Oncology
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
The primary approach to treatment of acute leukemias is combination drug therapy. Bone marrow traosplantation is becoming increasingly utilized for treatment of both ALL and ANLL. The procedure requires total body irradiation, often with high-dose drug therapy to destroy residual leukemia cells and produce irreversible bone marrow suppression. The bone marrow for transplant is obtained from a human lymphocyte antigen (HLA)-matched donor (allogenetic), an identical twin (syngenetic), or from the patient in remission (autologous). Complications include failure to engraft, infection from immunosuppression, and graft-versus-host disease (GVHD). Plasma cell disorders (PCD) involve production of excessive amounts of an immunoglobulin, such as in multiple myeloma.
Toward Clinical Pharmacologic Otoprotection
Stavros Hatzopoulos, Andrea Ciorba, Mark Krumm in Advances in Audiology and Hearing Science, 2020
Preclinical studies have also evaluated protection via combinations of agents that include NAC and other agents. Studies assessing combinations of agents frequently lack single-agent controls. Thus, it has been difficult to determine if there was any added benefit of the combined agents relative to either single agent for combinations of NAC and salicylate (Kopke et al., 2000; Coleman et al., 2010), NAC and the Src-PTK inhibitor KX1-004 (Bielefeld et al., 2011), NAC and 4-OHPBN (Choi et al., 2008; Choi et al., 2014a), or NAC, 4-OHBPN, and acetyl-L-carnitine (ALCAR) [see Choi et al. (2008); Choi et al. (2011)]. Although the combination-drug literature shows significant protection, the mechanism of action and relative contribution of each agent to the overall combined drug effect is unclear.
Hypertension
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
When the initial systolic BP is higher than 160 mm Hg, regardless of lifestyle factors, two drugs are indicated in the proper dose and combination. There are many single-tablet combination drugs, which are preferred because they make it easier for patients to adhere. Often, four or more drugs are required for resistant hypertension that is not reduced with three different antihypertensives. Several changes in medications are often needed to achieve enough BP control. Since lifelong treatment is often needed, insufficient patient adherence can interfere with treatment success. It is important to offer patients empathy about their conditions, and support their needs while educating them. Table 7.2 summaries medications that are used for the initial management of hypertension.
Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Xueqin Huang, Li You, Eugenie Nepovimova, Miroslav Psotka, David Malinak, Marian Valko, Ladislav Sivak, Jan Korabecny, Zbynek Heger, Vojtech Adam, Qinghua Wu, Kamil Kuca
Capivasertib is a potent oral ATP-competitive inhibitor developed by AstraZeneca that can effectively inhibit all isoforms of AKT. Capivasertib has a limited single-agent effect, but it is more effective when combined with traditional chemotherapy, and can be used as a sensitiser for tumour chemotherapy272. Several trials have confirmed the effectiveness of combination drugs. Capivasertib has shown promising efficacy in breast cancer and has significant activity against AKT1-E17K-mutated cancers. The median PFS of TNBC patients receiving treatment with capivasertib and paclitaxel was 5.9 months. In PIK3CA/AKT1/PTEN-altered tumours, this regimen was significantly beneficial, with a median PFS of 9.3 months273. When capivasertib was coupled with fulvestrant in patients with resistant breast cancer, the capivasertib group considerably surpassed the placebo group in terms of median PFS (10.3 months and 4.8 months, respectively). As a result, a relevant phase III trial is planned274. Furthermore, AKT signalling overexpression causes radioresistance in oral squamous cell carcinoma (OSCC) cells, and capivasertib encapsulated in new nanoparticles can sensitise radioresistant OSCC cells to IR275. Therefore, combining Capivasertib with nanoparticles is an effective strategy for treating OSCC patients. Currently, research on the combination therapy of Capivasertib is ongoing.
An in-depth analysis of novel combinatorial drug therapy via nanocarriers against HIV/AIDS infection and their clinical perspectives: a systematic review
Published in Expert Opinion on Drug Delivery, 2021
Abdul Muheem, Sanjula Baboota, Javed Ali
Combination drugs are the standard of practice for HIV infection [18]. However, the combinatorial antiretroviral loaded nanocarrier approach shows promising results for the management of HIV infection. It possesses several advantages, including controlled pharmacokinetics of each drug, improved therapeutic efficacy by synergistic effect, minimized adverse drug reactions [19], reduced toxicity, reduced emergence of viral resistance [20]. However, the physicochemical properties of antiretroviral drugs (ARDs) may inhibit their co-formulation in traditional dosage forms [21]. A strategic approach for selecting co-formulating drugs is required and engineering the nano delivery of these combinatorial drugs to have significant inhibitory action against both cell-free and cell-to-cell virus transmission [22,23]. Thus, the development of the delivery system that fabricates more than two drugs into a single dosage possesses the potential to improve the therapeutic efficacy of current ART. This approach could be a successful novel delivery platform for the management of HIV infection.
The status surrounding chloroquine and other drugs as potential anti-infective agents for COVID-19
Published in Expert Review of Respiratory Medicine, 2020
Dindial Ramotar
esides anti-malarial drugs, several other treatments are being evaluated in order to make recommendations for COVID-19 patients. These include using combinations of HIV antivirals such as lopinavir and ritonavir, or other antivirals such as remdesivir, together with interferon [3,10]. Other single or combination drugs proposed to be tested include ribavirin, oseltamivir as well as inhibitors to block the angiotensin receptor to prevent docking of the SARS-CoV-2 S-protein [3]. With the vast array of clinical trials, over 450 being conducted globally, there will be promising drug combinations and gene therapy that will prevent SARS-CoV-2 infection if not spare the life of the affected patients. It is noteworthy that gene therapy takes advantage of using the adeno-associated virus for rapid and targeted delivery of specific antibody against SARS-CoV-2 in the upper airways, whereby the antibody could mount a response within a week and the protection can last for nearly a year. Of particular note, passive immunization with convalescent blood plasma from COVID-19 patients who recovered and harbor a spectrum of polyclonal and monoclonal antibodies against the virus can provide short-term immunity [3].
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