Clinical pharmacology of gold.

Since the dawn of civilization, elemental gold and gold compounds have been revered and utilized by Shamen and medical practitioners alike for many varied pathological problems. In the 20(th) century following the observations of Jacques Forestier, injectable gold compounds were successfully used for the treatment of rheumatoid arthritis. Of the many compounds developed, gold sodium thiomalate has been the most extensively studied by basic scientists and by clinicians. In the1980s, the oral gold compound auranofin showed promise as a therapeutic contender to injectable gold, but the clinical side effect profile and fear of long term effects of immune suppression by auranofin, resulted in gold sodium thiomalate continuing as the preferred gold compound for rheumatoid treatment. However, the increased use and demonstration of effectiveness of low dose Methotrexate (MTX) in rheumatoid treatment over the last 20 years has resulted in a significant decline in the use of injectable gold sodium thiomalate, this despite the claims and evidence that it remains a useful agent in the management of rheumatoid arthritis. Several authors still contend that the injectable gold compounds can still play a valuable role, and indeed may be the correct first choice in the management of rheumatoid arthritis.

Management of chronic musculoskeletal pain in the elderly: opinions on oral medication use.

The use of oral medication in the treatment of chronic musculoskeletal pain in the elderly requires careful selection of drugs to control pain with consideration for both the physiological state and the presence of disease(s). Recent advances have improved the understanding of biomolecular mechanisms of chronic pain. These include the production of powerful pro-inflammatory cytokines by glial and microglial cells, which then lead to activation of major pain pathways from the periphery through the dorsal horn and supra-spinal pathways to the somatosensory and other higher cortical centres. This has allowed better recognition for intervention with anti-inflammatory agents to control cytokine production (e. g. prednisolone, triamcinolone and other brain-penetrating corticosteroids). Advances in understanding of chronic pain have lead to recognition of neuronal PX2 puringergic receptors as potential sites for drugs to control pain by more selective actions. Pain control in the elderly involves extensive use of analgesics, among them the non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), and various narcotics. Each of these has its drawbacks, mostly related to potential toxicities. Attempts to reduce the serious gastro-intestinal (GI) adverse effects of the NSAIDs by the introduction of the highly selective COX-2 inhibitors (coxibs) have only had limited benefit in reducing these untoward actions. Moreover, the risks of serious cardiovascular (CV) and renal side-effects, though statistically infrequent, are none the less of major concern. Cardio-renal effects have been attributed to some (e. g. diclofenac), but not all (e. g. naproxen) conventional NSAIDs. Here we make recommendations for a selection of certain NSAIDs to be used for pain therapy in the elderly in consideration of their relative safety and pharmacokinetics. While newer formulations of narcotics have given some advance in pain control, the application of this group of drugs requires close supervision in the elderly, especially those with cognitive decline, since drug actions on the central and peripheral nervous systems (CNS, PNS) can result in significant adverse effects of these agents (e. g. constipation, drowsiness, respiratory and cardiovascular decline). Improvements in the safety and effectiveness of musculoskeletal pain therapy in the elderly can only be achieved by identification and frequent re evaluation of the cause of the chronic pain and the impact on the patient's general medical state.