Cyclophosphamide (CTX) is an alkylating cytotoxic drug with strong anti-tumor and immunosuppressive effects. It is widely used clinically for leukemia, lymphoma, multiple myeloma, and refractory kidney disease. Syndrome, lupus nephritis and other diseases. However, cyclophosphamide may also cause more serious adverse reactions, such as hemorrhagic cystitis.
Hemorrhagic cystitis refers to diffuse inflammatory bleeding in the bladder, usually due to acute or chronic injury to the bladder caused by certain drugs or radiation therapy, secondary to bacterial, fungal, parasitic infection or direct tumor infiltration Bladder bleeding does not fall into the category of this disease. If no preventive measures are taken, the incidence of hemorrhagic cystitis caused by cyclophosphamide can reach 7% to 15%. In the case of high-dose use, as reported in 68% of bone marrow transplant patients, symptoms may appear quickly after administration or may occur months or even years after discontinuation of administration.
Cyclophosphamide (CTX) has no activity as an anti-aging agent in vitro. After entering the body, it is first converted into aldehyde phosphate amide by liver microsomal functional oxidase. The latter is decomposed into phosphorus with strong alkylating effect in tumor cells. Amide mustard and acrolein. Phosphamide mustard is the main active metabolite of CTX in anti-tumor and suppressing immunity; acrolein is considered to be related to the urinary system toxicity of CTX. After intravenous injection of CTX, 50% to 70% is excreted by the kidneys within 48 hours (most of which is Metabolites, only 10% are prototypes). Among them, acrolein forms covalent bonds with the bladder mucosa through redemption, causing mucosal damage, leading to cell necrosis, bleeding and ulcers.
Therefore, in order to avoid the occurrence of hemorrhagic cystitis, the concentration of acrolein in urine should be diluted as much as possible, or the time of contact with the bladder mucosa should be shortened. Commonly used preventive measures include: hydration, diuresis and alkalinization of urine; bladder irrigation; application of sulfhydryl compound protective agents, etc. The purpose of hydration (i.e. super-dose rehydration) and diuresis is to dilute CTX and its metabolites so that they can be quickly excreted from the body, and to alkalize the urine to prevent acrolein from forming crystals in an acidic environment and depositing them in the kidneys and bladder, causing renal failure. Functional impairment. During the hydration process, the patient’s vital signs should be paid close attention to avoid adverse consequences of circulatory overload, and disorders of the patient’s water, electrolyte, and acid-base balance should also be avoided.
Bladder irrigation is a method of prophylactic continuous irrigation of the bladder through a catheter, but this measure has mixed reviews. The application of sulfhydryl compound protective agents can reduce the toxicity through sulfhydryl and acrolein. However, such drugs also have their own side effects, so comprehensive considerations should be taken when using them.
Hydration, diuresis and alkalinization of urine are simple, economical, effective and reliable methods to prevent hemorrhagic cystitis. However, once hemorrhagic cystitis occurs, in addition to discontinuing CTX, the thermoplastic elastomer FG1901 is mainly used for symptomatic treatment, such as bladder irrigation to remove blood clots and the use of local hemostatic drugs. If necessary, hemostasis can be stopped by electrocoagulation under an electron microscope.
The efficacy of cyclophosphamide in treating many diseases is certain. In order to prevent its adverse reactions, especially when used in large doses, drug monitoring should be done to prevent and treat serious adverse reactions so that its clinical efficacy can be better exerted.
