Various forms of chemically induced liver injury and their detection by diagnostic procedures.
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A large number of chemical agents, administered for therapeutic or diagnostic purposes, can produce various types of hepatic injury by several mechanisms. Some agents are intrinsically hepatotoxic, and others produce hepatic injury only in the rare, uniquely susceptible individual. Idiosyncrasy of the host is the mechanism for most types of drug-induced hepatic injury. It may reflect allergy to the drug or a metabolic aberation of the host permitting the accumulation of hepatotoxic metabolites. The syndromes of hepatic disease produced by drugs have been classified hepatocellular, hepatocanalicular, mixed and canalicular. Measurement of serum enzyme activities has provided a powerful tool for studies of hepatotoxicity. Their measurement requires awareness of relative specificity, knowledge of the mechanisms involved, and knowledge of the relationship between known hepatotoxic states and elevated enzyme activities. (+info)
Psychotropic drug use among women.
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The consistent 2:1 ratio of women to men in the receipt of prescriptions for psychotropic drugs is reflected in the higher rates for women of neurotic illness, symptoms of both physical and mental discomfort, and help-seeking and drug-taking behaviour. Physicians' perceptions of the problems presented by their male and female patients influence their prescribing of these drugs. Recent statistics in Ontario indicate that greater use of physicians' services by women is an inadequate explanation of the higher rate of prescribing of psychotropic drugs to women. A longitudinal study of a large insured population in Ontario showed that almost twice the proportion of females, compared with males, received a prescription for psychotropic drugs in 1970-71 and in 1973-74, a higher proportion of females received multiple prescriptions for each drug class, and males were more likely than females to have received only one prescription in a year. (+info)
Alternative insurance arrangements and the treatment of depression: what are the facts?
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Using insurance claims data from nine large self-insured employers offering 26 alternative health benefit plans, we examine empirically how the composition and utilization for the treatment of depression vary under alternative organizational forms of insurance (indemnity, preferred provider organization networks, and mental health carve-outs), and variations in patient cost-sharing (copayments for psychotherapy and for prescription drugs). Although total outpatient mental health and substance abuse expenditures per treated individual do not vary significantly across insurance forms, the depressed outpatient is more likely to receive anti-depressant drug medications is preferred provider organizations and carve-outs than when covered by indemnity insurance. Those individuals facing higher copayments for psychotherapy are more likely to receive anti-depressant drug medications. For those receiving treatment, increases in prescription drug copayments tend to increase the share of anti-depressant drug medication costs accounted for by the newest (and more costly) generation of drugs, the selective serotonin reuptake inhibitors. (+info)
Outpatient antidepressant utilization in a Dutch sick fund.
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OBJECTIVE: To identify quality improvement opportunities in the management of depression by evaluating patterns of antidepressant use and concurrent use of anxiolytics or sedative/hypnotics among patients who initiated therapy with amitriptyline, fluoxetine, fluvoxamine, or paroxetine. DESIGN: A longitudinal, retrospective study using electronic prescription data from a Dutch sick fund, ZAO Zorgverzekeringen. PATIENTS AND METHODS: The study patients (n = 2,554) initiated therapy between October 1, 1994 and December 31, 1995. Follow-up periods were 6 months (antidepressant use) and 60 days (concurrent anxiolytic and sedative/hypnotic use). RESULTS: The three key findings were as follows: (1) the majority of patients received less than 4 months of therapy (more common for patients receiving amitriptyline); (2) the average daily doses for initial prescriptions for all four study drugs were below the recommended therapeutic minimums for depression (overall and final amitriptyline doses also were consistently low); and (3) the incidence of concurrent anxiolytic and sedative/hypnotic use during days 2-60 after antidepressant therapy initiation was 18.2%. CONCLUSION: The study suggests that patients in this Dutch sick fund were not likely to receive either adequate antidepressant doses or adequate durations of therapy relative to Dutch guidelines for the treatment of depression. These findings are consistent with findings in other Dutch, European, and US studies and may present opportunities for quality improvement. (+info)
Amitriptyline and procainamide inhibition of cocaine and cocaethylene degradation in human serum in vitro.
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Amitriptyline (AMI) and procainamide (PA) have been reported to inhibit the activity of human plasma butyrylcholinesterase, an enzyme important in the metabolic degradation of cocaine (COC) and its ethyl analogue cocaethylene (CE). Because both AMI and PA may be used in the treatment of COC intoxication and abuse, the effect of high pharmacological concentrations of these compounds on the degradation of COC and CE in pooled human serum was studied. AMI (1.8 micromol/L) modestly inhibited the degradation of COC by 4.2% and of CE by 4.0%. PA (42.5 micromol/L) profoundly inhibited degradation of COC by 42.7% and of CE by 47.2%. In contrast, lithium carbonate (1 mmol/L, control) showed no inhibition of degradation of either COC or CE. These results suggest that AMI and PA may prolong the half-life of COC and CE in human serum. (+info)
Drug-induced heart failure.
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Heart failure is a clinical syndrome that is predominantly caused by cardiovascular disorders such as coronary heart disease and hypertension. However, several classes of drugs may induce heart failure in patients without concurrent cardiovascular disease or may precipitate the occurrence of heart failure in patients with preexisting left ventricular impairment. We reviewed the literature on drug-induced heart failure, using the MEDLINE database and lateral references. Successively, we discuss the potential role in the occurrence of heart failure of cytostatics, immunomodulating drugs, antidepressants, calcium channel blocking agents, nonsteroidal anti-inflammatory drugs, antiarrhythmics, beta-adrenoceptor blocking agents, anesthetics and some miscellaneous agents. Drug-induced heart failure may play a role in only a minority of the patients presenting with heart failure. Nevertheless, drug-induced heart failure should be regarded as a potentially preventable cause of heart failure, although sometimes other priorities do not offer therapeutic alternatives (e.g., anthracycline-induced cardiomyopathy). The awareness of clinicians of potential adverse effects on cardiac performance by several classes of drugs, particularly in patients with preexisting ventricular dysfunction, may contribute to timely diagnosis and prevention of drug-induced heart failure. (+info)
The effects of detection and treatment on the outcome of major depression in primary care: a naturalistic study in 15 cities.
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BACKGROUND: This study reports the responses of patients with confirmed depressive illnesses to different treatments in the WHO Mental Disorders in General Health Care study, conducted in 15 cities around the world. AIM: To discover how depressions recognized by the doctor compare with unrecognized depressions, both in terms of the initial illnesses and their outcomes, and to compare the outcomes of those depressions treated with antidepressants with those treated with daytime sedatives. METHOD: The design of the study was naturalistic, in that physicians were free to treat patients however they wished. Patients with confirmed depressive illnesses were assigned to four groups: treatment with an antidepressant; treatment with a daytime sedative (usually a benzodiazepine); patients recognized as having depression by the physician but were not offered drug treatment; and patients unrecognized as having depression by their physician. RESULTS: Both groups receiving drugs had illnesses of equal severity, were demographically similar to one another, and had similar previous histories of depression. Those receiving antidepressants had significantly fewer overall symptoms and fewer suicidal thoughts than those treated with sedatives. By the end of one year, differences between the groups had disappeared: patients not given drugs had milder illnesses but did significantly better than those receiving drugs, both in terms of symptoms lost and their diagnostic status. Unrecognized depressions were less severe than recognized depressions, and had a similar course over the year. CONCLUSIONS: Patients receiving antidepressants were better in terms of overall symptoms and suicidal thoughts than those treated with sedatives at three months, but this advantage does not persist. Depression emerges as a chronic disorder at one-year follow-up--about 60% of those treated with drugs, and 50% of the milder depressions, still meet criteria for caseness. The study does not support the view that failure to recognize depression has serious adverse consequences, but, in view of the poor prognosis of depression, measures to improve compliance with treatment would appear to be indicated. (+info)
Depressive state with anxiety in repeated cold-stressed mice in forced swimming tests.
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The effects of various types of stress and drugs were studied to assess mouse performance in forced swimming tests, following characterization of SART (specific alternation of rhythm in environmental temperature) stress. Immobility time in the test decreased in mice subjected to SART, acute cold and restraint stress. No change was noted due to chronic cold stress or repeated fasting. The shortened time did not recover even 24 hr after the end of SART and chronic restraint stress. The time in SART-stressed mice finally recovered at 5-7 days. Shortening of immobility time in SART-stressed mice was inhibited by diazepam and repeated imipramine but not by lithium carbonate. In chronic restraint-stressed mice, this time was inhibited by repeated lithium carbonate but not diazepam or imipramine. SART stress would thus appear related to anxiety and depression and may be useful for detecting new types of antidepressants. (+info)