be ascribed to epilepsy per se or to the consequences of AED treatment remains to be clarified. The importance of characterizing the effects of AEDs in an elderly population is highlighted by epidemiological surveys indicating that the prevalence of AED use is increased in elderly people, particularly in those living in nursing homes. Both the pharmacokinetics and the pharmacodynamics of AEDs may be altered in old age, which may contribute to the observation that AEDs are among the drug classes most commonly implicated as causing adverse drug reactions in an aged population. Age alone is one of several contributors to alterations in AED response in the elderly; other factors include physical frailty, co-morbidities, dietary influences, and drug interactions. Individualization of dosage, avoidance of unnecessary polypharmacy, and careful observation of clinical response are essential for an effective and safe utilization of AEDs in an elderly population.

Aged↗

PubMed2006

Diagramming patients' views of root causes of adverse drug events in ambulatory care: an online tool for planning education and research.

OBJECTIVE: Diagram patients' views of the causes of adverse drug events (ADEs) in ambulatory care, examine characteristics of causes reported by patients, and identify those that have been studied in the medical and social science literatures. METHODS: Twenty-two primary care patients were interviewed using a root cause analysis approach. Diagrams derived from interviews were consolidated and displayed online as a composite interactive causal diagram. Patient-reported causes were compared to evidence in the social science and medical literatures. RESULTS: Patients ascribed 164 causes to ADEs occurring through eight major pathways, including medication nonadherence, prescriber-patient miscommunication, patient medication error, failure to read medication label/insert, polypharmacy, patient characteristics, pharmacist-patient miscommunication, and self medication. Most frequently reported causes were intrapsychic and interpersonal in nature. Most patient-reported causes have been studied, however, several practical and motivational antecedents lack research. CONCLUSION: Conducting root cause analysis with patients reveals multiple logically linked aspects of medication safety in community settings that merit further research and consideration in patient and prescriber education. PRACTICE IMPLICATIONS: This causal diagram provides a broadly accessible planning tool for reducing ambulatory ADEs by showing a comprehensive picture of potential causes, identifying causal factors supported by evidence, and disclosing likely consequences of change efforts. Also, patient-centered medication safety strategies should address psychological and practical barriers patients face in their everyday lives.

Adolescent↗

PubMed2001

Optimizing the use of beta-blockers in the effective treatment and management of heart failure: a case study approach.

Today, heart failure is an increasing concern in the United States. Its prognoses are poor and its treatment is a complicated endeavor, because heart failure is not a single disease state. Rather, it is a syndrome with a cyclic pathophysiology composed of multiple mechanisms. Effective case management of heart failure must address each of the many changes involved in this syndrome, and therapy must be individualized, especially because patients with heart failure often require regimens of five or more drugs. In special populations, such as the elderly and/or patients with concomitant diseases requiring added medication, polypharmacy becomes an important issue. Maintaining consistent compliance with the treatment regimen and patient education regarding symptoms of fluid retention can be critical. Currently, beta-blockers, in addition to standard therapy, are recommended as first-line treatment in mild-to-moderate heart failure. The three cases presented in this article illustrate some common scenarios encountered and clinical decisions made when beta-blockers are used in the management of heart failure.

Adrenergic beta-Antagonists↗

PubMed2003

Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2 study.

We recently published the results of the Steno-2 study, which evaluated the benefits of intensified integrated behavior modification and targeted polypharmacy. The results provide abundant evidence that an ambitious treatment strategy is superior to a conventional one. The study involved 160 high-risk type 2 diabetic patients with microalbuminuria-a strong risk factor of both macrovascular and microvascular complications-aged 55.1 years, who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years. In the intensive group, a stepwise treatment plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors. The conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals. The specific significant group differences in the degree of change in key clinical and biochemical variables at the end of the study were (in the intensive group): lower systolic and diastolic blood pressures, hemoglobin A(1c) (HbA(1c)), fasting serum total and low-density lipoprotein (LDL) cholesterol, fasting serum triglycerides, and 24-hour urine albumin excretion, as well as increased carbohydrate and decreased fat intake as percentage of total energy. There was no difference in weight gain between groups during follow-up and no other major side effects were reported. The primary end point was a macrovascular outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis. The differences between groups in surrogate end points translated into the following significant group differences in final clinical end points: 44% of patients in the conventional group had a cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50%. Also, the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group. In conclusion, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy, by about half. The challenge is to ensure that this experience is widely adopted in daily practice.

Behavior Therapy↗

PubMed1998

Neuropharmacology in the elderly.

Psychotropic medications present special problems in the elderly because of altered pharmacokinetics and pharmacodynamics. Aging is associated with changes in absorption, distribution, and elimination of medications. Pharmacodynamic changes refer to alterations in end-organ responsiveness occurring with aging. Common problems that further complicate psychotropic drug use in the elderly include polypharmacy, compliance, lack of specific diagnosis, and concomitant physical illness. The treating physician must be aware of these issues when prescribing psychotropic medications for the elderly.

Aged↗

PubMed2000

Reported current use of prescription drugs and some of its determinants among 35 to 65-year-old women in mid-Sweden: A population-based study.

To investigate prescribed drug utilization in a middle-aged female population and factors possibly related to drug consumption in this population. A random sample of 4200 women aged 35-65 years, drawn from the population register of seven countries in mid-Sweden, received a postal questionnaire. Two thousand nine hundred ninety one (2991) (71.2%) women responded. Forty percent (40%) of the women were currently using drugs and 12% of the users were taking four drugs or more. Polypharmacy increased by age. A large number of factors were correlated with current drug use. In multivariate analyses age, perceived health, body mass index, and educational level remained significantly related to drug use, while factors such as menopausal state, smoking habits, employment status, marital status, and physical activity lost their significance. Current drug use among women increased by age, bad perceived health status, obesity, and college or university education.

Adult↗

PubMed1998

A follow-up study of adults with learning disabilities and epilepsy.

A programme to review the drug treatment of 215 adults with epilepsy and learning disabilities occurred in Leicestershire between 1982 and 1985. In 1997, a Leicestershire-wide study of epilepsy suffered by adults with learning disabilities was undertaken. The study sought information about many aspects of the epilepsy including the prescribing of medicines. One hundred and thirty-eight adults were common to both studies. A greater proportion was suffering active epilepsy in 1997 than in 1985. The deterioration in seizure control occurred despite an increase in polypharmacy, the introduction of new antiepileptic drugs and in some cases increases in dosage.

Adult↗

PubMed2001

Healthy ageing: ageing safely.

The population of the developed world is steadily ageing. In the European Union, approximately 22% of persons are over 60 years of age and this is projected to increase to more than 27% by the year 2020. This has major implications for health care resources and the productive workforce. Ageing is accompanied by a decline in the physiological reserve of all organ systems, compromising homeostasis and resistance to disease. Thus, when disease develops in the elderly it has an increased impact on organ systems not directly involved. This places older people at risk for multiple simultaneous pathologies. Treatment often requires polypharmacy, which often is accompanied by drug interactions and adverse reactions. The pattern of sequential and comorbid disease often means that the later years of life are associated with an accumulating toll of disability, which in turn consumes a high proportion of health-care resources. The major goal of health care in the elderly should be to compress morbidity into the end of the normal lifespan. To achieve this, it will be necessary to redefine our approaches to treatment in the elderly and to develop an evidence base to inform this process.

Aged↗

PubMed2003

Adverse drug reaction risk factors in older outpatients.

BACKGROUND: Adverse drug reactions (ADRs) are common in older (age >or=65 years) outpatients (prevalence, 5%-35%), but there is no consensus on factors that put these patients at high risk for ADRs. Identifying a uniform set of risk factors would be helpful to develop risk models for ADRs for older outpatients and to implement targeted interventions for those patients at high risk for ADRs. OBJECTIVE: The aim of this study was to identify potential risk factors for ADRs in older outpatients through a survey of geriatric experts and to determine their prevalence. METHODS: A comprehensive literature search was conducted to find published articles on ADRs in older patients. Forty-four potential risk factors were identified through the literature search and 6 additional factors were suggested by the expert panel. Through a modified 2-round survey, based on the Delphi consensus method, of an expert panel of 5 physicians and 5 pharmacists, the probability that each of these 50 potential factors could contribute independently to placing an older outpatient at high risk for an ADR was rated on a 5-point Likert scale. After the survey responses were received, means and 95% Cls were calculated. Consensus was defined as a lower 95% confidence limit >or=4.0. Potential risk factors that reached consensus were then applied to a sample of older outpatients to determine their prevalence. RESULTS: After 2 rounds, the expert panel reached consensus on 21 factors, including 12 medication-related factors and 9 patient characteristics. The most prevalent medication-related risk factors were opioid analgesics; warfarin; non-acetylsalicylic acid, non-cyclooxygenase-2 nonsteroidal anti-inflammatory drugs; anticholinergics; and benzodiazepines. The most prevalent patient characteristics included polypharmacy, multiple chronic medical problems, prior ADR, and dementia. CONCLUSIONS: An expert panel was able to reach a consensus on potential risk factors that increase the risk for ADRs in older outpatients. Many risk factors were common in a sample of older outpatients. Future research is needed to determine the predictive validity of these risk factors for ADRs in older outpatients.

Aged↗

PubMed2003

Increase in drug use after admission to Dutch nursing homes.

OBJECTIVE: To study changes in drug use after admission to Dutch nursing homes. SETTING: Six nursing homes near the city of Nijmegen, The Netherlands. DESIGN: Prospective longitudinal study. METHODS: All patients who had been newly admitted to the nursing home were included in the study. Age, gender, residence of the patients before admission, and indication were registered. All prescriptions were registered with start-date and end-date. The nomenclature and subcategory definitions used were those of the World Health Organisation Nordic Anatomical Therapeutic Chemical classification index (ATC) codes. Patients had a follow-up of six weeks. RESULTS: There was a minor, but statistically significant, increase in the mean number of drugs from 5.6 on admission to 5.8 six weeks later. Patients referred from a hospital and patients with a somatic indication were prescribed the highest number of drugs. On admission 5.5% of the patients were not on medication at all, 48% were using 1-2 drugs, and 46% had been prescribed 6 or more drugs. Six weeks after admission, a significant increase in drug use was found in drugs for the nervous system, and drugs for the sensory organs. CONCLUSION: Increase in drug use does not necessarily have to reflect bad prescribing practices. However, in this frail population, continuous drug review is needed to guarantee quality of prescribing and reduce unnecessary polypharmacy.

Aged↗

PubMed2000

Pharmacovigilance based on prescription databases.

Prescription databases are indispensible in drug safety research and surveillance. For suspected rare serious adverse drug reactions, the confirmation and quantitative risk assessment requires proper epidemiological studies. Often prescription databases provide the information on drug exposure for such studies. Aberrant drug utilization in terms of overuse, underuse, polypharmacy etc. may be a threat to the health of the patient, and these aspects can best be studied by prescription databases. In cases of international drug safety alerts, prescription databases may provide information required for rational actions to be taken.

Aged↗

PubMed1998

Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in vitro model of epilepsy.

1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a change in GABA-metabolism have been suggested as mechanisms of action of gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA-transaminase but it also interferes with GABA-release and GABA-uptake. On the basis of these mechanisms of action, a pharmacodynamic interaction of the two antiepileptic drugs could be supposed which might be of relevance in the sense of a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments were carried out on hippocampal slices (n=107) of guinea-pigs (n=70). Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from the bath solution and recorded in the stratum pyramidale of the CA3 region. Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM, 6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100 microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations up to 600 microM, failed to decrease the repetition rate or duration of e.f.p. (n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h (n=11). With simultaneous administration of vigabatrin (100 microM) and gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased down to 8+/-3%, which is significantly different from the values obtained after administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic effect of vigabatrin alone and the enhancement by gabapentin were blocked by the GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results demonstrate that gabapentin is able to augment the antiepileptic effects of vigabatrin significantly. It is possible that a change in the GABA-release machinery is induced by vigabatrin which then can be augmented by gabapentin.

4-Aminobutyrate Transaminase↗

PubMed2000

Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine.

AIMS: To explore drug exposure, frequency of adverse drug reactions (ADRs), types of ADRs, predisposing risk factors and ADR-related excess hospital stay in medical inpatients. METHODS: Structured data regarding patient characteristics, 'events' (symptoms, laboratory results), diagnoses (ICD10) and drug therapy were collected using a computer-supported data entry system and an interface for data retrieval from electronic patient records. ADR data were collected by 'event monitoring' to minimize possible bias by the drug monitor. The causality of each event was assessed in relation to disease(s) and drug therapy. RESULTS: The analysis included 4331 (100%) hospitalizations. The median observation period was 8 days. The median number of different drugs administered per patient and day was 6 and varied between 4 (Q1 ) and 9 (Q3 ) different drugs in 50% of all hospital days. In 41% of all hospitalizations at least one disease-unrelated event could be possibly attributed to drug therapy. Clinically relevant ADRs occurred in 11% of all hospitalizations. In 3.3% of all hospitalizations ADRs were the cause of hospital admission. The incidence of possibly ADR-related deaths was 1.4. Factors predisposing for clinically relevant ADRs were female gender and polypharmacy. ADR-related excess hospital stay accounted for 8. 6% of hospital days. CONCLUSIONS: These data demonstrate the feasibility of the developed 'event monitoring' system for quantitative analysis of ADRs in medical inpatients. With increasing numbers of recorded patients the pharmacoepidemiological database provides a valuable tool to study specific questions regarding drug efficacy and safety in hospitalized patients.

Adverse Drug Reaction Reporting Systems↗

PubMed1999

Clinically significant pharmacokinetic drug interactions between antiepileptic drugs.

Pharmacokinetic interactions between antiepileptics represent a major potential complication of epilepsy treatment because drug combinations are common. This review discusses pharmacokinetic drug interactions of clinical significance involving antiepileptics and cytochrome P450 (CYP). Most commonly used antiepileptics are eliminated through hepatic metabolism, catalysed by the enzymes CYP2C9, CYP2C19 and CYP3A4 and uridine diphosphate glucuronosyltransferase (UDGPT). Antiepileptics are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition. Phenytoin, phenobarbiral, primidone and carbamazepine induce CYP and UDPGT enzymes while valproic acid inhibits them. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential and careful dosage adjustments based on serum drug concentration monitoring and clinical observation are the main methods for reducing the risks associated with these interactions.

Anticonvulsants↗

PubMed2003

Medication use among older Australian veterans and war widows.

This study aimed to review the medications used by a group of Australian war veterans and widows, to identify type and number of medications used and potential inappropriate prescribing. Label details of 4304 medications used by 887 participants were recorded and classified according to the Anatomical Therapeutic Chemical code. The median number of regular medications being used was four (interquartile range 2-7), with a median of one other medication (interquartile range 1-2) being taken as needed. Over half (53%) the participants were taking four or more regular medications. There were 26 potential interactions among 25 people. Polypharmacy was a considerable problem for this group of older Australians.

Aged↗

PubMed2001

Reducing medication regimen complexity: a controlled trial.

OBJECTIVE: To determine if a visual intervention (medication grid) delivered to physicians can reduce medication regimen complexity. DESIGN: Nonrandomized, controlled trial. SETTING: Veterans Affairs medical center. PATIENTS/PARTICIPANTS: Eight hundred thirty-six patients taking at least 5 medications at the time of admission and the 48 teams of physicians and students on the general medicine inpatient service. INTERVENTION: For intervention patients, a medication grid was created that displayed all of the patients' medicines and the times of administration for 1 week. This grid was delivered to the admitting resident soon after admission. MEASUREMENTS AND MAIN RESULTS: For the patients of each team of physicians, we calculated the change in the average number of medications and doses from admission to discharge. The number of medications in the intervention group decreased by 0.92 per patient, and increased by 1.65 in the control group (P <.001). The mean number of doses per day in the intervention group decreased by 2.47 per patient and increased by 3.83 in the control group (P <.001). CONCLUSIONS: This simple intervention had a significant impact on medication regimen complexity in this population. Apparently, physicians were able to address polypharmacy when the issue was brought to their attention.

Adult↗

PubMed2005

Health problems associated with lower urinary tract symptoms in older women. A population-based survey.

OBJECTIVE: To identify health problems associated with lower urinary tract symptoms (LUTS) in an older female population. DESIGN: Population-based cross-sectional survey. SETTING: Third wave for the Tampere Longitudinal Study on Ageing (TamELSA) in 1999-2000. SUBJECTS: A total of 203 women aged 70 years and over. MAIN OUTCOME MEASURES: LUTS categorized as urge symptoms only, voiding symptoms only, and urge and voiding symptoms combined. The health indicators were polypharmacy (> 3 medications), use of sleeping medication, constipation, treated urinary tract infections (UTIs), and neurological, cardiovascular, and musculoskeletal diseases. RESULTS: Of the respondents 16% reported urge symptoms, 22% voiding symptoms, and 26% combined symptoms. In the multinomial logistic regression models, constipation and musculoskeletal diseases were significantly associated with voiding symptoms (OR 4.33; 95% CI 1.62-11.57 and OR 5.25; 95% CI 1.94-14.18, respectively) and with combined symptoms (OR 4.33; 95% CI 1.67-11.21 and OR 2.84; 95% CI 1.17-6.89, respectively). UTIs (OR 2.78; 95% CI 1.09-7.08) were associated with combined symptoms. CONCLUSIONS: Voiding symptoms comprise a significant part of lower urinary tract symptomalogy in older women. Although constipation, musculoskeletal diseases, and UTIs are the main health problems associated with LUTS, other concomitant diseases and medications also need to be assessed in older female patients with LUTS.

Aged↗

PubMed2003

Dosage patterns of antipsychotic drugs for the treatment of schizophrenia in Swedish ambulatory clinical practice--a highly individualized therapy.

OBJECTIVE: To analyse the dosage pattern of antipsychotic drugs for schizophrenia in ambulatory care in Sweden. METHOD: The study was based on a nationwide consecutive weekly random sample of physicians during the period 1991-98 comprising 265,331 visits. RESULTS: In 515 visits (0.19%), antipsychotics were prescribed for schizophrenia. More than one antipsychotic (50 different combinations) was prescribed in 20% of the visits. Patients received higher total daily doses when prescribed more than one antipsychotic drug; mean dose in monotherapy was 210.7 chlorpromazine equivalents (CPZeq) and in polytherapy 406.8 CPZeq. CONCLUSION: Antipsychotics, in contrast to current recommendations, were prescribed as highly individualized therapies in a wide variety of doses and with a high frequency of polypharmacy. The combinations used are often unsuitable and may lead to unnecessary adverse effects.

Adult↗