The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.

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Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.

Psychotropic Drug Use in the Medically Ill: Part I

Certain populations of patients require special considerations when lithium is prescribed. Children and adolescents have higher volumes of body water and more active renal glomerular filtration rates than adults. Their central nervous system is developing and therefore is vulnerable to the impact of substances, including medications such as lithium, that can cause side effects or adverse events. Elderly patients have less body water, slower metabolism, and often comorbid illnesses, so they also require close evaluation and monitoring when prescribed lithium. This paper examines the indications for, pharmacokinetics of, clinical uses of, and side effects of lithium in children, adolescents, and the elderly. Use of alternate mood stabilizers is also addressed briefly.

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Special Considerations: Use of Lithium in Children, Adolescents, and Elderly Populations

Objective This report reviews the efficacy and tolerability of risperidone therapy in elderly patients with chronic psychosis. Methods A computer search was conducted for all patients who were sixty-five years or older at the time of risperidone therapy at the Cleveland VAMC. Data collected included psychiatric diagnosis, risperidone dosage/side effects, concurrent medications, comorbid medical diagnosis, and response to treatment. Treatment response was quantified on a graduated scale. Results Twenty-six patients age sixty-five or older were included in this sample. Mean age of the group was 70.4 years. Mean risperidone dosage was 3.8 mg/day for a mean duration of 251 days. Eighteen of twenty-six patients (69%) had schizophrenia, two of twenty-six (8%) had schizoaffective disorder, two of twenty-six (8%) had bipolar disorder, and four of twenty-six (15%) had other psychotic disorders. Patients had a mean of 2.4 medical diagnoses in addition to their primary psychiatric diagnosis. Twenty-two of twenty-six patients (85%) had clinical improvement on risperidone, and twenty of twenty-six (77%) had improvement that was either marked or moderate. Risperidone therapy was very well tolerated in this elderly population with nineteen of twenty-six patients (73%) remaining on risperidone therapy at completion of this study. Medical illness did not appear to be worsened or complicated by risperidone therapy. Conclusion Risperidone appears to be an effective and well tolerated antipsychotic for elderly patients with chronic psychosis.

Outcome of Risperidone Therapy in Elderly Patients with Chronic Psychosis

The authors review drug biotransformation. Phase I reactions are preconjugation processes that take place through cytochrome P-450—a hepatic mixed function oxidase (MFO) enzyme system with multiple isozymes to metabolize foreign substances. Phase II reactions are conjugation processes of the substrates. Based on the characteristics of the cytochrome P-450 microsomal enzyme systems, the authors explain the clinical phenomena of induction and inhibition of these enzymes when psychotropic agents interact. This article describes both MFO inducers (barbiturates) and inhibitors (cimeditine, fluoxetine and neuroleptic drugs). With this information, clinicians can enhance the ability to monitor drug interactions of psychotropic agents.

Christine J. Sargenti

Papers

Psychotropic drug interactions in the patient with late-onset depression or psychosis. Part 2.

Psychotropic drug interactions in the patient with late-onset psychosis and mood disorder. Part 1.