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Investigators and Investigations
Published in Mickey C. Smith, E.M. (Mick) Kolassa, Walter Steven Pray, Government, Big Pharma, and the People, 2020
Mickey C. Smith, E.M. (Mick) Kolassa, Walter Steven Pray
Fixed combination Drugs are products with two or more active ingredients in “fixed” proportions. A very old example would be the product from the 1950s, Milprem, which combined meprobamate with Premarin (conjugated estrogen). The logic of that product was rather sound for use in menopause – the estrogen the body needs and the minor tranquilizer that conventional wisdom says every menopausal woman needs.
Antiepileptic Drugs in Children
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
W. Edwin Dodson, James D. Reggin
VPA in monotherapy is relatively nontoxic. In combination drug therapy, drug interactions contribute to a significantly higher incidence of toxicity. Rapid extensive fluctuations of VPA can produce transient toxicity directly or by displacing PHT or CBZ from serum proteins. Occasionally, children have adverse behavioral reactions to VPA, but in contrast to PB-induced adverse behavioral effects, these usually subside. The major dose-related neurotoxicity in children consists of sedation and incoordination; adverse gastrointestinal effects and troublesome weight gain are less problematic in children than adults. Dose-related thrombocytopenia is an occasional problem that necessitates dosage reduction.
Oncology
Published in Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss, Understanding Medical Terms, 2020
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss
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.
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.
Research progress of p38 as a new therapeutic target against morphine tolerance and the current status of therapy of morphine tolerance
Published in Journal of Drug Targeting, 2023
As a highly effective painkiller, morphine is widely used in the clinic. In recent years, there are more and more adverse reactions caused by morphine, even morphine tolerance, which has caused great trouble to clinicians. There are a lot of studies on morphine tolerance, but the research on morphine tolerance is still insufficient because of its complex neural mechanism. There are many mechanisms that affect morphine tolerance, but the influencing factors and therapeutic drugs found in current studies are lack of specificity. In recent years, the p38MAPK of the MAPK family plays a central role in the inhibition of morphine tolerance. Inhibition of p38MAPK can reduce morphine tolerance and prolong morphine action time. Generally speaking, most of the drugs to improve morphine tolerance play a pharmacological role around p38MAPK, which reduces morphine tolerance to a great extent. Although the preventive effect is good, the dose of long-term combination drugs in vivo and the possible adverse reactions are unknown. There is a wide range of drugs used in the clinic, and there is a lack of targeted drugs to treat morphine tolerance. at present, there is no clear drug that can reverse morphine tolerance, and there is a lack of pharmacological research on administration reversal therapy after the establishment of the morphine tolerance model. Therefore, the follow-up study of morphine tolerance can focus on targeted inhibition of specific targets in the p38MAPK pathway and reversal of morphine tolerance.
Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics for the treatment of psoriasis
Published in Expert Opinion on Drug Delivery, 2021
The conventional topical anti-psoriatic formulations offer considerable shortcomings of limited drug transport through the skin, unsuitable long-term use along with severe toxicity. An in-depth understanding of psoriasis pathology, as well as the consequences of the present therapeutic regimen, led newer nanocarriers like SLNs and NLCs to come to the scenario. These drug delivery systems pose several benefits like higher drug concentration at the disease site, subsequently lowering the dosing frequency, systemic absorption, and hence side-effects [93]. Though initially, the research findings were confined only to single therapeutic agents, still now there is no such perfect single topical agent has been found which can completely cure psoriasis. This is when the idea of combinational therapy emerged in the field of psoriasis management. Nevertheless, in most cases, the administration of combination drugs needs to compromise with patient compliance and as a result, the need for a single carrier to deliver both the drugs originated [94]. Consequently, several SLNs and NLCs are being investigated for assessing their ability to carry dual drugs and alleviate psoriasis. The following sections briefly describe the different anti-psoriatic single and dual drug-loaded SLNs and NLCs that have been developed in the past few years.