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PubMed2005

From mechanisms to management: translating the neuropathic pain consensus recommendations into clinical practice.

Chronic neuropathic pain poses a treatment challenge, and is associated with significant psychologic distress, physical disability, and impaired functioning, which impact the activities of daily living. Efforts to provide relief are often inadequate and/or require polypharmacy. This has spurred interest among researchers and clinicians alike to develop early, intensive treatments that target the molecular and cellular mechanisms involved in pain transduction, transmission, and modulation, or ideally, that prevent neuropathic pain from occurring in the first place. Currently, researchers are attempting to capitalize on our understanding of neuropathic pain pathophysiology to develop drugs that interrupt distinct activities involved in its perpetuation. In this regard, several potential agents (eg, NMDA and AMPA/kainate antagonists) are in phase 2 and 3 clinical trials. In the interim, evolving data and evidence-based neuropathic treatment recommendations provide guidance for selecting first- and second-line medications that alone or in combination offer acceptable neuropathic pain control and allow clinicians to bridge the gap between current knowledge and its application in the clinical setting. Hopefully, as basic and clinical science progresses, further treatment advances and management tools will be found to improve the care of patients who live with neuropathic pain.

Acute Disease↗

PubMed2004

Aging biology and geriatric clinical pharmacology.

Population aging evokes doomsday economic and sociological prognostication, despite a minority of older people suffering significant dependency and the potential for advances in therapeutics of age-related disease and primary aging. Biological aging processes are linked mechanistically to altered drug handling, altered physiological reserve, and pharmacodynamic responses. Parenteral loading doses need only be adjusted for body weight as volumes of distribution are little changed, whereas oral loading doses in some cases may require reduction to account for age-related increases in bioavailability. Age-related reduction of hepatic blood flow and hepatocyte mass and primary aging changes in hepatic sinusoidal endothelium with effects on drug transfer and oxygen delivery reduce hepatic drug clearance. Primary renal aging is evident, although renal clearance reduction in older people is predominantly disease-related and is poorly estimated by standard methods. The geriatric dosing axiom, "start low and go slow" is based on pharmacokinetic considerations and concern for adverse drug reactions, not from clinical trial data. In the absence of generalizable dosage guidelines, individualization via effect titration is required. Altered pharmacodynamics are well documented in the cardiovascular system, with changes in the autonomic system, autacoid receptors, drug receptors, and endothelial function to modify baseline cardiovascular tone and responses to stimuli such as postural change and feeding. Adverse drug reactions and polypharmacy represent major linkages to avoidable morbidity and mortality. This, combined with a deficient therapeutic evidence base, suggests that extrapolation of risk-benefit ratios from younger adults to geriatric populations is not necessarily valid. Even so, therapeutic advances generally may convert healthy longevity from an asset of fortunate individuals into a general social benefit.

Aged↗

PubMed1986

Functional capacity and treatment data from a community based study of patients with rheumatoid arthritis.

A community based study of rheumatoid arthritis was undertaken to determine patient characteristics and the patterns of treatment. Three hundred and eighty subjects were visited in their homes throughout Tasmania (pop. 430 000) by a research team. The median age of the sample was 60 years (interquartile range (IR) 49-69), with a female predominance of 2.65 to 1. The average onset age was 41 years (IR 30-53). Prescribing data indicated that polypharmacy was not common in the community, and that the use of slow acting antirheumatic drugs (SAARDs) and oral corticosteroids was not widespread. At the time of the study 26% of subjects were assayed fully functional--class I of the American Rheumatism Association's (ARA) functional classifications. The functional capacity data provided evidence that the spectrum of rheumatoid arthritis found in the community differed from that found in specialist rheumatology clinics.

Aged↗

PubMed1978

One drug for epilepsy.

We performed prospective trials of phenytoin and carbamazepine, assisted by blood level monitoring, in untreated patients newly referred with grand mal or partial seizures, or both, to a neurological clinic. At the time of follow-up (mean 28.5 months for phenytoin; 12 months for carbamazepine) 76-88% of patients were completely controlled. Twelve per cent of the patients on each drug had further seizures, despite an optimum blood level. When the blood drug concentration was in the optimum range there was a 98% reduction in grand mal attack rate and 92-93% reduction in partial seizure rate. These results suggest that polypharmacy is largely, and possibly totally, unnecessary in newly diagnosed adult epileptics.

Adolescent↗

PubMed1978

Perinatal mortality and morbidity associated with eclampsia.

Out of all the women who were delivered in Cardiff maternity units during 1965-74, 43 developed eclampsia, an incidence of 72/100 000 deliveries. The incidence in residents of Cardiff was 53/100 000 deliveries. None of the mothers with eclampsia died, but 10 of the 47 babies were lost, all but one having been born to women with antepartum eclampsia. The perinatal deaths were mainly associated with chronic placental insufficiency and preterm delivery. The extent to which the wide range of complex drug regimens used influenced perinatal outcome is not clear, although polypharmacy should be avoided. Because eclampsia is rare we advocate that its management should be planned and rehearsed and that a simple, standardised treatment regimen should be used. Failing placental function may be detected by monitoring fetal growth by ultrasound.

Adult↗

PubMed1978

Drug treatment of psychiatric patients in general practice.

The prescribing of psychotropic drugs by general practitioners was assessed by analysing the drug treatment of all patients referred from general practice to a psychiatric outpatient clinic over four years. Of the 287 patients, 220 were taking one or more of 56 different psychotropic drugs at referral, diazepam being the most common. Benzodiazepines and barbiturates had been taken for significantly longer than other drugs, and, of a total of 342 drugs, 61 had been prescribed regularly for over a year. Half of the drugs were considered to be incorrectly prescribed on pharmacological grounds, the main errors being unnecessarily prolonged regular treatment, incorrect dosage (particularly common with antidepressants), and polypharmacy with drugs of similar pharmacological action. A basic grounding in the pharmacology of psychotropic drugs might help practitioners to avoid prescribing errors of this kind.

Adult↗

PubMed1985

Drugs prescribed for self poisoners.

Of 230 adults admitted for self poisoning over two months, 153 (67%) had previously been taking a total of 309 prescribed drugs. Of these patients, 119 (78%) had been given psychotropic drugs (usually benzodiazepines), 81 (53%) obtained them on repeat prescription, and 47 (31%) had been prescribed multiple psychotropic drugs, often in seemingly illogical combinations. The use of these drugs increased progressively with age and most patients took the same drugs in overdosage as they had been prescribed. Psychotropic drugs were prescribed for more than a third of patients with no psychiatric illness and a normal personality, nearly half of those with existing alcohol or drug abuse problems, and for most of the unemployed. Fewer than a third of the patients suffering from depression were prescribed antidepressants but half had been given benzodiazepines and other potentially depressing drugs. Psychotropic drug use, psychotropic polypharmacy, and the repeat prescribing of these drugs were strongly associated with repeated overdosage and, under certain circumstances, with personality disorder, alcohol or drug abuse, unemployment, and conflict with the law. In the long term psychotropic drugs are unlikely to benefit most self poisoners, and they may do positive harm by inducing apathy and depression and predisposing to self poisoning. The incidence of self poisoning (and repeat overdosage in particular) might be reduced by more care and restraint in the prescribing of these drugs.

Adolescent↗

PubMed1993

Acute circulatory support.

Numerous drugs can increase cardiac output, thereby improving tissue oxygen delivery, but often they do this at the expense of increasing myocardial oxygen demand. This may be critical when cardiac function is substantially impaired or ischaemia is the precipitating cause. Using polypharmacy to substantially improve cardiovascular status requires detailed knowledge of the pharmacodynamics and interactions of the available agents so that they may be tailored to the individual patient. In some settings combinations of inotropes and vasodilators may be desirable to minimise cardiac workload. In other instances vasopressors may be necessary to urgently restore a minimum perfusion pressure. This paper reviews the use of this group of drugs as well as the mechanical assist devices that may be used when drugs fail.

Acute Disease↗

PubMed2003

Barriers to accurate diagnosis and effective management of heart failure in primary care: qualitative study.

OBJECTIVE: To ascertain the beliefs, current practices, and decision making of general practitioners in the diagnosis and management of suspected heart failure in primary care, with a view to identifying barriers to good care. DESIGN: A qualitative approach using focus groups with 30 general practitioners from four primary care groups. The sampling strategy was stratified and purposive. The contents of interviews were transcribed and analysed according to the principles of "pragmatic variant" grounded theory. SETTING: North east England. RESULTS: Three categories of difficulties contribute to variations in medical practice and to the reasons why general practitioners experience difficulties in diagnosing and managing heart failure. The first is uncertainty about clinical practice, including lack of confidence in establishing an accurate diagnosis and worries about using angiotensin converting enzyme inhibitors, beta blockers, and spironolactone in patients who are often elderly and frail, with comorbidity and polypharmacy. The second is a lack of awareness of relevant research evidence in what was perceived to be a complex and rapidly changing therapeutic field. Doubts about the applicability of research findings in primary care, and fear of information overload also emerged. The third category consists of influences of individual preference and local organisational factors. Medical training, negative clinical experiences, and outside agencies influenced the behaviour of general practitioners and professional culture. Local factors included the availability of diagnostic services, resources (such as accessible cardiologists), and interactions between professionals in primary or secondary care, and they seemed to shape the practice and decision making processes in primary care. CONCLUSIONS: The national service framework for coronary heart disease stresses that the substandard care of patients with heart failure is unacceptable. This study identified barriers to be overcome across primary and secondary care in implementation strategies that are specific to the locality and multifaceted. Single strategies--for example, the provision of guidelines--are unlikely to have an impact on clinical outcomes, and new, conjoint models of care need to be explored.

Adult↗

PubMedDate not supplied

Development of a replicated database of DHCP data for evaluation of drug use.

This case report describes development and testing of a method to extract clinical information stored in the Veterans Affairs (VA) Decentralized Hospital Computer System (DHCP) for the purpose of analyzing data about groups of patients. The authors used a microcomputer-based, structured query language (SQL)-compatible, relational database system to replicate a subset of the Nashville VA Hospital's DHCP patient database. This replicated database contained the complete current Nashville DHCP prescription, provider, patient, and drug data sets, and a subset of the laboratory data. A pilot project employed this replicated database to answer questions that might arise in drug-use evaluation, such as identification of cases of polypharmacy, suboptimal drug regimens, and inadequate laboratory monitoring of drug therapy. These database queries included as candidates for review all prescriptions for all outpatients. The queries demonstrated that specific drug-use events could be identified for any time interval represented in the replicated database.

Databases, Factual↗

PubMed1988

Concentration-effect relationships with carbamazepine and its epoxide on psychomotor and cognitive function in epileptic patients.

A battery of psychometric tests was administered to 85 patients with epilepsy, of whom 26 were untreated, 40 received carbamazepine monotherapy and 19 took carbamazepine with another anticonvulsant. Carbamazepine alone had little effect on performance, but carbamazepine polypharmacy produced significant impairment. Increasing concentrations of carbamazepine (four tests) and its active metabolite, carbamazepine 10,11 epoxide (seven tests), correlated with decreasing performance in the monotherapy patients.

Adult↗

PubMed1999

Long term effects of refractory temporal lobe epilepsy on cognitive abilities: a cross sectional study.

OBJECTIVE: Intractable epilepsy is related to various transient and chronic brain electric and neurochemical disturbances. There is increasing evidence that chronic epilepsy induces secondary neuronal metabolic and structural decline. However, there is no convincing evidence that the cognitive abilities of patients deteriorate with increasing duration of intractable epilepsy. METHODS: To examine whether duration of refractory temporal lobe epilepsy (TLE) is related to generalised cognitive impairment, psychometric intelligence based on the full scale intelligence quotient (FSIQ, WAIS-R) was determined in 209 patients with unilateral TLE. For analyses of variance (ANOVA) patients were grouped into three categories: <15, 15-30, and >30 years of refractory TLE. RESULTS: An ANOVA and a multiple regression analysis showed that duration of TLE affects FSIQ. Patients with >30 years of TLE performed worse than patients with 15 or 30 years of TLE. The factors side of seizure origin and type of lesion on MRI did not reach significance. A second ANOVA including education as factor showed that in patients with higher educational attainment, the mean FSIQ was stable for a longer duration of TLE than in less educated patients. Retesting 6 months after anterior temporal lobectomy seizure free patients (n=85 of 127) had an higher FSIQ but showed a similar duration effect before and after anterior temporal lobectomy. The variables age at epilepsy onset, education, frequency of interictal epileptiform discharges, frequency of habitual and generalised seizures, serum concentration of antiepileptic drugs, and polypharmacy were statistically controlled. CONCLUSIONS: Psychometric intelligence of patients with a longer duration of refractory TLE were most severely impaired. Consequently, refractory TLE seems to be associated with slow but ongoing cognitive deterioration. It is assumed that epilepsy related noxious events and agents exhaust the compensatory capacity of brain functions. However, as in dementia and Alzheimer's disease, higher educational attainment as an indicator of higher brain reserve might delay the cognitive decline.

Adult↗

PubMed2002

Antiepileptic drugs: coprescription of proconvulsant drugs and oral contraceptives: a national study of antiepileptic drug prescribing practice.

OBJECTIVES: To determine the frequency of coprescription of antiepileptic drugs (AEDs) and drugs with proconvulsant potential and of coprescription of AEDs and low dose oral contraceptives. METHODS: Using information from all 294 fully computerised general practices participating in the General Practice Research Database who entered complete data in 1995, persons were identified who had a prescription for an antiepileptic drug and who had a diagnosis of epilepsy or epileptic seizures in their medical records. Other medication was also recorded. RESULTS: Of women with epilepsy aged 15-45, 16.7% were on the oral contraceptive pill and of 200 on both an enzyme inducing AED and an oral contraceptive, 56% were on formulations with an estrogen content less than 50 microg. This will be associated with increased risk of contraceptive failure and unwanted pregnancy. Over 10% of all AED prescriptions in adults were associated with simultaneous prescription of at least one drug with a potential proconvulsant effect. CONCLUSIONS: Prescribers should be alert to the possibility of pharmacodynamic and pharmacokinetic interactions between AEDs and other medication. With the aging of the population of people with seizures, and the polypharmacy often associated with old age, the likelihood of adversely interacting drug combinations will increase.

Adolescent↗

PubMed1985

Carbamazepine substitution in severe partial epilepsy: implication of autoinduction of metabolism.

Established partial seizures are often refractory to treatment and many patients receive polypharmacy. An attempt was made to improve seizure control with the substitution of carbamazepine (CBZ) for existing treatment in 7 consecutive unremitting cases of partial epilepsy referred by their physicians as 'intractable'. This produced a significant improvement in control of partial (P less than 0.02) and secondary generalized (P less than 0.01) seizures, with 5 patients experiencing a 50% or greater reduction in seizure frequency. A single patient suffered a generalized seizure during the period of changeover. In 3 cases auto-induction of CBZ metabolism resulted in temporary loss of seizure control which was restored by an increase in dose. A policy of planned substitution of CBZ in partial epilepsy previously regarded as intractable may be successful in selected patients. The possible deleterious effect of CBZ auto-induction should be anticipated.

Carbamazepine↗

PubMed1994

Clinical presentation of orthostatic hypotension in the elderly.

Fifty cases of orthostatic hypotension in the elderly are analysed. Three main modes of presentation were identified: (1) falls or mobility problems; (2) mental confusion or dementia; or (3) predominantly cardiac symptoms. Selected case histories are given to illustrate diagnostic difficulties. Medication was responsible for orthostatic hypotension in 66% of patients and striking examples of polypharmacy were encountered. However, 34% of cases were not iatrogenic. Only 14% of patients had overtly postural symptoms. A high index of suspicion is needed to diagnose orthostatic hypotension in the elderly and the condition is often overlooked. The paper provides useful diagnostic clues for clinicians.

Accidental Falls↗

PubMed1996

Diagnosis and management of heart failure in the elderly.

Heart failure is common in the elderly and is associated with a significant morbidity and mortality. It accounts for about 5% of adult medical admissions and the expenditure of 1% of the total National Health Service budget. Clinical presentation in old age may be with the classical symptoms of heart failure but often, due to multiple pathology and low functional ability, presentation is atypical. Both nonspecific symptoms and signs of heart failure, are often a delayed presentation in this population, make diagnosis difficult. Treatment of the failing heart in an older person is similar to the young however, diligence is required when prescribing due to age-related pharmacokinetic changes and co-existent morbidity. This may result in polypharmacy and an increase in drug interactions which themselves may have deleterious consequences. However, knowledge of the aetiology of heart failure in old age and the possible atypical presentation as well as available treatments, will result in better management and improved quality of life and reduced mortality in the elderly heart failure population.

Aged↗

PubMed1985

Geriatric psychopharmacology.

Psychotropic drugs are often used to treat elderly patients suffering from disturbances of behavior, mood, memory, and sleep. Because of increased sensitivity of the aging brain to psychotropic drugs, altered pharmacokinetics, and increased likelihood of polypharmacy as people grow older, specific guidelines for the use of psychotropic drugs should be observed. These guidelines are discussed in the following article.

Aged↗

PubMed2005

[Assessment of the effectiveness of an instrument to identify health an social problems in an elderly population from a primary health care center].

OBJECTIVE: To assess the response rate to a multi-dimensional, self administered questionnaire in patients > or =75 years old attending a primary health care center and to establish the prevalences of problems in the following dimensions: socio-economical, cognitive, morbidity, polypharmacy, physical activity, falls, and activities of the daily living. DESIGN: Cross-sectional descriptive study based on a self-administered questionnaire posted by mail. SETTING: A primary health care center in Barcelona. PARTICIPANTS: A total of 1299 patients > or =75 years old. MAIN MEASUREMENTS: Social surroundings, activities of the daily living, sensorial problems, morbidity, physical symptoms including sphincter's incontinence, cognitive status, and medication use. RESULTS: The response rate was 68% (95% CI, 0.65-0.70). The average age of the women who participated was significantly greater than the one of the men (82.5+/-5.3 vs 81.6+/-5.0, respectively). A significantly greater proportion of women than of men lived single (38.2 vs 10.9%); they had difficulties to maintain its house cosy (15.6 vs 8.8%) and they had difficulties to make ends meet (18.0 vs 13.6%). Globally, there were a greater proportion of women than of men whom they had: medical problems, cognitive problems, depression, and difficulties to carry out activities of the daily living. Overall, subjects that have had difficulties to make ends meet had greater prevalences of problems in all the dimensions of this evaluation. On the other hand, subjects that lived single had lower prevalences of problems in all the dimensions except they had a greater prevalence of depression. CONCLUSION: The multidimensional evaluation in elderly patients by the postal method is an efficient procedure that allows identifying many socioeconomic and health problems. In addition, it is feasible to identify to most fragile subjects and latter on to carry out preventive and curative interventions on them as well as to make their follow up.

Aged↗