Toxicity central nervous system , impact

Hansch and Leo [13] described the impact of Hpophihdty on pharmacodynamic events in detailed chapters on QSAR studies of proteins and enzymes, of antitumor drugs, of central nervous system agents as well as microbial and pesticide QSAR studies. Furthermore, many reviews document the prime importance of log P as descriptors of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties [5-18]. Increased lipophilicity was shown to correlate with poorer aqueous solubility, increased plasma protein binding, increased storage in tissues, and more rapid metabolism and elimination. Lipophilicity is also a highly important descriptor of blood-brain barrier (BBB) permeability [19, 20]. Last, but not least, lipophilicity plays a dominant role in toxicity prediction [21]. 

Spatial cooperation is a term coined to describe a situation when disease in one particular anatomic site is missed by one modality but is treated adequately by another. The essence of this is that radiation is a local therapy that will not impact on metastatic disease beyond the planned field borders. Systemic cytotoxic chemotherapy is traditionally used to address the potential distant spread of cancer. In the original description of this mechanism there is no assumption of an interaction between the drugs and radiation with the idea being that the best radiation and best chemotherapy be administered independently of toxicities. The classic example used in several textbooks to illustrate this is the treatment of childhood leukemia with systemic chemotherapy, while their central nervous system, a potential sanctuary site where disease is not treated adequately by chemotherapy, is treated by radiation (28). The reality of the interaction between radiation and chemotherapy is that the dose and timing of radiation are adjusted accordingly to minimize their impact on the neural tissues. 

It is also important to recognize the portal of entry of nanoparticles when considering human toxicity. Nanoparticles can enter the human body through several different ways. The two most recognized pathways are through the airway or the skin. Since inhalation is the pathway of greatest concern and one of the most studied pathways, the discussion here is focused on inhalation. As nanoparticles have been shown to translocate to other organs (104, 105), not only does inhalation impact the pulmonary system, it can also impact the central nervous system. 

Following severe intoxication, patients predominantly display signs of central nervous system dysfunction. Symptoms and signs are described in Table 5.16. Even low COHb levels can have a severe impact on patients with cardiovascular disease and CO toxicity is particularly harmful to the foetus. 

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