One concern is that bevacizumab will interfere with these normal processes, and worsen conditions like coronary artery disease or peripheral artery disease.The main side effects are hypertension and heightened risk of bleeding. Bowel perforation has been reported. Fatigue and infection are also common. In advanced lung cancer, less than half of patients qualify for treatment. Nasal septum perforation and renal thrombotic microangiopathy have been reported. In December 2010, the FDA warned of the risk of developing perforations in the body, including in the nose, stomach, and intestines. In 2013, Hoffmann-La Roche announced that the drug was associated with 52 cases of necrotizing fasciitis from 1997 to 2012, of which 17 patients died. About 2/3 of cases involved patients with colorectal cancer, or patients with gastrointestinal perforations or fistulas. These effects are largely avoided in ophthalmological use since the drug is introduced directly into the eye thus minimizing any effects on the rest of the body.Neurological adverse events include reversible posterior encephalopathy syndrome. Ischemic and hemorrhagic strokes are also possible.Protein in the urine occurs in approximately 20% of people. This does not require permanent discontinuation of the drug. Nonetheless, the presence of nephrotic syndrome necessitates permanent discontinuation of bevacizumab. Mechanism of action
Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A). VEGF-A is a growth factor protein that stimulates angiogenesis in a variety of diseases, especially in cancer. Bevacizumab is the first available angiogenesis inhibitor in the United States.
Some of the paleospinothalamic fibers peel off in the brain stem, connecting with the reticular formation or midbrain periaqueductal gray, and the remainder terminate in the intralaminar nuclei of the thalamus.Pain-related activity in the thalamus spreads to the insular cortex (thought to embody, among other things, the feeling that distinguishes pain from other homeostatic emotions such as itch and nausea) and anterior cingulate cortex (thought to embody, among other things, the affective/motivational element, the unpleasantness of pain), and pain that is distinctly located also activates primary and secondary somatosensory cortex.Spinal cord fibers dedicated to carrying A-delta fiber pain signals, and others that carry both A-delta and C fiber pain signals to the thalamus have been identified. Other spinal cord fibers, known as wide dynamic range neurons, respond to A-delta and C fibers, but also to the much larger, more heavily myelinated A-beta fibers that carry touch, pressure and vibration signals. Ronald Melzack and Patrick Wall introduced their gate control theory in the 1965 Science article "Pain Mechanisms: A New Theory". The authors proposed that the thin C and A-delta (pain) and large diameter A-beta (touch, pressure, vibration) nerve fibers carry information from the site of injury to two destinations in the dorsal horn of the spinal cord, and that A-beta fiber signals acting on inhibitory cells in the dorsal horn can reduce the intensity of pain signals sent to the brain.