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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Antimetabolites include methotrexate and 5-FU. Methotrexate, a folic acid antagonist, is indicated for use in the treatment of many cancers, including breast cancer, head and neck cancer, acute lymphocytic leukemia, NHL, bladder cancer, colorectal cancer, and gestational trophoblastic disease. It is an abortifacient and should not be given at any time during pregnancy. When given in the first trimester, this class of agents is associated with a constellation of severe fetal anomalies known as “aminopterin syndrome.” The syndrome includes growth deficiency, patent cranial sutures, craniosynostosis, unusual skull shapes, dysmorphic facies, hydrocephalus, mental retardation, and skeletal defects (35).
Alternative Tumor-Targeting Strategies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
One of the greatest challenges in the discovery and development of new therapeutic agents and strategies for the treatment of cancer is the achievement of selectivity between tumor cells and healthy tissues. With few exceptions, all small-molecule and biological agents, including antibody-based therapies (see Chapters 9 and 7, respectively) and other types of therapies (e.g., radiotherapy), in clinical use today are associated with varying degrees of side effects (i.e., toxicities or adverse drug reactions [ADRs]) due to their collateral action on healthy cells and tissues (Figure 10.1A). The classic chemotherapy agents (i.e., the antimetabolites, anti-tubulin agents, and DNA-interactive agents described in Chapters 3–5) have the least selectivity, and their effect on healthy tissues, such as the lining of the GI tract and hair follicles, gives rise to problematic side effects such as nausea, vomiting, alopecia, and fatigue. Newer generations of small-molecule molecularly targeted agents such as the kinase inhibitors (see Chapter 6) are designed to be much more selective, targeting mutated proteins and aberrant signaling pathways that are sometimes unique to the tumor cells, thereby sparing healthy cells and leading to a lower level of side effects. Endocrine therapies (Chapter 8) can also be very selective with a low level of side effects; however, these therapies are limited to a small number of tumor types which are hormone sensitive (e.g., breast, prostate, and neuroendocrine).
Antineoplastic Agents
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Antimetabolites alter normal cellular functions by substituting for components within key metabolic processes. An agent may be incorporated as a substrate or may inhibit the normal functioning of an enzyme. The net effect of interference with cellular biochemical reactions is disruption of nucleic acid synthesis. Thus, antimetabolites are effective on rapidly proliferating cells, mostly during the S phase (DNA synthesis phase) of nucleic acid synthesis. Consequently, they are indicated for the induction and maintenance of remission of leukemias, metastatic breast cancer, and colon, rectal, stomach, and pancreatic carcinomas. Antimetabolites, alone and in combination, are also used in the management of other proliferative disorders such as psoriasis and rheumatoid arthritis (methotrexate).
Differences in the Surgical Outcomes of Glaucoma Surgery in Patients of African Caribbean Descent
Published in Current Eye Research, 2022
A. M. Nagar, P. Maghsoudlou, R. Wormald, K. Barton, P. Hysi, K. S. Lim
Surgical success and failure are defined differently across studies, and means that direct comparison is often challenging. However, regardless of definition, surgical outcomes following trabeculectomy, including IOP reduction, rates of failure and reoperation rates in ACD, are poorer than ED (Table 3). This is especially highlighted in studies where antimetabolites are not used. NPFS provide an alternative surgical approach for this cohort of patients, but more studies are required to assess if they can be considered as a primary approach in ACD. A systematic review that compared outcomes of trabeculectomy and canaloplasty in studies with a primarily ED population showed that trabeculectomy was more effective in lowering IOP but had more bleb-related complications.89 Canaloplasty did not appear inferior in terms of success rate or the number of post-operative anti-glaucoma medications, suggesting a potential appropriate alternative in a population that may have reduced access to follow-up.
Systemic Immunosuppression in Cornea and Ocular Surface Disorders: A Ready Reckoner for Ophthalmologists
Published in Seminars in Ophthalmology, 2022
Antimetabolites act by inhibition of nucleic acid synthesis, thereby inhibiting cell proliferation.13 Azathioprine is a purine nucleoside, which suppresses the synthesis of inosinic acid, thereby interfering with the DNA replication and RNA transcription.4 The percentage of patients achieving corticosteroid-sparing success following azathioprine use is reported to be lower than other antimetabolites.14–17 Other disadvantages include a higher discontinuation rate due to gastrointestinal intolerance, bone marrow suppression and hepatotoxicity.1,4,11 However, bone marrow suppression is uncommon at low doses, and as such, is reversible. The recommended dose for azathioprine is 1–3 mg/kg/day (maximum recommended dose is 2.5 mg/kg/day).4 A complete blood count (CBC) should be performed every month and liver function tests (LFTs) should be performed every 3 months. If liver enzyme levels are >1.5 times the upper limit of normal, the dose should be decreased by 25–50 mg/day and the repeat LFTs done in 2 weeks.4
Differential Effects of TGF-β2 on the Low-Density Lipoprotein Receptor Expression in Three Types of Human Subconjunctival Fibroblasts
Published in Current Eye Research, 2021
Jiajian Wang, Chao Jiang, Qinghe Jing, Yongxiang Jiang, Tingting Shao
Antimetabolites (such as mitomycin, fluorouracil, etc.) are now used after glaucoma surgery to reduce the formation of postoperative scars. However, these drugs reach all cells and can inhibit or even kill normal cells as well as abnormal proliferating cells, which may lead to various serious complications and increase the incidence of severe events such as filtering bleb leaks, low intraocular pressure, cataracts, severe visual impairment, filtering bleb infection, and endophthalmitis.15–17 Therefore, it is particularly important to develop a strategy to selectively deliver antimetabolites to abnormally proliferating cells and reduce the drug toxicity and side effects. We hope to find a drug target that can specifically deliver antimetabolites to abnormally proliferating fibroblasts in subconjunctival tissues and effectively and accurately inhibit scar formation in the filtering bleb area after glaucoma surgery.