Removal of the colon and rectum generally cures the condition.Together with Crohns disease, about 11.2 million people were affected as of 2015. Each year it newly occurs in 1 to 20 per 100,000 people, and 5 to 500 per 100,000 individuals are affected. The disease is more common in North America and Europe than other regions. Often it begins in people aged 15 to 30 years, or among those over 60. Males and females appear to be affected in equal proportions. It has also become more common since the 1950s. Together, ulcerative colitis and Crohns disease affect about a million people in the United States. With appropriate treatment the risk of death appears the same as that of the general population. The first description of ulcerative colitis occurred around the 1850s. Signs and symptoms
Gastrointestinal
People with ulcerative colitis usually present with diarrhea mixed with blood, of gradual onset that persists for an extended period of time (weeks). Additional symptoms may include fecal incontinence, increased frequency of bowel movements, mucus discharge, and nocturnal defecations. With proctitis (inflammation of the rectum), people with UC may experience urgency or rectal tenesmus, which is the urgent desire to evacuate the bowels but with the passage of little stool. Tenesmus may be misinterpreted as constipation, due to the urge to defecate despite small volume of stool passage. Bloody diarrhea and abdominal pain may be more prominent features in severe disease. The severity of abdominal pain with UC varies from mild discomfort to very painful bowel movements and abdominal cramping.
Similar concern is appropriate when it is used with sedating medications.Guanfacine is known to lower the users tolerance for alcohol, heightening its effect, and alcohol use may prolong the effects of the medication. Pharmacology
Guanfacine is a highly selective agonist of the α2A adrenergic receptor, with low affinity for other receptors. However it may also be a potent 5-HT2B receptor agonist, which can be associated with valvulopathy, although not all 5-HT2B agonists have this effect. Mechanism of action
Guanfacine works by activating α2A adrenoceptors within the central nervous system. This leads to reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone, which lowers both systolic and diastolic blood pressure.In ADHD, guanfacine works by strengthening regulation of attention and behavior by the prefrontal cortex. These enhancing effects on prefrontal cortical functions are believed to be due to drug stimulation of post-synaptic α2A adrenoceptors on dendritic spines. cAMP-mediated opening of HCN and KCNQ channels is inhibited, which enhances prefrontal cortical synaptic connectivity and neuronal firing. The use of guanfacine for treating prefrontal disorders was developed by the Arnsten Lab at Yale University. Pharmacokinetics
Guanfacine has an oral bioavailability of 80%. There is no clear evidence of any first-pass metabolism. Elimination half-life is 17 hours with the major elimination route being renal. The principal metabolite is the 3-hydroxy-derivative, with evidence of moderate biotransformation, and the key intermediate is an epoxide. Elimination is not impacted with impaired renal function.