Symptoms may be exacerbated with prolonged sitting, prolonged standing, alcohol, heat, exercise, or eating a large meal.Up to one-third of POTS patients experience fainting for many reasons, including but not limited to standing, physical exertion, or heat exposure. POTS patients may also experience orthostatic headaches. Some POTS patients may develop blood pooling in the extremities, characterized by a reddish-purple color of the legs and/or hands upon standing. 48% of people with POTS report chronic fatigue and 32% report sleep disturbances. Other POTS patients only exhibit the cardinal symptom of orthostatic tachycardia. Additional signs and symptoms are varied, and may include excessive sweating, lack of sweating, heat intolerance, digestive issues such as nausea, indigestion, constipation, and diarrhea, post-exertional malaise, coat-hanger pain, brain fog, and syncope or presyncope. Brain fog
One of the most disabling and prevalent symptoms in POTS is "brain fog", a term used by patients to describe the cognitive difficulties they experience. In one survey of 138 POTS patients, brain fog was defined as "forgetful" (91%), "difficulty thinking" (89%), and "difficulty focusing" (88%). Other common description was "Difficulty processing what others say" (80%), Confusion (71%), Lost (64%), and "Thoughts moving too quickly" (40%).
Temozolomide is a prodrug; it is spontaneously hydrolyzed at physiological pH to 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC), which further splits into monomethylhydrazine, likely the active methylating agent, and 5-aminoimidazole-4-carboxamide (AIC). Other metabolites include temozolomide acid and unidentified hydrophilic substances.Plasma half-life is 1.8 hours. The substance and its metabolites are mainly excreted via the urine. Chemical properties
Temozolomide is an imidazotetrazine derivative. It is slightly soluble in water and aqueous acids, and decomposes at 212 °C (414 °F). It was recently discovered that temozolomide is an explosive, tentatively assigned as UN Class 1.Mirroring its medicinal use as an alkylating antineoplastic agent, temozolomide has been reported to be a comparatively safe and stable in situ source of diazomethane in organic synthesis. In particular, its use as a methylating and cyclopropanating reagent was demonstrated. History
The agent was discovered by Simon Langdon, Niel Gibson and John Hickman at Aston University in Birmingham, England. The molecule was synthesised by PhD student Robert Stone, in a project directed by Malcolm Stevens to find anti-allergens. Its preclinical activity was reported in 1987 in Cancer Research. Stevens then directed its development with the late Edward Newlands at Charing Cross Hospital.It was approved for medical use in the European Union in January 1999, and in the United States in August 1999. The intravenous formulation was approved in the United States in February 2009. Research
Laboratory studies and clinical trials have started investigating the possibility of increasing the anticancer potency of temozolomide by combining it with other pharmacologic agents.