Drug combination

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... 

Many of these strategies, particularly the ones involving different drug combinations, are largely theoretical at this point and require validation of the concept and determination of optimal regimens. Increased understanding of the mechanisms underlying cancer... 

Amiloride (Midamor) is used in the treatment of CHF and hypertension and is often used with a thiazide diuretic. Spironolactone and triamterene are also used in tiie treatment of hypertension and edema caused by CHF, cirrhosis, and the nephrotic syndrome Amiloride, spironolactone, and triamterene are also available with hydrochlorothiazide, a thiazide diuretic that enhances tiie antihypertensive and diuretic effects of the drug combination while still conserving potassium. 

Toxicology studies must be performed in at least two animal species. If the toxicity profile of the compound is acceptable, then it joins the hit or lead list of compounds to proceed. The metabolism of the compound must be understood and pharmacokinetic studies must be performed in small and large animals. Efficacy studies must be performed in relevant animal models, especially in chimpanzees when more than one candidate is identified and a choice has to be made before proceeding to studies in humans. The ultimate preclinical steps include various studies testing drug combinations in vitro and in vivo, selection of resistant viruses, viral fitness, pyrophosphorolysis, and others. 

Of the NNRTIs that were first approved, nevirapine and, even more so, efavirenz became cornerstones of HIV therapy because of their potential as a component of HAART (Staszewski et al. 1999). The most commonly used NNRTl drug is efavirenz. In addition, nevirapine was shown to effectively prevent HIV transmission from mother to baby. NNRTIs have proven beneficial when included in drug combination (triple or quadruple) therapy, preferably in the presence of protease inhibitors and NRTIs. 

Try to avoid this drug combination Preventative strategies... 

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

Combinations of antiemetics may be the most effective method of preventing PONV for high-risk patients.7,42 Droperidol plus a 5-HT3 antagonist or dexamethasone plus a 5-HT3 antagonist are effective combinations.43,44 Three-drug combinations such as dexamethasone, droperidol, and a 5-HT3 antagonist have not been formally studied but may be a reasonable approach.42... 

Second, if response is inadequate, consider adding a benzodiazepine (lorazepam or clonazepam) for short-term adjunctive treatment of agitation or insomnia if needed Third, if response is inadequate, consider a two-drug combination ... 

First, two-drug combinations lithium3 or valproate3 plus an atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) for shortterm adjunctive treatment of psychotic features (e.g., delusions or hallucinations)... 

First, two-drug combinations lithium3 or lamotrigine6 plus an antidepressant8 lithium plus lamotrigine Alternative anticonvulsants carbamazepine, oxcarbazepine, or valproate... 

Based on the information presented, create a care plan for this patient s HIV/AIDS. Your plan should include (a) a statement of the best drug combinations and reasons supporting each drug recommended, as well as any adverse effects or potential drug-related problems, (b) the goals of therapy, (c) a patient-specific, detailed therapeutic plan, and (d) a plan for follow-up to determine whether the goals have been achieved and adverse effects avoided. 

Cytotoxic chemotherapy is eventually required in most patients with metastatic breast cancer. Patients with hormone-receptor-negative tumors require chemotherapy as initial therapy of symptomatic metastases. Patients who respond initially to hormonal manipulations eventually cease to respond and go on to require chemotherapy. The median duration of response is 5 to 12 months, but some patients will have an excellent response to an initial course of chemotherapy and may live 5 to 10 years or longer without evidence of disease. In general, median survival of patients after treatment with commonly used drug combinations for metastatic breast cancer is 14 to 33 months. The median time to response has ranged from 2 to 3 months in most studies, but this period depends in large part on the site of measurable disease. The median time to appearance of response is between 3 and 6 weeks in patients whose disease is primarily in the skin and lymph nodes, 6 to 9 weeks in patients with metastatic lung involvement, 15 weeks in patients with hepatic involvement, and nearly 18 weeks in patients with bone involvement. Thus it is often the case that an immediate response to therapy is not... 

Similar methods with modifications such as the one by Schutz et al.8 have been in use for over 20 years. In 1968, Ferren and Shane9 published a paper on the differential spectrometric determination of caffeine in soluble coffee and drug combinations. It had the advantage of eliminating a preliminary separation that was required by the earlier method. While the method was successful for coffee, it was not as successful in the determination of caffeine in acetaminophen/phenacetin/caffeine tablets. They proposed that phenacetin was a limiting factor. The official AOAC methods for these methylxanthines in coffee and tea still involve similar methods.10... 

Ferren, W.P. and Shane, N.A., Differential spectrophotometric determination of caffeine in soluble coffee and drug combinations, JAOAC, 51,573,1968. 

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