Select Agents

The proposal that NO or its reactant products mediate toxicity in the brain remains controversial in part because of the use of non-selective agents such as those listed above that block NO formation in neuronal, glial, and vascular compartments. Nevertheless, a major area of research has been into the potential role of NO in neuronal excitotoxicity. Functional deficits following cerebral ischaemia are consistently reduced by blockers of NOS and in mutant mice deficient in NOS activity, infarct volumes were significantly smaller one to three days after cerebral artery occlusion, and the neurological deficits were less than those in normal mice. Changes in blood flow or vascular anatomy did not account for these differences. By contrast, infarct size in the mutant became larger... 

Non-selective 3-blockers, including those in ophthalmic preparations, may cause asthma symptoms, and these agents should be avoided in asthmatics unless the benefits of therapy outweigh the risks.1 In asthmatic patients requiring 3-blocker therapy, a Pi-selective agent should be chosen. Because selectivity... 

NSAIDs are classified as non-selective (they inhibit COX-1 and COX-2) or selective (they inhibit only COX-2) based on degree of cyclooxygenase inhibition. COX-2 inhibition is responsible for anti-inflammatory effects, while COX-1 inhibition contributes to increased GI and renal toxicity associated with non-selective agents. Since the antiplatelet effect of non-selective NSAIDs is reversible, concurrent use may reduce the... 

The dual inhibition of acetylcholinesterase and butyrylcholinesterase may lead to broader efficacy. As acetylcholinesterase activity decreases with disease progression, the acetylcholinesterase-selective agents may lose their effect, while the dual inhibitors may still be effective due to the added inhibition of butyrylcholinesterase. However, this has not been demonstrated clinically. 

Inquire about carryover sedation and other side effects associated with the selected agent. Use a lower dose or select a drug with a shorter duration of action if the patient experiences carryover sedation. 

NSAIDs are associated with gastrointestinal, renal, hepatic, and central nervous system toxicity and may increase blood pressure. NSAIDs that are selective for the cyclooxygenase-2 (COX-2) isozyme are less likely to cause gastrointestinal complications but may increase the risk of cardiovascular events. They are no more effective than nonselective NSAIDs. Selective agents should be reserved for patients at high risk of gastrointestinal complications and low risk for cardiovascular events. 

Pediatric Doses of Selected Agents Used in Bacterial Meningitis Treatment... 

The extent to which the cell line supports appropriate expression of the cDNA. The level of expression achieved is determined by interactions of the vector/ expressed protein with the cell. These interactions include the strength of the promoter (weaker promoters can be compensated for by using a vector which is present at high copy number), the adequacy of the selective agent (not all agents are toxic to all cells), the stability of the expressed protein (some proteins may be rapidly degraded in some cells), and whether the expressed protein exerts any deleterious effects on the viability of host cells (some efflux transporters could deplete the cell of essential components). Finally, transporters must be expressed in a polarized manner in the host cell (i.e., preferentially on either the basolateral or apical side of the cell). 

Nonspecific NSAIDs bhd to Cox-1 and Cox-2 Cox-2 selective agents bind In Cqx-2 pocket... 

Marker gene Prod uct /phenotype Sources Selective agent Reft... 

They are on the HHS Select Agents list, the USDA High Consequence list, the Australia Group Core list, and are listed as a Category A Potential Terrorism Agent by the CDC. 

They are on the HHS Select Agents list and the Australia Group Core list. 

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