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Pharmacologic management of obstructive lung disease. Current perspectives.

Pharmacotherapy of obstructive lung disease has improved both quantitatively and qualitatively in recent decades: quantitatively with improvements in adrenergic and methylxanthine drugs and qualitatively with the addition of new classes of drugs, such as steroids, cromolyn, and, most recently, anticholinergic agents. Management of airways disease is based upon several principles: near-normal airways function should be aimed for; long-term, systemic, moderate-to-high-dose corticosteroids should be avoided if at all possible; the judicious use of polypharmacy should be undertaken whenever necessary to provide effective treatment while minimizing drug side effects; and the therapeutic program for a given individual should be tailored to that patient's specific responses to various treatments. Available pharmacologic agents have varying efficacies and adverse effects. The various agents may be used in a number of combinations.

Adrenal Cortex Hormones↗

Diabetes in the elderly: diagnosis, pathogenesis, and therapy.

The prevalence of diabetes mellitus increases with age; it occurs in approximately 10 percent of Americans 60 years of age and in 16 to 20 percent of those 80 years old. Type II diabetes mellitus is primarily found in the elderly, and it is estimated that an additional 20 percent of the elderly population has age-associated hyperglycemia, which may be part of a spectrum between normality and type II diabetes. The diabetic group is at risk for both microvascular and macrovascular complications of diabetes, whereas the group with the hyperglycemia of aging may be at risk for macrovascular-type complications. Thus, 40 percent of our senior population has abnormal carbohydrate tolerance and is at risk for diabetic-type chronic complications. The basis for both the diabetic state as well as for the hyperglycemia of aging is probably multifactorial--involving both altered insulin secretion and altered insulin action. Unique problems arise in treating older diabetic patients. Physiologic changes occurring during normal aging, age-associated pathologic processes, the increased prevalence of other chronic diseases, and polypharmacy must all be considered in selecting appropriate therapy for these patients. A rational approach for the maintenance of glucose homeostasis is presented for older patients with diabetes.

Adolescent↗

Age-associated risks of prophylactic anticoagulation in the setting of hip fracture.

PURPOSE: Controversy exists as to whether patient age, either independently or as a marker of concomitant illness or medication use, is associated with the dose or complication rate of warfarin prophylaxis. The aim of this study was to assess this relationship in patients receiving warfarin prophylaxis after hip fracture repair. PATIENTS AND METHODS: We undertook a retrospective cohort study of 215 patients 55 years of age or greater who underwent surgery for a fractured hip between January 1, 1990, and December 31, 1991, and received warfarin prophylaxis. The mean age was 78.9 (SD 9.5) years. The average daily warfarin dose, the decrease in hemoglobin in the postoperative period, and the rate of bleeding complications were assessed. RESULTS: Elderly patients required a significantly lower average daily warfarin dose than younger patients. This effect persisted even after controlling for the number of medical conditions, number of medications on admission, proportion of time the international normalized ration (INR) was in therapeutic range, and gender. Postoperative hemoglobin decrease was associated with patient age as well as with the use of antibiotics postoperatively. Factors associated with bleeding complications included a history of alcohol abuse and a smaller proportion of time spent in the targeted anticoagulant range. CONCLUSIONS: Older age itself and not as a marker for polypharmacy or increased number of medical conditions is associated with lower requirements for warfarin and a greater hemoglobin decrease postoperatively even when the proportion of time the INR fell within the therapeutic range is controlled. Advanced patient age, in this study, was not associated with an increased incidence of bleeding complications.

Age Factors↗

Pharmacotherapy of borderline outpatients.

The charts of 50 outpatients meeting both Diagnostic Interview for Borderlines (DIB) and DSM-III criteria for Borderline Personality Disorder (BPD), 29 outpatients meeting DSM-III criteria for Antisocial Personality Disorder (APD), and 26 outpatients meeting DSM-III criteria for Dysthymic Disorder, as well as DSM-III criteria for some other type of Axis II disorder (dysthymic other personality disorder [OPD]) were reviewed blind to proband diagnosis to determine both the percentage of those in each group who had adequate medication trials and the efficacy of those trials. Borderlines were significantly more likely than antisocial controls to have received an adequate trial of some form of medication. They were also significantly more likely than antisocial controls to have received an adequate trial of anxiolytics and antidepressants. However, they were distinguished at the trend level or better from both antisocial and dysthymic OPD controls by their greater likelihood of having received an adequate trial of neuroleptics, lithium, and polypharmacy. The percentage of adequately treated borderlines who experienced some degree of symptom relief was not significantly different than that found in either control group. However, adequately treated borderlines were significantly less likely than adequately treated dysthymic OPD controls to have had a definite response to pharmacotherapy (i.e., shown marked improvement of target symptoms).

Adult↗

The clinical rationale of cardiac resuscitation.

After failure of external defibrillation, return of cardiac activity with spontaneous circulation is contingent on rapid and effective reversal of myocardial ischemia. Closed-chest cardiopulmonary resuscitation (CPR) evolved about 30 years ago and was almost universally implemented by both professional providers and lay bystanders because of its technical simplicity and noninvasiveness. However, there is growing concern since the limited hemodynamic efficacy of precordial compression accounts for a disappointingly low success rate; especially so if there is a delay of more than 3 minutes before resuscitation is started. There is also increasing concern with the lack of objective hemodynamic measurements currently available for the assessment and quantitation of the effectiveness of resuscitation efforts. Accordingly, the resuscitation procedure proceeds without confirmation that it increases systemic and myocardial blood flows to levels that would be likely to restore spontaneous circulation. Continuous monitoring of end-tidal carbon dioxide (PETCO2) now appears to be a practical measurement which provides a noninvasive quantitative indication of both systemic blood flow and coronary perfusion pressure. Consequently, PETCO2 predicts the likelihood of successful resuscitation and guides the operator who may modify the technique of precordial compression to improve systemic and myocardial perfusion. Among the large polypharmacy for cardiac resuscitation, only alpha-adrenergic agents (which increase coronary perfusion pressure) and especially epinephrine are of proven benefit. Neither buffer agents nor calcium salts appear to improve outcome except under unique conditions. To the contrary, there is increasing awareness of adverse effects of pharmacologic interventions such that they may hinder the return of viable myocardial and cerebral function. This has constrained the routine use of all drugs except for the use of alpha-adrenergic agonists. More invasive interventions by which blood flow is restored such as open-chest cardiac massage or extra-corporeal pump oxygenation (ECPO) are consistently more effective than conventional CPR. Experimentally, both methods promptly restore systemic and myocardial perfusion to viable levels and thereby increase the likelihood that spontaneous circulation is restored even after prolonged cardiac arrest or failure of conventional CPR.

Heart Arrest↗

Salivary phenytoin levels in institutionalized epileptics.

Measurement of phenytoin (PHT) levels in saliva has been advocated as a monitor of plasma levels, and therefore of effective dosage. All studies to date have been performed on outpatients. We have now analyzed whole saliva from 62 mentally retarded, institutionalized, PHT-treated persons with epilepsy. Both PHT and its major human metabolite, 5-(para-hydroxyphenyl)-5-phenylhydantoin (pHPPH) were measured using gas-liquid chromatography. We detected large inter-individual variations in saliva PHT and pHPPH levels. Data were ranked and subjected to statistical analysis according to Spearman. Significant positive correlations were detected between daily PHT dose and plasma total PHT concentration, plasma PHT and salivary PHT, and daily dose and salivary PHT level. When data were categorized and analyzed according to the type of medication being administered in addition to PHT, different results were obtained. Polypharmacy can influence drug and metabolite levels and relationships in institutionalized persons with epilepsy.

Adolescent↗

Field tests for rational drug use in twelve developing countries.

Increasing efforts are being made to improve drug-use practices and prescribing behaviour in developing countries. An essential tool for such work is an objective and standard method of assessment. We present here a set of drug-use indicators produced and tested in twelve developing countries. We describe practical applications, which include the use of indicators to increase awareness among prescribers in Malawi and Bangladesh, to identify priorities for action (eg, polypharmacy in Indonesia and Nigeria, overuse of injections in Uganda, Sudan, and Nigeria, and low percentage of patients who understood the dosage schedule in Malawi), and to quantify the impact of interventions in Yemen, Uganda, Sudan, and Zimbabwe.

Developing Countries↗

Drug metabolism in carcinogenesis and cancer chemotherapy.

Cytotoxic drugs have become invaluable for the clinical oncologist in the treatment of neoplastic disease. Frequently, these therapeutic agents are used in combination in order to combat the heterogeneity imposed by the variable tumor cell biochemistry of the neoplastic cell population. Hence, one could argue polypharmacy has become the rule rather than the exception in cancer chemotherapy. The use of such regimens obviously increases the potential for drug-drug interactions and also may potentiate the effects of interindividual variation in drug metabolism. Altered expression of drug metabolizing enzymes may also predispose certain individuals to cancer through enhanced metabolic activation and decreased detoxication of environmental, dietary and possibly endogenous procarcinogens. Many anticancer drugs can be considered as prodrugs which require metabolic activation to exert their selective cytotoxic effects. Recent molecular and biochemical advances have increased our understanding of the factors which govern the regulation of drug metabolizing enzymes and have improved our knowledge of the metabolism and action of anticancer agents. The aim of this review is not to exhaustively document all the work in the area of drug metabolism in relation to cancer, but to provide a comprehensive update of some of the recent advances in drug metabolism which have helped to rationalize the mechanism of action of some anticancer drugs and which may help to optimize future patient selection for certain novel chemotherapeutic regimens. This review also discusses some of the more recent breakthroughs in the area of carcinogenesis and highlights directions for future studies.

Animals↗

Lithium prophylaxis and the kidney.

We reviewed the records of 44 patients under age 55 with bipolar affective disorder, who were without known systemic illness and receiving lithium prophylactically for a minimum of 6 months. We systematically collected all demographic, family history, and clinical side-effect data. In addition, laboratory results of renal function were compiled. Polyuria was the earliest and most frequent side effect of lithium therapy. Patients receiving other psychotropic medication, plus lithium, showed a significant increased prevalence of polyuria particularly after 3 months of exposure to medication, as compared to patients receiving lithium alone. The onset of polyuria was correlated with duration of lithium treatment and patient's age at initiation of therapy. Our data suggest that polypharmacy, duration of exposure to lithium ion and patient age each predict the development of delayed polyuria, a symptom consistent with interstitial nephritis.

Adult↗

International study of expert judgement on therapeutic use of benzodiazepines and other psychotherapeutic medications: II. Pharmacotherapy of anxiety disorders.

OBJECTIVE: To assemble expert clinical experience and judgement in the treatment of anxiety and related disorders in a systematic, quantitative manner. METHODS: A panel of internationally recognized Experts in treating anxiety and depression was constituted by multistage peer nomination. 90% completed a questionnaire. This report focuses on case vignettes of 7 anxiety disorders followed by questions about relevant therapeutic options. RESULTS: Panelists usually recommended both psychological and pharmacological interventions. Most favored antidepressants, usually tricyclic, for agoraphobia, panic and OCD; beta-blockers for specific social phobia; and benzodiazepines for GAD and adjustment disorder. Some Experts favored polypharmacy, usually an antidepressant and a benzodiazepine. The majority usually advocated pharmacotherapy for 6 months or more. They recommended the same duration of treatment with benzodiazepines and other medications, except for GAD. CONCLUSIONS: The responses of the Expert Panel imply that; (1) most anxiety disorders are serious and merit vigorous, prolonged pharmacotherapy; and (2) antidepressants and benzodiazepines are effective and safe for long-term treatment of these conditions. This outcome contrasts with the widespread apprehension about long-term pharmacotherapy, especially with benzodiazepines, and some regulatory views.

Anti-Anxiety Agents↗

Effect of training on the clinical management of malaria by medical assistants in Ghana.

Malaria accounts for over 40% of all outpatient consultations in Ghana. A common drug use problem associated with its treatment with chloroquine is over- and under-dosage and a preference for the intramuscular route of administration. Inadequate treatment is an important factor in the selection of resistant strains of malaria parasites. To ensure the proper management of diseases at health centres the Ministry of Health instituted an in-service training programme for medical assistants in 1987. We evaluated the effect of this training on the clinical management of malaria using a quasi-experimental design. Three methods of data collection were used; prescription survey, assessment questionnaires and focus group discussions. Our findings revealed that gains in knowledge following the training had deteriorated within a year. There was also a discrepancy between knowledge and practice of malaria treatment. This was shown by over- and under-dosing of chloroquine in children and adults respectively. There was also overwhelming preference (85% of all cases) for injections and a high tendency towards polypharmacy (average of five drugs per visit). The motivating reasons for these were mainly socio-cultural and included patient demand and attitudes, prescriber self interests and stereotypes and the daily practical challenges of the community. While paying greater attention to supervision of clinical work at health posts, consideration must be given to socio-cultural context of drug use in any such future training programmes if rational use of drugs is to be achieved.

Adult↗

Polymedication and medication compliance in patients with chronic non-malignant pain.

Most reports of polymedication among patients with chronic non-malignant pain have relied only on the patient's statements which have been proven to be unreliable regarding actual drug consumption. This study investigates the incidence of polymedication and medication compliance in these patients by applying objective methods. One-hundred-nine consecutive patients predominantly with facial, neuropathic or back pain were interviewed about present medication at first admission to the pain clinic. Reports were verified by toxicological urine screening, mainly with thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) coupling. Follow-up investigations of 61 patients were conducted within 1 and 24 months after beginning therapy. Polymedication--here defined as daily intake of 3 or more preparations--was found in 41 patients (38%) in the initial investigation. In only 74 patients (68%) did the results of urine screening correspond with their reports: 23 patients (21%) concealed the consumption of drugs, and 2 patients (2%) did not take their medications. Ten cases were not interpretable. Fifty-four percent of the drugs concealed were psychotropic substances, mostly benzodiazepines, and 42% were analgesic combinations, partly with psychotropic additives. Drug intake was concealed significantly more often with polypharmacy which was occurring more frequently in patients with headache or facial pain, longer duration of pain, young age, psychiatric diagnosis and history of substance abuse. Patients with initial non-compliance were more likely to conceal drug consumption in follow-up investigations as well (P = 0.05). Therefore, screening for medication compliance in patients with chronic non-malignant pain is recommended, especially in those with the abovementioned risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Functional status of older persons with chronic mental illness living in a home setting.

The purpose of the study was to determine the functional status of older persons with chronic mental illness. One hundred subjects living in their homes were interviewed in face-to-face interviews using the Older Adult Resources Survey (OARS) to determine functioning in five areas: social, economic, mental, physical, and activities of daily living. Pearson product moment correlation showed significant relationships among all functional scores. Twenty-nine percent of the total sample had social relationships of poor quality. Thirty-five percent of subjects had severe economic impairment. The majority (53%) of subjects had psychiatric symptoms. The most common psychiatric diagnosis was depression (42%), followed by schizophrenia (22%), and bipolar illness (13%). Twenty-nine percent of subjects had a serious medical problem that required medical treatment. Cardiovascular diseases were the most frequently reported (92%), followed by arthritis (45%) and urinary tract disorders (19%). All subjects perceived that their physical health had deteriorated over the 5 years. Polypharmacy and drug misuse were common among the sample. A mean of four prescribed drugs was taken daily over the past month. Psychotropic (83%), antihypertensive (32%), and cardiac (20%) medications were the most frequently prescribed drugs. Twenty-five percent of the sample regularly required assistance with at least four activities of daily living.

Activities of Daily Living↗

A nurse-managed inpatient program for patients with chronic mental disorders.

The deinstitutionalization movement has left a legacy of need for appropriate care for inpatients with chronic refractory mental illness. This article describes a nurse managed program for such patients based on the principles of a therapeutic milieu. The program was formally defined for a 6-month period with an effort to include outcome measures for program evaluation. Multidisciplinary treatment team planning with a psychiatric nursing clinical specialist as team leader provided a format for putting therapeutic concepts into practice. The nurse clinical specialist and two nurse practitioners served as case managers as well as primary care providers. Program evaluation showed that cost-effective quality care could be achieved with a reduction in polypharmacy and overall neuroleptic usage. The notion of a restraint appropriate environment, with the goal of minimizing restraint use, was introduced and put into practice.

Adult↗

Antidepressant use in the elderly: association with demographic characteristics, health-related factors, and health care utilization.

The characteristics of antidepressant use and its correlates were assessed in the four Established Populations for Epidemiologic Study of the Elderly (EPESE) communities (n = 13,074). Women were significantly more likely to be treated with an antidepressant drug than men, and African-Americans were significantly less likely than whites to be using antidepressant medication. Of the health-related measures, poor self-perceived health, polypharmacy, disabilities in activities of daily living, and a history of stroke were associated with the use of antidepressants. Each utilization of health care variable, (number of doctors visits, overnight hospitalization in the past year, and use of a regular doctor), was associated with antidepressant use in at least two of the four communities. After entering variables in a multivariate regression model, higher antidepressant use was significantly associated with female gender, race, poor self-perceived health, and a greater number of contacts with doctors in the past year.

Aged↗

Age and severe adverse drug reactions caused by nifedipine and verapamil. Gruppo Italiano di Farmacovigilanza nell' Anziano (GIFA).

The association of age with risk for severe adverse drug reactions (SADRs) was studied in 2371 and 862 hospitalized patients taking nifedipine and verapamil, respectively. Nifedipine caused hypotension (n = 22), tachycardia (n = 3), and acute renal failure (n = 1) (total SADR rate, 1.1%, 26/2371). Verapamil caused hypotension (n = 3), bradycardia (n = 9), and atrioventricular blocks (n = 2) (total SADR rate, 1.6%, 14/862). The mean age of patients with and without SADRs was for nifedipine 77.1 +/- 1.7 and 71.8 +/- 0.8 years, respectively (p < 0.05), and for verapamil 73.4 +/- 2.9 and 73.1 +/- 0.4 years, respectively. Sex, length of stay, comorbidity, polypharmacy, intake of slow-release preparations, daily dosage, and new intake of calcium antagonists were examined as potential confounders of the age-SADR association. After adjusting for potential confounders, age was significantly and independently associated with SADRs caused by nifedipine, but not with SADRs caused by verapamil (OR = 1.69, 95% CI = 1.05-2.72 and OR = 1.06, 95% CI = 0.63-1.68 for 10-year increase, respectively). Although nifedipine and verapamil did not have significantly different rates of SADRs, an age-related gradient was found only for nifedipine.

Age Factors↗

Survey of 260 epileptic patients treated with oxcarbazepine (Trileptal) on a named-patient basis.

We report the clinical findings on all 260 epileptic in- and out-patients of a Dutch epilepsy centre ever treated with oxcarbazepine on a named-patient basis. All but three patients had been previously treated, in vain, with carbamazepine. Of 260 patients, exposed for 935 patient-years, 161 were still treated on reference date, the longest duration of oxcarbazepine treatment being 119 months. Fourteen patients were lost to follow up. Four successfully stopped treatment after full control of their epilepsy for over three years. Seven stopped because they got worse instead of better. Seventy-three did not benefit sufficiently to continue on OCBZ in view of alternative treatment possibilities. In one patient the final diagnosis was pseudo-seizures. The drug is particular useful in patients who require polypharmacy and patients with adverse effects to carbamazepine.

Adolescent↗

Triple antiplatelet therapy does not increase femoral access bleeding with vascular closure devices.

BACKGROUND: The use of arteriotomy closure devices (CDs) to achieve hemostasis after femoral artery access in percutaneous coronary intervention is steadily increasing. However, the safety information with these devices in the era of triple antiplatelet therapy is limited. METHODS: We reviewed prospectively collected data from the Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET), where all patients received aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitor therapy. At the treating physician's discretion, manual compression (MC) or a vascular hemostasis device was selected following femoral angiography. Patients receiving MC were to have sheaths removed 2 to 6 hours postprocedure when the activated clotting time was < or = 175 seconds. RESULTS: Of 4809 patients, 4736 had femoral access, and 985 of these had a CD (Perclose 47%, Angio-Seal 43%, VasoSeal 5%, and other 5%). The MC and CD groups were similar regarding most demographic characteristics, including age, systolic blood pressure, and weight, but those with MC were more often female, diabetic, and had history of peripheral vascular disease. Patients with a CD had a lower ischemic event rate suggesting they were a lower risk cohort overall. There were no differences in major bleeding at the access site (0.4% vs 0.5%, P =.588), minor bleeding at the access site (1.9% vs. 3.1%, P =.142) or transfusions (0.8% vs 1.0%, P =.513) between the MC and CD groups, respectively. CONCLUSIONS: In contemporary percutaneous coronary intervention practice, with appropriate patient selection, a CD can be safely utilized despite aggressive polypharmacy for procedural anticoagulation.

Angioplasty, Balloon, Coronary↗