Studies have suggested cocaethylene is more euphoric, and has a higher cardiovascular toxicity than cocaine by itself.Depending on liver and kidney function, cocaine metabolites are detectable in urine. Benzoylecgonine can be detected in urine within four hours after cocaine intake and remains detectable in concentrations greater than 150 ng/mL typically for up to eight days after cocaine is used. Detection of cocaine metabolites in hair is possible in regular users until after the sections of hair grown during the period of cocaine use are cut or fall out. Pharmacodynamics
The pharmacodynamics of cocaine involve the complex relationships of neurotransmitters (inhibiting monoamine uptake in rats with ratios of about: serotonin:dopamine = 2:3, serotonin:norepinephrine = 2:5). The most extensively studied effect of cocaine on the central nervous system is the blockade of the dopamine transporter protein. Dopamine neurotransmitter released during neural signaling is normally recycled via the transporter; i.e., the transporter binds the transmitter and pumps it out of the synaptic cleft back into the presynaptic neuron, where it is taken up into storage vesicles. Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporters function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the synaptic cleft. The increased concentration of dopamine in the synapse activates post-synaptic dopamine receptors, which makes the drug rewarding and promotes the compulsive use of cocaine.Cocaine affects certain serotonin (5-HT) receptors; in particular, it has been shown to antagonize the 5-HT3 receptor, which is a ligand-gated ion channel.
On average, about 2.8 colonscopies are necessary to achieve control of disease. The majority of cases may be managed with colonoscopy alone. Narrow-band imaging, an imaging technique used to enhance features of mucosa seen during colonoscopy, may improve detection of serrated lesions; however, one multicenter trial did not show improved detection.If polyps are very numerous, very large, or their growth cannot be controlled with colonoscopy, then surgery may be necessary. When surgery is necessary, a total abdominal colectomy with ileorectal anastomosis should be considered to minimize the risk of colon cancer. If surgery is necessary and involvement of polyps is focal or largely confined to a particular section of bowel, then segmental resection may be considered. Segmental resection is also recommended for cancer. In most cases, the rectum is left in place. Any remaining segments of colon or rectum require annual surveillance with colonoscopy.First degree relatives of people with SPS are at a higher risk of colorectal cancer and SPS. As such, these individuals should undergo screening with colonoscopy beginning at the earliest of the following: 40 years of age, the age of the youngest diagnosis of SPS in the family, or 10 years younger than the earliest CRC related to SPS. Repeat colonoscopy should be performed at 5 year intervals. Prognosis
The overall risk of colorectal cancer is about 19.9%. However, the risk of cancer varies widely and depends on age, polyp burden, phenotype and the presence of dysplasia on histology. Endoscopic surveillance can decrease the risk of progression to cancer.