Agents and Therapy

Most medical specialities have an interest in trace elements and this reflects their integrated and intrinsic participation in almost all aspects of biochemistry. Promising medical advances may well derive from the development of agents or techniques that manipulate the concentrations of metal ions in vivo. 

Such research into inorganic medicinal chemistry will attract increasing attention, but research into trace element removal using chelation therapy will not decrease. Indeed, reliable experimental data and a sound theoretical understanding of how administered agents modify metal ion distributions in vivo will become more important than ever. 

Secondly, rare metals have been mined, concentrated, and used in a variety of applications that find them interfacing with the human body in greater amounts. This has become increasingly so as the industrial era has changed into the communications era, with more and more of the rarer metals finding widespread use in semiconductors and other devices that drive the computers and microprocessors that we find increasingly in the equipment in our homes, offices, and motor cars. 

Thirdly, the expected average life-span of a baby at birth has almost doubled over the last couple of centuries. This means that the cumulative effects of such non-essential metals become an increasing challenge to an elderly person. Furthermore, such elderly patients may well be deficient in essential or beneficial trace elements, thus magnifying the threat from extraneous metals present as contaminants. 

Fourthly, an increasing number of hereditary, and other, disorders have been traced to metal imbalance scenarios, for example the copper imbalance in Wilson s disease. 

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Among the medical countermeasures, vaccines are available and effective for some of the most important agents, and therapies exist for others. Because of limited resources available to develop vaccines, diagnostic methodologies, and... 

Among retinoids, 13-cis-retinoic acid is known to have not only anti-inflammatory but also sebostatic effects. Therefore it is one of the most potent topical and also systemic agents for therapy of acne. 

Study of the transport of substances across membranes is an example. There is considerable knowledge of the transport of small molecules across living membranes this should be extended to studies of larger molecules. A more complete understanding of the transport of biologically active agents would be particularly important in diagnosis and therapy. 

Select a low-potency or atypical agent and adjust therapy using the lowest possible dose... 

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

With the availability of NSAIDs with COX-2 selectivity, clinicians postulated that these agents would avoid the need to add an additional prophylactic agent to therapy in patients with PUD risk factors. However, selective COX-2 inhibitors have not been shown to be any more effective than the combination of a PPI and a non-selective NSAID in reducing the incidence of ulcers, and questions remain regarding their long-term cardiovascular safety. 

Empiric antibiotic therapy is an appropriate approach to traveler s diarrhea. Eradication of the causal microbe depends on the etiologic agent and its antibiotic sensitivity. Most cases of traveler s diarrhea and other community-acquired infections result from enterotoxigenic (ETEC) or enteropathogenic (EPEC) Escherichia coli. Routine stool cultures do not identify these strains primary empiric antibiotic choices include fluoroquinolones such as ciprofloxacin or levofloxacin. Azithromycin may be a feasible option when fluoroquinolone resistance is encountered. 

Treatment of musculoskeletal disorders involves three phases (1) therapy of an acute injury using the RICE principle, (2) pain relief using oral or topical agents, and (3) lifestyle and behavioral modifications for rehabilitation and to prevent recurrent injury or chronic pain (Fig. 57-3). 

Therefore, despite the 18% and 25% resistance to penicillin and macrolides, the clinical failure rate is less than this. Owing to the empirical treatment of CAP in the outpatient setting, establishing a meaningful clinical failure rate with any therapy is difficult to do. No studies have been performed that established a correlation between clinical failure rates with a particular antimicrobial agent and the percentage of resistant bacterial pathogens. 

Amphotericin B is the mainstay of treatment of patients with severe endemic fungal infections. The conventional deoxycholate formulation of the drug can be associated with substantial infusion-related adverse effects (e.g., chills, fever, nausea, rigors, and in rare cases hypotension, flushing, respiratory difficulty, and arrhythmias). Pre-medication with low doses of hydrocortisone, acetaminophen, nonsteroidal anti-inflammatory agents, and meperidine is common to reduce acute infusion-related reactions. Venous irritation associated with the drug can also lead to thrombophlebitis, hence central venous catheters are the preferred route of administration in patients receiving more than a week of therapy. 

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