Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basic proteinase inhibitor from bovine organs, aprotinin, was first identified in 1930 and its effect on enzyme and other biological systems has since been extensively studied. Aprotinin can only be administered intravenously and has a half-life of about 2 hours. Its administration at the start of cardiopulmonary bypass surgery appears to reduce blood loss and to protect against global myocardial ischaemia. Similarly, a smaller infarct size seems to result from early administration of aprotinin within the first hour after myocardial infarction, though further studies are needed to confirm this effect. A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used. Aprotinin is also effective as adjuvant treatment in traumatic haemorrhagic shock. The recommended loading dose is 15,000 to 20,000 KIU/kg bodyweight administered as a short intravenous infusion, followed by 50,000 KIU/hour by continuous infusion. Side effects of aprotinin are very rare. Epsilon-Aminocaproic acid (EACA), p-aminomethylbenzoic acid (PAMBA) and tranexamic acid are synthetic antifibrinolytic amino acids. Saturation of the lysine binding sites of plasminogen with these inhibitors displaces plasminogen from the fibrin surface. On a molar basis tranexamic acid is at least 7 times more potent that epsilon-aminocaproic acid and twice as potent as p-aminomethylbenzoic acid. All 3 compounds are readily absorbed from the gastrointestinal tract and excreted in active form in the urine. The plasma half-life of tranexamic acid is about 80 minutes. The main indications for tranexamic acid are the prevention of excessive bleeding after tonsillectomy, prostatic surgery, and cervical conisation, and primary and IUD-induced menorrhagia. It is possible that gastric and intestinal bleeding can also be reduced as well as recurrent epistaxis. Tranexamic acid could also be useful after ocular trauma. The value of fibrinolysis inhibitors in the prevention of bleeding after tooth extraction in patients with haemophilia is well documented, as is the treatment of hereditary angioneurotic oedema. The usual dose of tranexamic acid is 0.5 to 1g (10 to 15 mg/kg bodyweight) given intravenously 2 to 3 times daily, or 1 to 1.5 g orally 3 to 4 times daily. This dose needs to be reduced in patients with renal insufficiency. The main side effects of tranexamic acid are nausea or diarrhoea.
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PMID:Clinical application of inhibitors of fibrinolysis. 258 Jun 84

Safety, tolerance, and pharmacology of 9-beta-methylcarbacyclin calcium (ciprostene calcium) was investigated in healthy male volunteers. This stable prostacyclin analogue was infused intravenously into groups of 12, 11, and three volunteers for three, six, and eight hours, respectively, in doses up to 480 ng/kg/min. Based on the tolerance data obtained, a single-blind, placebo-controlled study was conducted. Seven subjects were infused for 8 hr/d for three days with ciprostene at a maximum dose of 160 ng/kg/min and seven subjects received placebo. One subject from each group did not complete the infusion schedule, and they were not included in the final analysis. During infusion of ciprostene, consistent changes in blood pressure and heart rate did not occur. Most frequent adverse drug reactions consisted of headache, restlessness, nausea, perspiration, flushing, and jaw pain. As compared with placebo, ADP-induced platelet aggregation was inhibited during the infusion period (P = .048). Significant (P = .04) elevations of platelet cyclic AMP were observed in subjects during infusion of ciprostene. Pre- versus postinfusion routine laboratory evaluations, fibrinogen concentration, antiplasmin activity, and plasminogen and template bleeding times remained unchanged. Placebo- and drug-treated subjects had a daily postinfusion shortening of euglobulin clot lysis time (ECLT). The preinfusion minus postinfusion ECLT for ciprostene subjects on days 2 and 3 (133 and 118 min, respectively) compared with placebo (239 and 217 min) suggest a trend to increased fibrinolytic activity. Based on the outcome of this trial, it is estimated that ciprostene is about 15 times less potent than prostacyclin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tolerance and pharmacology of ciprostene, a stable epoprostenol (prostacyclin) analogue in humans. 300 77

The clinical experience with a combined oral contraceptive (COC) containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol is reviewed. Fourteen clinical trials have been reported involving over 44,000 women for more than 190,000 cycles. None of the 17 pregnancies which occurred (overall Pearl Index 0.12) were due to method failure. The incidences of breakthrough bleeding and spotting after 6 treatment cycles varied from 0.1-6.0% and 2.8-11% of subjects, respectively, and at this time they were not significantly different from pretreatment in most trials. About 90% of subjects maintained regular cycles. The incidence of subjective side effects (approximately 5% for headache, 4% for breast tenderness, 2% for nausea) was low. No significant changes occurred in body weight or blood pressure. In all trials, the COC was well accepted and the rates of discontinuation were similar to those in other COC trials. Pharmacodynamic effects have been widely investigated. There were no significant changes in glucose metabolism or in haematological factors except for possibly minor increases in factors VII and X, fibrinogen and plasminogen. Over thirty studies of the effect of the COC on lipid metabolism have been published; significant increases occur in serum triglycerides, HDL-C and apoprotein A1. SHBG concentrations increase 2-3 fold with a consequent decrease in the levels of free testosterone. This effect can be particularly important therapeutically in women with hyperandrogenic skin disorders and 14 trials in women with these disorders have demonstrated significant clinical improvement with the COC. The findings from the various trials show the COC to be effective and acceptable with no adverse metabolic effects.
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PMID:Twelve years of clinical experience with an oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel. 775 Feb 81

Tranexamic acid (Transamin), Cyklokapron, Exacyl, Cyklo-f) is a synthetic lysine derivative that exerts its antifibrinolytic effect by reversibly blocking lysine binding sites on plasminogen and thus preventing fibrin degradation. In a number of small clinical studies in women with idiopathic menorrhagia, tranexamic acid 2-4.5 g/day for 4-7 days reduced menstrual blood loss by 34-59% over 2-3 cycles, significantly more so than placebo, mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone at clinically relevant dosages. Intrauterine administration of levonorgestrel 20 microg/day, however, produced the greatest reduction (96% after 12 months) in blood loss; 44% of patients treated with levonorgestrel developed amenorrhoea. Tranexamic acid 1.5 g three times daily for 5 days also significantly reduced menstrual blood loss in women with intrauterine contraceptive device-associated menorrhagia compared with diclofenac sodium (150 mg in three divided doses on day 1 followed by 25 mg three times daily on days 2-5) or placebo. Tranexamic acid, mefenamic acid, etamsylate, flurbiprofen or diclofenac sodium had no effect on the duration of menses in the studies that reported such data. In a large noncomparative, nonblind, quality-of-life study, 81% of women were satisfied with tranexamic acid 3-6 g/day for 3-4 days/cycle for three cycles, and 94% judged their menstrual blood loss to be 'decreased' or 'strongly decreased' compared with untreated menstruations. The most commonly reported drug-related adverse events are gastrointestinal in nature. The total incidence of nausea, vomiting, diarrhoea and dyspepsia in a double-blind study was 12% in patients who received tranexamic acid 1g four times daily for 4 days for two cycles (not significantly different to the incidence in placebo recipients). In conclusion, the oral antifibrinolytic drug tranexamic acid is an effective and well tolerated treatment for idiopathic menorrhagia. In clinical trials, tranexamic acid was more effective at reducing menstrual blood loss than mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone. Although it was not as effective as intrauterine administration of levonorgestrel, the high incidence of amenorrhoea and adverse events such as intermenstrual bleeding resulting from such treatment may be unacceptable to some patients. Comparative studies of tranexamic acid with epsilon - aminocaproic acid, danazol and combined oral contraceptives, as well as long-term tolerability studies, would help to further define the place of the drug in the treatment of menorrhagia. Nevertheless, tranexamic acid may be considered as a first-line treatment for the initial management of idiopathic menorrhagia, especially for patients in whom hormonal treatment is either not recommended or not wanted.
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PMID:Tranexamic acid: a review of its use in the management of menorrhagia. 1282 66