Side-Effects Module

Side-Effects Module Decision-support tool to quickly identify and monitor side effects. 

Advances in immunology during the last part of the twentieth century have continued at a rapid rate and cytokines and immune cells having specific markers continue to be defined. A number of natural and synthetic immunotherapeutic agents have been discovered that can modulate components of the normal or aberrant immune system, through stimulation or suppression. However, most of these substances also have inherent adverse side effects. 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

The free permutation of the subunits leads to more than 40,000 possible combinations. It is likely though that in vivo more than 90% of the receptors are composed of only 20 different combinations (21). This plethora of different subtypes suggest that different functional roles are mediated by distinct and separable receptors, and that these could be individually targeted in order to obtain a drug devoid of side effects. It seems likely that the most abundant receptors represent the important combinations and as such, are most likely to be responsible for major functional consequences when targeted. The specific locations of the less abundant receptor populations may result in very selective effects when modulated. 

Diazeniumdiolate compounds have already shown anti-leukemia activity [86]. However, these NO donors release NO systemically and cause severe side effects on the vascular system, so their therapeutical use has been limited. Upon modulation at the... 

Currently the safety and efficacy of 20 is being evaluated in a Phase II study. The program is focused on the evaluation of the sleep induction and maintenance in insomnia patients but also will attempt to demonstrate orexin antagonists effects on improved sleep and side effect profiles compared to current GABAa receptor modulators. 

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