Strategies and Approaches in the Development of New Analgesics - Essay Example

? Strategies and Approaches in the Development of New Analgesics May 9, Word Count 1148 Introduction Pain, especially that which is considered neuropathic remains one of the most challenging areas of research as a disease whose population have frequently unmet needs. This pain remains one of the most challenging with great difficulty and frequent and in depth research in an attempt to understand the connection between symptoms and mechanisms (Dray:50, 2008). Most interventions have been focused on meeting and alleviating the symptoms rather than the triggering mechanisms. Introductions of new analgesics are a very slow process in clinical settings and though there is heavy financial support in the development of new analgesics few advances have been made in the preceding decades. It is not well understood how to design and implement studies that are focused on new methods of pain interventions or new analgesics thus many pharmaceutical companies have chosen to withdraw from this market. With a lack of understanding of pain itself, research studies must also consider safety and efficacy in new or novel analgesics. Demonstrations of this are noted in anti-steroidal studies that have shown that through the altering of certain drug molecules enzymes are affected and influenced (Power, 2011). Through this research efficacy was improved though some formulations were withdrawn due to cardiac side effects. In developing creating effective research studies, one barrier has been defining pain; neuropathic, that resulting from damaged tissue, inflammation, pathological that results from a disease process, and that which is associated with potential tissue damaging stimuli. Most analgesics chosen today are from the long-standing standard group of aspirins, opiates, non-steroidal drugs, those that are considered local anesthetics and paracetamol (Power: 19, 2011). Some of the most successful new analgesic formulations have been within the opioids. The introduction of transdermal patches in delivering these analgesics has proven successful in clinical practice. Delivery directly through the patient’s skin reduces side effects and delivers low doses of analgesics (Power: 20, 2011). Transdermal Fentanyl patches are now considered routine therapeutic agents for acute pain. Morphine has also been provided in a novel new method; Depadur, which is a sustained method of relief provided through microcapsules via epidural. This method requires close monitoring of the patient as similar to other routes of administration of morphine nausea, vomiting, and the possibility of over sedation of the patient can occur. Strategies and Approaches in the Development of New Analgesics Strategies that are being used to develop and introduce new analgesics can be grouped into one of five different categories. One approach enhances the utility and/or increases the safety of analgesics with research into the design of novel delivery systems such as the Fentanyl patch and abuse resistant oxycodone. Research has also lead to the development of compounds that target specific mechanisms and compounds have been developed which include a combination of agents that are used to treat pain while also alleviating side effects. Forms of oxycodone have been developed which include ibuprofen and decreases inflammation that may be related to the pathological condition causing the pain (Burgess, & Williams:3753,2010). A fourth strategy has been used in examples such as pregablin; developed for therapeutic indications other than pain though recognized as a precursor in the development and design of varied products for the treatment of pain due to the mechanisms of their action. The minority strategy has been that therapeutics developed from novel mechanisms such as the recognition of the possibilities of N-type calcium channel blockers that are cannabinoid based mechanisms. In order to meet the needs of patients analgesics should be developed with novel molecular mechanisms (Burgess, & Williams:3753,2010). It is of primary importance in research to understand pathophysiological mechanisms that lead to pain and to translate this information into efficacious analgesics that are safe, yet novel. Nerve growth factor research is being studied in clinical trials; sequestering NGF or inhibiting the activation mechanism. One of the most advanced studies in NGF is already in phase II and III clinical trials; tanezumab, which is a monoclonal antibody obtained from an anti NGF antibody (Burgess, & Williams:3754,2010). Through the targeting of sodium channels, patch technologies have been expanded and other classes of drugs such as anticonvulsants are known to bind to sodium channels. Calcium channels are suggested to increase with peripheral nerve damage and it is considered that pregabalin or gabapentin may be useful in blocking these. Therapeutic approaches that target those mechanisms, which are known to regulate the traffic of ion channels, are a future possibility. Potential has also been shown by u-conotoxins. Voltage gated sodium channels have a specific site for binding with these toxins (Norton:2825 2010). These channels are important in regulating cell excitability and control the influx of sodium ions. In this novel research and idea subtypes of these channels have been identified as possible molecular targets in the treatment of pain. Studies now must strive to further understand and identify the precise chemicals in developing a potent yet selective voltage-gated blockade in the hopes of discovering new and effective analgesics for chronic pain. Research into human pain has been able to generate advanced and validated biomarkers. Biomarkers are able to be applied in development programs that are considered advanced. Information and research studies translated from animals through the use of healthy volunteers into the identification of a mechanism based approach in characterizing new analgesic compounds has furthered the advancement of biomarker knowledge (Arendt-Nielsen,& Hoeck :1632,2011). Biomarkers allow a better understanding of those specific mechanisms that are involved in transmission, transduction, and the perception of pain in normal physiological circumstances. The use of this approach allows the temporal and spatial aspects of pain provocation to be standardized and the modulation of pain can be compared quantitatively (Arendt-Nielsen, & Hoeck :1634,2011). Modulation in experimental conditions can be researched and studied allowing for the quantifying of analgesics effects. Conclusion Challenges in new and advanced research in pain and the development of analgesics are numerous. While animals have anatomy and physiology that may resemble that of humans, they are unable to display the multi dimensions of pain such as cognitive and affective changes (Jianren:569,2012). There are very drug development target factors which have an impact on clinical research such as discrepancies between pre and post clinical pain conditions related to the over sanitation of the subjects; a variety of pain measurement and assessment tools and frequently a lack of cohesive understanding of the pharmacodynamics, pharmacokinetic and pharmacogenomics profiles and the interactions between these. Though animal models of tissue are useful receptors, they in no way replace or are reliable indicators of clinical pain. New tools must be developed such as biomarkers that are used in the assessment and evaluation pain in order to further research origins. These biomarkers are now considered a crucial element in drug development and agencies have begun working together to qualify and quantify these novel biomarkers. Finally, new targets that have been suggested as applying in the co-morbidity of conditions; depression and pain, are being given new attention. Works Cited Burgess, G. And Williams, D., 2010. The discovery and development of analgesics: new mechanisms, new modalities. Journal of Clinical Investigation, 120(11), 3753-9. Dray A. (2008). Neuropathic pain: emerging treatments. British Journal of Anesthesia. 101 (1), 48-58. Norton, R 2010, 'Mu-conotoxins as leads in the development of new analgesics', Molecules (Basel, Switzerland), 15,(4) 2825-2844 Power, I. (2011). An Update on Analgesics. British Journal of Anesthesia. 107 (1), 19-24. Arendt-Nielsen, L. And Hoeck, H.C., 2011. Optimizing the early phase development of new analgesics by human pain biomarkers. Expert Review of Neurotherapeutics, 11(11), pp. 1631-51. Jianren Mao, 2012. Current challenges in translational pain research, Trends in Pharmacological Sciences, 33, (11), pp. 568-573, Read More