Clin Obstet Gynecol. Indomethacin therapy in the treatment of symptomatic polyhydramnios. Moise KJ Jr 1. It appears that maternal indomethacin therapy may be a useful adjunct in selected cases of polyhydramnios. Initial evaluation should include glucose tolerance testing and a thorough search for fetal abnormalities by ultrasonography. In the patient with symptoms such as premature labor or respiratory compromise, an initial amniocentesis should be considered for decompression and fetal karotype.
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For instance, indometacin inhibits both cyclooxygenase-1 and cyclooxygenase-2 , which then inhibits the production of prostaglandins in the stomach and intestines responsible for maintaining the mucous lining of the gastrointestinal tract. Indometacin, therefore, like other non-selective COX inhibitors can cause peptic ulcers.
It should always be taken with food. Nearly all patients benefit from an ulcer protective drug e. Other common gastrointestinal complaints, including dyspepsia , heartburn and mild diarrhea are less serious and rarely require discontinuation of indometacin.
Many NSAIDs, but particularly indometacin, cause lithium retention by reducing its excretion by the kidneys. Thus indometacin users have an elevated risk of lithium toxicity. For patients taking lithium e. All NSAIDs, including indometacin, also increase plasma renin activity and aldosterone levels, and increase sodium and potassium retention. Vasopressin activity is also enhanced. Together these may lead to: Edema swelling due to fluid retention Hyperkalemia high potassium levels  Hypernatremia high sodium levels Elevations of serum creatinine and more serious renal damage such as acute kidney failure , chronic nephritis and nephrotic syndrome , are also possible.
These conditions also often begin with edema and high potassium levels in the blood. Cases of life-threatening shock including angioedema , sweating, severe hypotension and tachycardia as well as acute bronchospasm , severe or lethal hepatitis and severe bone marrow damage have all been reported.
Skin reactions and photosensitivity are also possible side effects. The frequency and severity of side effects and the availability of better tolerated alternatives make indometacin today a drug of second choice.
Its use in acute gout attacks and in dysmenorrhea is well-established because in these indications the duration of treatment is limited to a few days only, therefore serious side effects are not likely to occur.
People should undergo regular physical examination to detect edema and signs of central nervous side effects. Blood pressure checks will reveal development of hypertension. Periodic serum electrolyte sodium, potassium, chloride measurements, complete blood cell counts and assessment of liver enzymes as well as of creatinine renal function should be performed.
No examinations are necessary if only the topical preparations spray or gel are applied. Rare cases have shown that use of this medication by pregnant women can have an effect on the fetal heart, possibly resulting in fetal death via premature closing of the Ductus arteriosus.
Its is a nonselective inhibitor of cyclooxygenase COX 1 and 2, the enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone -like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation. By inhibiting the synthesis of prostaglandins, indometacin can reduce pain, fever, and inflammation. Since the physiologic body pH is well above the pKa range of indometacin, most of the indometacin molecules will be dissociated into ionized form, leaving very little un-ionized form of indometacin to cross a cell membrane.
If the pH gradient across a cell membrane is high, most of the indometacin molecules will be trapped in one side of the membrane with higher pH. This phenomenon is called "ion trapping". The phenomenon of ion trapping is particularly prominent in the stomach as pH at the stomach mucosa layer is extremely acidic, while the parietal cells are more alkaline.
Therefore, indometacin are trapped inside the parietal cells in ionized form, damaging the stomach cells, causing stomach irritation. This stomach irritation can reduce if the stomach acid pH is reduced.
In addition to the class effect of COX inhibition, there is evidence that indometacin has the ability to reduce cerebral blood flow not only through modulation of nitric oxide pathways but also via intracranial precapillary vasoconstriction. Indometacin inhibits the superior salivatory nucleus, thus relieving this type of headache. Indometacin is an effective tocolytic agent ,  able to delay premature labor by reducing uterine contractions through inhibition of prostaglandin synthesis in the uterus and possibly through calcium channel blockade.
Indometacin readily crosses the placenta and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys. Other modes of action for indometacin are: it inhibits motility of polymorphonuclear leukocytes, similar to colchicine it uncouples oxidative phosphorylation in cartilaginous and hepatic mitochondria, like salicylates it has been found to specifically inhibit MRP multidrug resistance proteins in murine and human cells .
Shakamuro We linked 15, singleton pregnancies with premature rupture of membranes from a nationwide US obstetrics cohort to local temperature. PPROM before 26 weeks has a high morbidity and mortality, and the significant predictors of neonatal mortality and adverse outcomes were antibiotic prophylaxis, latency period, GA at birth and polihidrambios weight. Factor de von Willebrand. The similarities and differences underlying cervical remodeling in premature prelabor rupture of fetal membranes and spontaneous preterm labor with intact membranes are unexplored.