Classic long-term treatment

A variety of debilitating diseases, such as rheumatoid arthritis, inflammatory myopathies, cancers, and a variety of immunological diseases are treated with the classic synthetic glucocorticoids, dexamethasone, and prednisone. However, long-term treatment with these drugs often leads to serious side effects such as fat redistribution, diabetes, vascular necrosis, and osteoporosis. There is currently an intense effort to identify new small molecules that are able to differentially modulate GR to retain the beneficial effects of glucocorticoids and reduce the incidence of unwanted side effects [10]. 

Learned helpnessless in rats is a validated animal model of depression and can be prevented by long-term treatment (7-21 days) with classical antidepressants (e.g., imipramine, clomipramine, fluoxetine), whereas acute treatment is usually ineffective. Single oral administration of a... 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Besides the classical ergotamine/macrolide interaction, attention has been focused on the DHE/triptan interaction with risk of acute vasoconstriction (this raises the difficult question of the acute treatment in patients taking a long term preventive regimen). 

The CATIE project will evaluate the clinical effectiveness of atypical antipsychotics in the treatment of schizophrenia and of Alzheimer s disease. Although antipsychotics were first introduced for the treatment of schizophrenia, they are now used for many other disorders. It is unclear how effective they are and, most important, in view of their rather high cost, how favorably they compare to the first generation of antipsychotics, all of which are available in generic (and thus much less expensive) forms. The CATIE (Clinical Antipsychotic Trials in Intervention Effectiveness) study has specific aims, including the determination of long-term effectiveness and tolerability of the atypical antipsychotics, compared to each and to a typical or classic antipsychotic. At this... 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

A cohort study is a prospective analysis of a population with a particular disease. Participants who are exposed to the study drug and those who are not on treatment are followed for a period of time and observed for development of the disease or result. Information on exposure is known throughout the follow-up period for each patient. The classic example is the use of anthracycline in childhood cancer. A long-term, non-interventional, observational follow-up of 607 children has shown that 5% of patients develop clinical cardiac failure 15 years after treatment. The risk increases with the increase in cumulative doses (Kremer et al., 2001). Once a treatment is associated with certain toxicities, researchers can look at ways to minimise the effect. The relationship... 

Differences in acetylation rates have also been shown to occur with procainamide, but unlike hydralazine, the conclusion is less clear. Henningsen et al. (1975) carried out a prospective study of 42 patients on long-term procainamide treatment they were able to show that 12 patients (29%) developed a classic drug-induced lupus syndrome. The acetylation status was determined on 11 of these 12 patients, 8 proved to be slow and 3 fast acetylation. The authors concluded that... 

---