Combination Drug Therapy

Other mechanisms of neuronal injury exist in addition to the variety that were discussed above. Because there are multiple mechanisms of injury, it is reasonable to consider that there are also multiple mechanisms of neuroprotection. Therefore, although many single agents have been demonstrated to be protective in animal models, a rational approach to therapy is to consider using multiple pharmacologic agents, which affect, or target, more than one potential mechanism or act at several steps in the ischemic cascade (54). It is possible that combined use of an excitatory amino acid antagonist plus a free-radical scavenger may provide greater neuroprotection than either agent alone. The potential synergistic effect of multiple neuroprotective agents has merit. Although some investigators have demonstrated promising results with this technique (55-57), much additional work is required in both small and large animals using various combinations of agents to determine if this approach will be successful. Combination therapy, however, also has its limitations, which may lead to additional problems. With multiple agents, one must consider the potential increase in adverse events due to possible drug interactions that may lead to altered pharmacokinetics. Finally, with combination therapy, arriving at the best combination of drugs for "the combination" requires thinking mechanistically about which targets or receptors involved in the ischemic cascade we are attempting to alter or block in order to ameliorate the effects of ischemic damage.

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