Resistance alternative drugs

There is an expanding body of evidence to suggest that sesquiterpene lactones inhibit the synthesis NO synthetase. One such compound is an ambrosanolides-type sesquiterpene known as cumanin characterized from Ambrosia psilostachya. This sesquiterpene inhibit the enzymatic activity of NO synthetase with an IC50 value of 9.38 xM (49). Another example is the well-known artemisinin, a sesquiterpene used as an alternative drug in the treatment of severe and multidrug-resistant malaria, which inhibits NO synthesis in cytokine-stimulated human astrocytoma T67 cells (50). 

Erythromycin is effective in the treatment and prevention of S. pyogenes and other streptococcal infections, but not those caused by the more resistant fecal streptococci. Staphylococci are generally susceptible to erythromycin, so this antibiotic is a suitable alternative drug for the penicillin-hypersensitive individual. It is a second-line drug for the treatment of gonorrhea and syphilis. Although erythromycin is popular for the treatment of middle ear and sinus infections, including H. influenzae, possible erythromycin-resistant S. pneumoniae is a concern. 

The alternative drugs listed below are usually considered only (1) in case of resistance to first-line agents (2) in case of failure of clinical response to conventional therapy (3) in case of serious treatment-limiting adverse drug reactions and... 

Because of the severe side effects, the restricted tumour spectrum and the acquired or intrinsic resistance, alternative metal-based anticancer drugs are being actively pursued. Ruthenium compounds containing Ru or Ru are considered to be suitable candidates two mthenium(III) complexes have entered clinical trials, trans-[RuCl4(DMSO)(Im)]ImH (NAMI-A, where Im = imidazole) and trans-[RuCl4(Ind)2]IndH (KP1019, where Ind = indazole). This is the mthenium complex, their stmctures are presented in Figure 22.9. There are two... 

F. Alternative Drugs The second-line antimycobacterial drags are used in cases that are resistant to first-line agents they are considered second-line drugs because they are no more effective, and their toxicides are often more serious than those of the major drags. 

B. Other Agents Alternative drugs for leprosy include rifampin (see above) and clofaziinhie. Clofazimine is given in cases of dapsone resistance or intolerance. The drug causes gastrointestinal irritation and marked skin discoloration. 

Flalofantrine is considered to be an alternative drug for treatment of both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum malaria, but its efficacy in mefloquine-resistant malaria may be questionable. The drug is metabolized via N-dealkylation to desbutylhalofantrine by CYP3A4 (Fig. 39.14). The metabolite appears to be several-fold more active than the administered drug. 

The lincomycins, ie. lincomycin and its semisynthetic analogue clindamycin (7-chlorohncomycin), used to be fairly popular antibiotics as alternative drugs for penicillin, especially in known or presumed cases of penicillin allergy or resistance to this antibiotic. Since it has been observed that oral or parenteral administration of both lincomycin and clindamycin may cause fulminating diarrhoea as a sequel to pseudomembranous colitis, their popularity has considerably decreased. 

Alternate ways to interfere with the orexin system may be via inhibition of dipeptidyl peptidases or proteolysis-resistant peptide analogs as shown for other peptides. This could prolong and boost orexinergic signaling. OX-A but not OX-B can enters the brain by simple diffusion via the blood-brain barrier. Abundance of orexins and their receptors in the olfactory bulb and throughout all parts of the central olfactory system may offer transnasal routes for drug application. 

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