Triple therapy

The main clinical use of COMT inhibitors is as adjunct (or additional adjunct) in the therapy of Parkinson s disease. The standard therapy of Parkinson s disease is oral L-dopa (as a drug levodopa) given with a dopa decarboxylase (DDC) inhibitor (e.g. carbidopa and benserazide), which does not reach the brain. When the peripheral DDC is inhibited, the concentration of 3-O-methyldopa (3-OMD), a product of COMT, in plasma is many times that of L-dopa. Since the half-life of 3-OMD is about 15 h, compared to about 1 h for L-dopa, the concentration of 3-OMD remains particularly high during chronic therapy, especially if new slow release L-dopa preparations are used. A triple therapy (L-dopa plus DDC inhibitor plus COMT-inhibitor) will... 

To further improve sustained virologic response rates, different treatment approaches are currently under investigation. For example, individualized therapy durations on the basis of the HCV RNA concentration at baseline and early during therapy are the subject of clinical studies (Berg et al. 2006 Zeuzem et al. 2005a). In addition, triple therapy with other antiviral compounds, such as amantadine, has been evaluated in multiple studies, leading to contradictory results (Mangia et al. 2004). 

Traditional triple-therapy immunosuppressive regimens have consisted of a calcineurin inhibitor, an antiproliferative or ToR inhibitor, and corticosteroids. In recent years, many protocols have focused on corticosteroid sparing or avoidance. Avoidance or sparing of corticosteroids has been supported in the literature, although more studies are needed to better characterize which patients should follow these protocols.36-39... 

Furuta T, Shirai N, Takashima M et al. Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Clin Pharmacol Ther 2001 69[3] 158—168. 

Gisbert JP, Pajares JM Helicobacter pylori rescue regimen when proton pump inhibitor-based triple therapies fail. Aliment Pharmacol Ther 2002 16 1047-1057. 

Wong WM, Gu Q, Lam SK, Fung FM, Lai KC, Hu WH, Yee YK, Chan CK, Xia HH, Yuen MF, Wong BC Randomized controlled study of rabeprazole, levofloxacin and rifabutin triple therapy vs. quadruple therapy as second-line treatment for Helicobacter pylori infection. Aliment Pharmacol Ther 2003 17 553-560. 

First-line treatment with quadruple therapy using a PPI (with bismuth, metronidazole, and tetracycline) achieves similar eradication rates as PPI-based triple therapy and permits a shorter treatment duration (7 days). However, this regimen is often recommended as second-line treatment when a clarithromycin-amoxicillin regimen is used initially. All medications except the PPI should be taken with meals and at bedtime. 

The therapy prescribed is a 1-week triple therapy regimen consisting of amoxicillin, clarithromycin and omeprazole against Helicobacter pylori infection. 

Proton pump inhibitors such as omeprazole may mask the symptoms of gastric cancer. Omeprazole is best avoided during breast-feeding. The prescription is indicative of triple therapy used as eradication therapy in H. pylori infection. 

Clarithromycin is a macrolide that has a longer half-life than erythromycin so is administered twice daily. Clarithromycin is more active against Grampositive organisms than erythromycin. Clarithromycin may be used in combination with amoxicillin, for example, as part of triple therapy used for the eradication of Helicobacter pylori. 

Triple therapy (esomeprazole, lansoprazole, omeprazole, rabeprazole)- In combination with clarithromycin and amoxicillin. 

H. pylori eradication to reduce the risk of duodenal ulcer recurrence Triple therapy... 

Triple therapy- 30 mg lansoprazole plus 500 mg clarithromycin and 1 g amoxicillin all taken twice/day for 10 to 14 days. 

Triple therapy (omeprazole/clarithromycin/amoxiclllin)- Omeprazole 20 mg plus clarithromycin 500 mg plus amoxicillin 1000 mg each given twice/day for 10 days. If an ulcer is present at the initiation of therapy, continue omeprazole 20 mg for an additional 18 days. 

Triple-therapy regimens These regimens have proven to be very effective in eradicating H. pylori. The primary disadvantage of these regimens is compliance because of the variety and number of medications used. Likewise, adverse effects are more common in patients taking these regimens compared with alternatives. 

Indicative annual cost per person for triple therapy in Africa... 

A triple therapy regimen with combinations of clarithromycin or azithromycin plus ethambutol plus rifabutin is the current standard of care. However rifabutin may be omitted in HIV-infected patients on protease inhibitors because of significant interactions (Table 19). 

A. One-week triple therapy regimes combining a proton pump inhibitor with two antibiotics chosen from amoxicillin, clarithromycin and metronidazole are effective in about 90% of cases. 

F. Bismuth based regimes, as part of dual or triple therapy are also effective. 

Akerele EO, Levin F, Nunes E, Brady R Kleber H (2002). Effects of HIV triple therapy on methadone levels. American Journal on Addictions, 11, 308-14... 

BFM and St. Jude protocols, are that on BFM protocols no topoisomerase 11 inhibitors are given in close association with thiopurines and, finally, that on BFM protocols no intrathecal triple therapy (methotrexate, cytarabine, and a glucocorticoid) are given concurrent with cranial radiotherapy and 6-MP. Another important toxicity issue associated with TPMT status relates to the above-described VOD-like symptoms of the liver in childhood ALL patients treated with 6-TG on the British MRC ALL97 trial (209). In this trial, TPMT activity was significantly lower in children in whom VOD developed while no differences in RBC 6-TGN levels were described. This information in association with ongoing research efforts will help to develop a better understanding of 6-TG-associated liver toxicity and may help to identify those individuals upfront who should not be administered 6-TG. 

Traditional long-term anti-ischaemic triple therapy for coronary artery disease consists of a long-acting nitrate, p-adrenoceptor antagonist and a calcium-entry blocker. Most of these agents are also used for the treatment of hypertension. 

Use of these as part of triple therapy for eradication of Campylobacter pylori has been almost completely supplanted by antacid and antibiotic treatment. 

Finally, it is universally accepted at present that Helicobacter pylori infection has a definitive ethiological role in peptic ulcer disease, and that erradication therapy is warranted in these clinical scenarios. The majority of therapeutic trials have included the application of triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxycillin or metronidazol and is to date the treatment of choice. However, recent studies have reported antibiotic resistance which can be one reason for failure of treatment of Helicobacter pylori infection [101-103], and new treatment strategies are therefore Wellcome. Flavonoids, in addition to their gastroprotective activity previously commented, have been also shown to inhibit Helicobacter pylori growth in vitro. In this way, Beil et al. [50]... 

Treatment of H. pylori infection typically consists of a combination therapy, using several drugs simultaneously.42 For example, one common form of triple therapy consists of two antibacterials (amoxicillin and clarithromycin) and one of the PPIs described earlier in this chapter.17 36 Alternatively, various quadruple therapies have been used combining bismuth compound (described later in the section on Treatment of Diarrhea ) with a PPI and two antibacterials (e.g., tetracycline and metronidazole).5,36 These drug regimens are typically administered for 1 to 2 weeks and... 

For the eradication of Helicobacter pylori in peptic ulceration, omeprazole may be combined with antibacterials in dual or triple therapy. Effective triple therapy regimens include omeprazole 20 mg twice daily combined with amoxycillin 500 mg and metronidazole 400 mg, both three times daily clarithromycin 500 mg and metronidazole 40 mg (or tinidazole 500 mg) both twice daily or with amoxycillin 1 g and clarithromycin 500 mg both twice daily. These regimens are given for 1 week. Dual therapy regimens, such as omeprazole 40 mg daily with either amoxycillin 750 mg to 1 g twice daily or clarithromycin 500 mg three times daily, are less effective and must be given for 2 weeks. Omeprazole alone may be continued for a further 4r-8 weeks [1]. 

When added to methotrexate background therapy, cyclosporine, chloroquine, leflunomide, infliximab, adalimumab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. A triple-therapy regimen (methotrexate, sulfasalazine, and hydroxychloroquine) was recently tested and compared with methotrexate plus sulfasalazine or methotrexate plus hydroxychloroquine. Seventy-eight percent of the triple therapy group achieved an ACR20 response at 2 years, compared with 60% of those treated with methotrexate plus hydroxychloroquine and 49% of those treated with methotrexate plus sulfasalazine. 

The randomized controlled clinical trials performed by Freis and his colleagues at the Veterans Administration Hospitals have provided some of the first solid evidence that moderate permanent hypertension has an improved prognosis when actively treated by sodium depletion (hydrochlorothiazide), by interruption of the sympathetic nervous system (reserpine) and with a vasodilator (hydralazine) (262). In parallel, the beneficial effects of this triple therapy were demonstrated in spontaneously hypertensive rats by the spectacular prevention and cure of their cardiac, vascular, and renal lesions (263). 

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