Drug of last resort

The third congener of phenytoin, phenacemide, is a straight-chain analog of phenytoin. It is a toxic drug of last resort for refractory partial seizures. 

In another study published in the same year, researchers at the CDC found that half of 407 supermarket chickens bought from 26 stores in four states—Georgia, Maryland, Minnesota, and Oregon—carried the sometimes fatal germ E. faecium in a form resistant to Synercid , one of the few drugs of last resort against the infection. 

It is often reserved as the drug of last resort . Vancomycin has increasingly become a first-line therapy in resistant Staphylococcus aureus infections. Vancomycin prevents NAM acid and NAG-peptide subunits from being incorporated into the peptidoglycan matrix the large hydrophilic molecule forms hydrogen-bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides (Figure 20.8). 

Elecainide, proprietary name Tambocor, is a sodium channel blocker with cardiac activity like disopyramide. The drug has significant toxicity in patients with myocardial infarction and has therefore fallen out of favor. For those patients who fail to respond to other sodium channel blockers, it might be a drug of last resort. 

Like pneumococci, methicillin-resistant staphylococci have altered PBPs, giving them a resistance mechanism that cannot be countered easily. Thus, vancomycin has become the drug of last resort to treat methicillin-resistant staphylococci. Ever since E, faecalis was shown to transfer vancomycin resistance to S. aureus in the laboratory in 1992 (41), one of the greatest fears of health professionals universally has been the emergence of vancomycin-resistant, methicillin-resistant staphylococci (42). Recently, such doubly resistant, virtually untreatabie strains have appeared in sporadic cases, confirming the greatest concerns of health care professionals (43). Now the question becomes, will vancomycin-resistant staphylococci emerge faster than the time required to fully develop and test alternatives to vancomycin ... 

Penicillin did not become widely used until after World War II, but even just a decade later, when vancomycin was isolated, people were aware of bacteria that were resistant to penicillin, and the need for different antibiotics was evident. Vancomycin is regarded as the drug of last resort in hospital medicine cabinets, and is reserved for infections resulting from bacteria that are resistant to all other antibiotics, typically MRSA (methicillin-resistant Staphyococcus aureus, the best-known of the hospital superbugs , see p416). 

Despite the early encouraging results described above, the use of ECT in minors then diminished. A constellation of factors may be implicated, including concerns about possible harmful effects (such as how ECT might impair brain development), the advent of psychotropic drugs, the antipsychiatry movement, and negative media depictions of the treatment (Bauer, 1976 Perkins and Tanaka, 1979). ECT in children and adolescents became a controversial treatment of last resort in most countries. There have been attempts in England to prohibit ECT for this age group (Baker, 1994), while ECT has been outlawed for people below 16 years in several states in the United States. 

Diethylstilbestrol continues to be recommended in some centers as one of the agents of last resort when prostate cancer proves refractory to steroid hormones or androgen deprivation therapy has done all it can (1). In a Japanese study in which 16 patients were given a daily intravenous injection of diethylstilbestrol diphosphate 250 mg for 28 days, the short-term response was favorable and the drug was well tolerated (2). 

Finally, some patients may need a completely different type of treatment, such as electroconvulsive therapy (ECT). ECT is often viewed as a treatment of last resort, but it should not be withheld from patients with this disorder who cannot be helped by drug therapy. For patients with psychotic depression, ECT may be a treatment of first choice. 

Both formulations of alprostadil are considered more invasive than VEDs or phosphodiesterase inhibitors. For this reason, intracavernosal alprostadil is generally prescribed after patients fail to respond to or cannot use the less invasive interventions. Intracavernosal alprostadil is preferred over intraurethral alprostadil because the former is more effective than the latter. Also, intracavernosal alprostadil may be preferred in patients with diabetes mellitus, who are accustomed to injectable drug therapy and may suffer from peripheral neuropathies, which decreases the patient s perception of pain upon injection. Intraurethral alprostadil is generally reserved as a treatment of last resort for patients who fail other less invasive and more effective forms of therapy and also refuse surgery. 

Typically, it takes a bacterial strain 15 to 20 years to evolve resistance to antibiotics. The fluoroquinolones, the last class of antibiotics to be discovered until very recently, were discovered more than 30 years ago, so drug resistance has become an increasingly important problem in medicinal chemistry. More and more bacteria have become resistant to all antibiotics—even vancomycin, until recently the antibiotic of last resort. 

Until relatively recently, the last discovery of a new class of antibiotics was in the 1970s, so drug reastance became an increasingly important problem in medicinal chemistry. Vancomycin had been the antibiotic of last resort because there were no reported cases of vancomycin-resistant bacteria until 1989, when more and more bacteria became resistant. 

However, if the patient is receiving second line treatment, components that are not available in the intravenous formulation are administered orally. When no improvement is evident after 7-10 days, clinicians often resort to switching to one of the other regimens. The severe toxicity of pentamidine compared to the other regimens has limited its use. This drug is now used only as a last resort. If switching to pentamidine is being considered, an overlap of two to three days should occur to allow pentamidine to accumulate in the body. 

Phenylbutazone (Butazolidin) is metabolized to oxy-phenbutazone (Phlogistol), and both compounds have all of the activities associated with the NSAIDs. Their use is accompanied by serious adverse reactions, such as anemia, nephritis, renal failure or necrosis, and liver damage. Because of their toxicity, they are prescribed only for the treatment of pain associated with gout or phlebitis or as a last resort for other painful inflammatory diseases resistant to newer and less toxic treatments. Interactions with a large number of other drugs... 

Clofazimine has some activity against M. tuberculosis and is used as a last resort drug for the treatment of MDR tuberculosis. It is primarily used in the treatment of M. leprae and M. avium-intracellulare. Further details are discussed later, under the treatment of leprosy. 

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. 

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