Treatment resistance mechanisms

Drug resistance in the defined sense, however, is not always the reason for treatment failures. The formation of biofilms may be as well regarded as a resistance mechanism. Cells within such a film withstand the antibiotic treatment. Some antibiotics (e.g. the aminoglycoside tobramycin) penetrate only slowly into the film. A further explanation is the existence of cells living in a non-growing, protected phenotypic state. 

Linalool, 3 231, 232, 233 24 477, 495, 496, 500-503, 546 acid treatment of, 24 502 epoxidation of, 24 502 main producers of, 24 501 Linalool oxide, 24 502 Linalyl, 24 479 Linalyl acetate, 24 501 Linalyl alcohol, 24 500 Linalyl esters, 3 231 Linalyl oxide, 24 503 Lincomycin, registered for use in aquaculture in Japan, 3 221t Lincosamide, bacterial resistance mechanisms, 3 32t Lindane, 13 145-147... 

The current studies were conducted in rodents with I/R ARE, an extensively investigated, albeit imperfect model of the most common and the most treatment-resistant type of clinical AKI. Morigi et al. (Morigi et al, 2004), using rodents with cisplatinum-induced ARE, showed that administration of MSC improved renal function, and MSC appeared to directly contribute to the reconstitution of renal epithelium by transdifferentiation. However, these investigators did not demonstrate that the observed transdifferentiation of MSC is the actual mechanism of renoprotection, and they presented no data regarding the actual numbers of donor cells that undertook the tubular repair. It may be... 

Influenza virus resistant to oseltamivir has not been found in naturally acquired isolates but has been isolated from influenza patients who have undergone treatment with this drug. These resistant strains contain mutations in the active site of neuraminidase and are generally less virulent and infective than nonresistant virus. In vitro passage of influenza virus in the presence of oseltamivir carboxylate can produce mutations in hemagglutinin that decrease the overall dependence of viral replication on neuraminidase however, the clinical relevance of this resistance mechanism is unknown. 

Hornig-Rohan M, Amsterdam JD Clinical and biological correlates of treatment-resistant depression an overview. J Clin Psychiatry 24 220-227, 1994 Horowski R, Wachtel L, Turski L, et al Glutamate excitotoxicity as a possible pathogenetic mechanism in chronic neurodegeneration, in Neurodegenerative Diseases. Edited by Caine DB. Philadelphia, PA, WB Saunders, 1994, pp 163-174... 

Post RM, Chuang D-M Mechanism of action of lithium comparison and contrast with carbamazepine, in Lithium and the Cell Pharmacology and Biochemistry. Edited by Birch NJ. London, Academic Press, 1991, pp 199-241 Post RM, Weiss SRB The neurobiology of treatment-resistant mood disorders, in Psychopharmacology The Fourth Generation of Progress. Edited by Bloom FE, Kupfer DJ. New York, Raven, 1995... 

Preliminary findings indicate that the addition of fluoxetine may increase response or benefit treatment-resistant schizophrenic patients ( 367, 368 and 369). Further, deficit symptoms seemed to improve in some patients, supporting a possible role for 5-FIT2 hypersensitivity as the underlying mechanism 370). Care must be taken to monitor plasma levels of antipsychotics, which may rise when combined with this selective serotonin reuptake inhibitor (SSRI) or other related antidepressants due to their ability to inhibit various CYP 450 isoenzymes. 

Ulmer T, Schaich M, Platzbecker U et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 2004 18 401 08. 

Quinupristin-dalfopristin is approved for treatment of infections caused by staphylococci or by vancomycin-resistant strains of E faecium, but not E faecalis, which is intrinsically resistant probably because of an efflux-type resistance mechanism. The principal toxicities are infusion-related events, such as pain at the infusion site, and an arthralgia-myalgia syndrome. 

The serotonin 1A partial agonist buspirone, whose primary use is in generalized anxiety disorder, is also used as a popular augmenting agent for treatment-resistant depression, particularly in North America (serotonin 1A combo in Fig. 7—30). Its potential mechanism of action as an antidepressant augmenting agent is shown in Figures 7—31 to 7—33. 

Pharmacologists have been attempting to define what it is about clozapine s biochemical mechanism of action that accounts for its special efficacy as well as its side effects. As discussed extensively in this chapter, SDA properties may account in part for reducing EPS, for reducing tardive dyskinesia, and perhaps even for lack of prolactin elevation SDA properties may even help explain improvement in negative symptoms of schizophrenia. However, the concept of SDA does not appear to explain the therapeutic actions of clozapine in treatment-resistant cases because clozapine is superior to other agents that share this property. 

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