Pessaries require a provider to fit the device, but most can be removed, cleaned, and replaced by the woman herself. Pessaries should be offered to women considering surgery as a non-surgical alternative. Surgery
With surgery (for example native tissue repair, biological graft repair, absorbable and non-absorbable mesh repair, colpopexy, colpocleisis). Surgery is used to treat symptoms such as bowel or urinary problems, pain, or a prolapse sensation. Evidence does not support the use of transvaginal surgical mesh compared with native tissue repair for anterior compartment prolapse owing to increased morbidity. For posterior vaginal repair, the use of mesh or graft material does not seem to provide any benefits. Safety and efficacy of many newer meshes is unknown. The use of a transvaginal mesh in treating vaginal prolapses is associated with side effects including pain, infection, and organ perforation. Transvaginal repair seems to be more effective than transanal repair in posterior wall prolapse, but adverse effects cannot be excluded. According to the FDA, serious complications are "not rare." A number of class action lawsuits have been filed and settled against several manufacturers of TVM devices.Compared to native tissue repair, transvaginal permanent mesh probably reduces womens perception of vaginal prolapse sensation and probably reduces the risk of recurrent prolapse and of having repeat surgery for prolapse. On the other hand, transvaginal mesh probably has a greater risk of bladder injury and of needing repeat surgery for stress urinary incontinence or mesh exposure.
Mechanism of action
The mechanism seems to vary with different organisms and is not well understood. However, pentamidine is suspected to work through various methods of interference of critical functions in DNA, RNA, phospholipid and protein synthesis. Pentamidine binds to adenine-thymine-rich regions of the Trypanosoma parasite DNA, forming a cross-link between two adenines four to five base pairs apart. The drug also inhibits topoisomerase enzymes in the mitochondria of Pneumocystis jirovecii. Similarly, pentamidine inhibits type II topoisomerase in the mitochondria of the Trypanosoma parasite, resulting in a broken and unreadable mitochondrial genome. Resistance
Strains of the Trypanosoma brucei parasite that are resistant to pentamidine have been discovered. Pentamidine is brought into the mitochondria through carrier proteins, and the absence of these carriers prevents the drug from reaching its site of action. Pharmacokinetics
Absorption: Pentamidine is completely absorbed when given intravenously or intramuscularly. When inhaled through a nebulizer, pentamidine accumulates in the bronchoalveolar fluid of the lungs at a higher concentration compared to injections. The inhaled form is minimally absorbed in the blood. Absorption is unreliable when given orally.Distribution: When injected, pentamidine binds to tissues and proteins in the plasma. It accumulates in the kidney, liver, lungs, pancreas, spleen, and adrenal glands. Additionally, pentamidine does not reach curative levels in the cerebrospinal fluid. It has a volume of distribution of 286-1356 liters when given intravenously and 1658-3790 liters when given intramuscularly. Inhaled pentamidine is mainly deposited into the bronchoalveolar lavage fluid of the lungs.Metabolism: Pentamidine is primarily metabolized by Cytochrome P450 enzymes in the liver.