Aflibercept, sold under the brand names Eylea and Zaltrap, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals and is approved in the United States and the European Union.It is an inhibitor of vascular endothelial growth factor (VEGF). Medical uses
It is used for the treatment of wet macular degeneration and is administered as an intravitreal injection, that is, into the eye. For cancer treatment, is given intravenously in combination with the other cancer drugs 5-fluorouracil and irinotecan and the adjuvant folinic acid.On 27 August 2014, Eylea was also indicated for the treatment of people with visual impairment due to diabetic macular oedema, according to the updated summary of product characteristics. In May 2019 FDA expanded the indication for aflibercept to include all stages of diabetic retinopathy. Contraindications
Eylea is contraindicated in patients with infections or active inflammations of or near the eye, while Zaltrap has no contraindications. Adverse effects
Common adverse effects of the eye formulation include conjunctival hemorrhage, eye pain, cataract, vitreous detachment, floaters, and ocular hypertension.Zaltrap has adverse effects typical of anti-cancer drugs, such as reduced blood cell count (leukopenia, neutropenia, thrombocytopenia), gastrointestinal disorders like diarrhoea and abdominal pain, and fatigue. Another common effect is hypertension (increased blood pressure). Interactions
No interactions are described for either formulation. Mechanism of action
In wet macular degeneration, abnormal blood vessels grow in the choriocapillaris, a layer of capillaries in the eye, leading to blood and protein leakage below the macula.
The risk of bipolar disorder is nearly ten-fold higher in first-degree relatives of those with bipolar disorder than in the general population; similarly, the risk of major depressive disorder is three times higher in relatives of those with bipolar disorder than in the general population.Although the first genetic linkage finding for mania was in 1969, linkage studies have been inconsistent. Findings point strongly to heterogeneity, with different genes implicated in different families. Robust and replicable genome-wide significant associations showed several common single-nucleotide polymorphisms (SNPs) are associated with bipolar disorder, including variants within the genes CACNA1C, ODZ4, and NCAN. The largest and most recent genome-wide association study failed to find any locus that exerts a large effect, reinforcing the idea that no single gene is responsible for bipolar disorder in most cases. Polymorphisms in BDNF, DRD4, DAO, and TPH1 have been frequently associated with bipolar disorder and were initially associated in a meta-analysis, but this association disappeared after correction for multiple testing. On the other hand, two polymorphisms in TPH2 were identified as being associated with bipolar disorder.Due to the inconsistent findings in a genome-wide association study, multiple studies have undertaken the approach of analyzing SNPs in biological pathways. Signaling pathways traditionally associated with bipolar disorder that have been supported by these studies include corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, Phospholipase C signaling, glutamate receptor signaling, cardiac hypertrophy signaling, Wnt signaling, Notch signaling, and endothelin 1 signaling.