It does so in a time-dependent rather than dose-dependent manner, meaning that risk can be minimized by reducing the duration of use.Amikacin causes nephrotoxicity (damage to the kidneys), by acting on the proximal renal tubules. It easily ionizes to a cation and binds to the anionic sites of the epithelial cells of the proximal tubule as part of receptor-mediated pinocytosis. The concentration of amikacin in the renal cortex becomes ten times that of amikacin in the plasma; it then most likely interferes with the metabolism of phospholipids in the lysosomes, which causes lytic enzymes to leak into the cytoplasm. Nephrotoxicity results in increased serum creatinine, blood urea nitrogen, red blood cells, and white blood cells, as well as albuminuria (increased output of albumin in the urine), glycosuria (excretion of glucose into the urine), decreased urine specific gravity, and oliguria (decrease in overall urine output). It can also cause urinary casts to appear. The changes in renal tubular function also change the electrolyte levels and acid-base balance in the body, which can lead to hypokalemia and acidosis or alkalosis. Nephrotoxicity is more common in those with pre-existing hypokalemia, hypocalcemia, hypomagnesemia, acidosis, low glomerular filtration rate, diabetes mellitus, dehydration, fever, and sepsis, as well as those taking antiprostaglandins.
Lifitegrast, sold under the brand name Xiidra (), is a medication for the treatment of signs and symptoms of dry eye, a syndrome called keratoconjunctivitis sicca. Lifitegrast reduces inflammation by inhibiting inflammatory cell binding. It is often used in conjunction with ciclosporin (Ikervis, Restasis, or Cequa) for dry eye treatment including meibomian gland dysfunction and inflammatory dry eye. Adverse effects
Common side effects in clinical trials were eye irritation, discomfort, blurred vision, and dysgeusia (a distortion of the sense of taste). Pharmacology
Lifitegrast is supplied as an eye drop. Mechanism of action
Lifitegrast inhibits an integrin, lymphocyte function-associated antigen 1 (LFA-1), from binding to intercellular adhesion molecule 1 (ICAM-1). This mechanism down-regulates inflammation mediated by T lymphocytes. History
Lifitegrast was initially designed and developed by SARcode Bioscience which was acquired by Shire in 2013, which submitted a new drug application to the US Food and Drug Administration (FDA) in March 2015. The FDA granted Shire a priority review a month later, and requested additional clinical data, which were supplied in January 2016; approval was granted on 11 July 2016. Lifitegrast was approved by Health Canada in January 2018, and available in Canadian pharmacies as of March 2018. Shire was acquired by Takeda Pharmaceutical Company in late 2018. In May 2019 Novartis reached an agreement to purchase the assets associated with Lifitegrast. Novartis will pay Takeda an upfront payment of $3.4 billion, while the latter drugmaker is eligible for milestone payments of as much as $1.9 billion. Novartis noted that the drug amassed approximately $400 million in revenue in 2018.