Drugs enhancing combinations

When oral antidiabetic drug are combined with other antidiabetic drug (eg, sulfonylureas) or insulin, the hypoglycemic effect may be enhanced. Elderly, debilitated, or malnourished patients are more likely to experience hypoglycemia... 

Careful empirical selection of the expression platform for carotenogenesis has included selection of the best strains for stability and degree of accumulation and the selection of compatible drug-resistance combinations and low copy number polycistronic plasmids to enhance product accumulation by decrease of metabolic burden." 5 Matthews and Wurtzel discussed culture and induction conditions - that have been explored in most studies. Most efforts to engineer carotenoid biosynthesis in E. coli focused on the genes and enzymes of the pathway and had a modest effect on improved accumulation. For example, substitution and over-expression of a GGPPS that uses IPP directly (discussed in... 

Trimethoprim, a trimethoxybenzylpyrimidine, selectively inhibits bacterial dihydrofolic acid reductase, which converts dihydrofolic acid to tetrahydrofolic acid, a step leading to the synthesis of purines and ultimately to DNA (Figure 46-2). Trimethoprim is about 50,000 times less efficient in inhibition of mammalian dihydrofolic acid reductase. Pyrimethamine, another benzylpyrimidine, selectively inhibits dihydrofolic acid reductase of protozoa compared with that of mammalian cells. As noted above, trimethoprim or pyrimethamine in combination with a sulfonamide blocks sequential steps in folate synthesis, resulting in marked enhancement (synergism) of the activity of both drugs. The combination often is bactericidal, compared with the bacteriostatic activity of a sulfonamide alone. 

A number of patented technologies for multiparticulate dosage forms have been described recently, such as the Micropump system, which is an osmotically driven coated microparticle system designed to increase the absorption time for rapidly absorbed drugs.59 Combination of water-soluble and water-insoluble polymers could provide enhanced controlled release rates and profiles. A patented technology (COSRx) has been reported to be capable of delivering various sophisticated release profiles. The formulation involves a guar-gum-based tablet and a combination of water-soluble and water-insoluble polymeric tablet coat.60... 

The adverse effects of the combined use of alcohol and cocaine have been reviewed (385). There is little evidence that this combination acts synergistically or that either drug enhances the negative effects of the other. However, the combination leads to the formation of cocaethylene, which may potentiate cardiotoxic effects and the combination has a greater than additive effect on heart rate. Lastly, cocaine antagonizes the learning and psychomotor performance deficits and driving impairment caused by alcohol. 

Drug interactions also may cause problems with different nonprescribed drugs or combinations of prescribed and nonprescribed drugs. The most common examples are mixing drugs that depress the central nervous system. For example, as we said earlier, alcohol and the barbiturates may be lethal in enhancing the sedative effects of each. This drug combination has caused many intentional and accidental deaths. 

In a randomised, erossover study 32 otherwise healthy subjects with hy-pereholesterolaemia were given either ezetimibe 10 mg daily, fluvastatin 20 mg daily or both drugs in combination for 14 days. The combination was well tolerated, no significant pharmacokinetic interaction occurred, and an enhanced lowering of LDL-cholesterol was noted, which was considered to be clinically favourable. However, a case report describes a 52-year-old man taking fluvastatin 80 mg daily who developed elevated creatinine kinase levels 8 weeks after ezetimibe 10 mg daily was added. 

Clinical analysis, immunoassays Proteins, hormones, herbicides, drugs Sensitivity is enhanced combined with fluorescence resonance energy transfer, homogeneous assays... 

In animals, etorphine has produced effects suggestive of an ability to induce drug dependence. Concern had been raised over its abuse potential. Animal studies also suggest that etorphine may enhance contact hypersensitivity to other chemicals. As etorphine has now largely been replaced in veterinary medicine by other drugs or combinations of drugs, these fears are likely to remain unrealised. 

Bergstralh DT, Ting JP (2006) Microtubule stabilizing agents their molecular signaling consequences and the potential for enhancement by drug combination. Cancer Treat Rev 32 166-179... 

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