Acetylsalicylic Acid Intake Research Articles

Pharmacokinetic interaction in beagle dogs of antiplatelet drugs: acetylsalicylic acid, dipyridamole and calcium dobesilate

In clinical practice, the co-administration of antiplatelet drugs, such as acetylsalicylic acid (ASA) and dipyridamole (DP) and calcium dobesilate, is often recommended in order to obtain secondary prophylaxis against certain ischaemic diseases. Therefore the possible pharmacokinetic interactions between these three drugs were studied after a single-dose in beagle dogs. The plasma concentrations of ASA, DP and CaDb were measured by HPLC. It was found that the DP and CaDb kinetics were unaffected by concurrent intake of ASA, DP or CaDb. However, concurrent DP or CaDb improved the bioavailability of ASA, particularly the increased Cmax and (AUC).

Relationship between plasma PGE 2 level and changes in hemoglobin proportions during bleeding-induced anemia in adult rats

Reversion of hemoglobin proportions toward newborn values is a characteristic change found in blood of acutely bled adult rats. In this study, adult Sprague-Dawley rats were bled over a period of time until they became anemic by hematologic parameters. We measured plasma prostaglandin E 2 levels of anemic and control rats using double-antibody technique. A significant increase was recorded in bled plasma, and the value returned to unbled level when anemia was corrected. Acetylsalicylic acid intake during bleeding-induced anemia abolished the process of reverse switching of hemoglobin, as well as inhibited the increase in plasma PGE 2 levels. Changes in hemoglobin proportions due to phlebotomy were also blocked when acetylsalicylic acid was replaced by indomethacin. These observations are of significance in understanding, at least in part, the mechanism of reverse hemoglobin switching in adult rats undergoing erythropoietic stress.

The effect of acetylsalicylic acid on menstrual blood loss in women with IUDs

Fifty-three volunteer women using Copper T 220C IUDs, complaining of increased menstrual bleeding, received per os 1 g, three times a day, of acetylsalicylic acid, for 5 days, during their menstrual periods. Menstrual bleeding for each patient was measured at least once before treatment. Bleeding estimates were also performed from the second to the fifth treatment cycle. From the 53 women admitted to the study, only 13 subjects (24.7%) had pre-treatment menstrual bleeding of more than 80 ml; 40 subjects had less than 80 ml. The group with hypermenorrhea had slightly decreased (not significant) the amount of menstrual blood loss with acetylsalicylic acid intake. On the other hand, 67.1% of women with bleeding less than 80 ml observed a significant increase in menstrual blood loss.

Comparison of the effect of acetylsalicylic acid on platelet function in male and female patients with ischemic stroke

The aim of this study was to observe whether acetylsalicylic acid (ASA) had different effects in both sexes. Out of the ischemic stroke patients who were admitted to the National Taiwan University Hospital (NTUH), those who had not taken ASA or ASA-like drugs for more than 2 weeks were selected for this study. For the diagnosis of ischemic stroke, computed tomography (CT) of the brain was performed in all cases, and for differential diagnosis, other necessary procedures were employed in a few cases. The serum salicylate (SA) level was measured by Trinder's method, thromboxane B2 (TXB 2) and 6-keto-PGF1 by radioimmunoassay, threshold concentration of adenosine giphosphate (ADP) by Born's method, and circulating platelet aggregates (CPA) by Wu and Hoak's method. The present study showed that the means of serum SA levels after administration of the same dose of ASA were not significantly different between the two sexes. After ingestion of ASA, a single dose of 75 mg, 300 mg or 600 mg, or 300 mg 4 times a day, mean plasma TXB2 levels were significantly suppressed and mean threshold concentrations of ADP were significantly elevated in the two sexes. After administration of above-mentioned various doses of ASA, the abnormally high plasma TXB 2 levels and abnormally low threshold concentrations of ADP and CPA 2 ratios were significantly normalized in both male and female patients. Plasma 6-keto-PGF1 levels were not influenced by ingestion of ASA 75 mg, but significantly depressed by administration of ASA 300 mg in both sexes. There were no sex differences in the antiplatelet effect of ASA in this experiment.

Maternal ingestion of acetylsalicylic acid inhibits fetal and neonatal prostacyclin and thromboxane in humans

Small doses of maternal acetylsalicylic acid have proved to prevent preeclampsia. To study the mechanism of this action of acetylsallicylic acid, healthy women ingested 100 mg (n = 13) or 500 mg (n = 14) od acetylsalicylic acid during labor at term. The fetal prostacyclin synthesis, as assessed by the production of 6-ketoprostaglandin F1α (a metabolite of prostacyclin) by the umbilical artery, was reduced from 21.3 ± 1.6 ng/gm/min of dry weight in the controls (n = 25, mean ± SE) to 7.8 ± 1.1 ng/ml/min (p < 0.001) in infants of mothers receiving 500 mg of acetylsalicylic acid, but it was unchanged in infants with mothers receiving 100 mg of acetylsalicylic acid (19.5 ± 2.3 ng/gm/min). Maternal ingestion of 500 mg of acetylsalicylic acid also was accompanied by reduced (p < 0.10) urinary excretion of 6-ketoprostaglandin F1α in neonates during the first 3 days of life. The fetal platelet thromboxane A2 synthesis, as assessed by the release of thromboxane B2 (a metabolite of thromboxane A2) during spontaneous clotting of the umbilical blood (63.4 ± 4.2 pg/105 platelets, n = 22), was inhibited in infants born to mothers given 100 mg (14.0 ± 3.7 pg/105 platelets, p < 0.001) or 500 mg of acetylsalicylic acid (6.1 ± 3.5 pg/105 platelets, p < 0.001). The thromboxane B2 release by the umbilical artery (1.1 ± 0.1 ng/gm/min, n = 13) also was decreased in infants of mothers receiving 500 mg of acetylsalicylic acid (0.57 ± 0.1 ng/gm/min, n = 7, p < 0.01). Thus a small dose of maternal acetylsalicylic acid (100 mg) inhibits only the fetoplacental thromboxane A2 but leaves prostacyclin production unaffected.

Acetylsalicylic acid antagonizes the bleeding-induced changes in hemoglobin proportions in normal adult rats

Normal adult Sprague-Dawley rats were made anemic by repeated phlebotomy. Ion-exchange chromatography of anemic blood showed newborn like hemoglobin proportions, involving the same six hemoglobin components as is found when newborn and adult blood are compared. However, acetylsalicylic acid intake during anemia failed to demonstrate the changes in hemoglobin proportions, either totally or partially, depending upon the doses. Since acetylsalicylic acid inhibits prostaglandin synthesis, the data suggest that one or more prostaglandins may be involved in the process of reverse switching of hemoglobin in adult rat erythroid cells during erythropoietic stress.

Prostaglandin E2 binding sites in porcine oxyntic mucosa: effects of salicylates.

These studies were designed to examine the changes in the characteristics of prostaglandin E2 (PGE2) binding to porcine oxyntic mucosa in the response to oral ingestion of salicylates. Either acetylsalicylic acid (ASA) or salicylic acid (SA) was administered to conscious pigs (100 mg/kg in 30 mL of an equimolar concentration of NaHCO3) once a day for 1, 3, 10, or 20 days. In control experiments a similar volume of 0.3 M NaHCO3 was administered for similar durations. Mucosal ulceration and the characteristics of the binding of [3H]PGE2 to a 30 000 X g membrane preparation of oxyntic mucosa were examined. Generation of mucosal PGE2 was measured by radioimmunoassay. ASA treatment resulted in an increase in the number and severity of mucosal ulcers and a decrease in PGE2 levels within the first treatment day. By day 20 the degree of ulceration had decreased in spite of a persistent reduction of mucosal PGE2 generation. A variable degree of ulceration was observed in SA-treated animals. In control animals only a single class of binding sites for [3H]PGE2 was evident. After 3 days of ASA treatment a second class of binding sites with a high affinity dissociation constant appeared. There was a decrease in the high affinity binding of [3H]PGE2 after 20 days of ASA ingestion. Low affinity binding was not altered. ASA treatment resulted in a significant increase in specific binding capacities for both families of binding sites. SA treatment did not consistently alter PGE2 binding characteristics from control at any time period studied.(ABSTRACT TRUNCATED AT 250 WORDS)

What's New in Steroid and Nonsteroid Drug Effects on Gastroduodenal Mucosa?

A survey is given on the damaging effect of acetylsalicylic acid, other nonsteroidal antiinflammatory drugs and corticosteroids on the gastroduodenal mucosa. The results of blood loss studies and endoscopic investigations are reviewed. Also, the histologic aspects of such damage are discussed. Modern concepts of the pathophysiology of these lesions stress the cytoprotective role of endogenous prostaglandins. Epidemiologic data strongly support an association between frequent and heavy intake of acetylsalicylic acid and gastric ulcer as well as gastrointestinal bleeding, whereas the association with duodenal ulcers is far less clearly established. Conclusive evidence is currently unavailable proving the superiority of other nonsteroidal antiinflammatory drugs in this regard. The ulcerogenic potency of corticosteroids at least in the small or medium dose range probably has been overstated in the past. Intensive ulcer therapy making use of H2 receptor antagonists often allows healing of small ulcers with a diameter up to 1 cm despite continued treatment with low dose corticosteroids or nonsteroidal antiinflammatory drugs, whereas continuation of these drugs is associated with very poor healing in ulcers larger than this size. The danger of perforation has to be taken into consideration.

4393040 In-vitro diagnostic method for detection of acetylsalicylic acid ingestion : Alberto Lopapa, Theodore Hall assigned to Lopapa Institute Inc

In real-time systems, time is usually so critical that other parameters such as energy consumption are often not even considered. However, optimizing the worst energy consumption case can be a key factor in systems with severe power-supply limitations. In this paper we study several memory architectures using combined time and energy optimization models for real-time multitasking systems. Each task is modeled using Lock-MS, a method to optimize the WCET of a task, with an added set of constraints to model in the same way the WCEC (worst case energy consumption). Our tested hardware components focus on instruction fetching, including a lockable cache, a line buffer and a sequential prefetch buffer. We test a variety of instruction fetch alternatives optimizing time and energy consumption. Our results show that the accuracy of the estimation of the number of context switches in the worst case may affect very much the resulting WCEC (up to 8 times in our experiments) and that optimizing the WCEC may provide similar execution times than optimizing the WCET, with up to 5 times less energy consumption Additionally optimization functions combining WCET and WCEC with different weights show very interesting WCET-WCEC trade-offs. This confirms that methodologies testing such optimizations at design time could be very helpful to provide a precise system set-up.

Dose-related effect of acetylsalicylic acid on replication of varicella zoster virus in vitro.

Cultivation of human embryonic lung (HEL) cells in media containing acetylsalicylic acid (ASA) at 100 micrograms/ml and maintenance at this level after inoculation with either cell-free varicella zoster virus (VZV) or virus-infected cells resulted in a 2- to 4-fold increase in yields of cell-free virus released by sonication. The degree of enhancement was dependent upon multiplicity of infection and time of harvest. Enhanced viral yields were not consistently accompanied by an increase in the number of infected cells, nor was VZV plaque formation in HEL indicator cells significantly increased in the presence of ASA at 100 micrograms/ml. In the presence of ASA at 500-1000 micrograms/ml, VZV plaque formation was inhibited; this inhibition was partially reversible, depending on concentration and period of exposure to ASA. These findings may bear on the apparent association between ASA ingestion and the development of Reye syndrome after infection with varicella virus.

Drug interaction in middle molecule analysis, with special reference to acetylsalicylic acid.

Concerning the middle molecules in uremia and other diseases, the potential artifact that can impede an accurate quantitation of middle molecules and that is related to the absorption of a very commonly used drug, namely aspirin, is discussed. Peak 7c and peak b 4-2 are two different middle molecules separated by gel permeation chromatography followed by anion-exchange chromatography. Oral ingestion of acetylsalicylic acid modifies the chromatographic pattern of the middle molecule fraction in normal subjects and uremic patients. Peak 7c is increased in the urine of healthy subjects, whereas this is not the case for peak b 4-2: With the b 4-2 technique, ingestion of acetylsalicylic acid produces a higher peak b 5. This is consistent with the previous demonstration that peak 7c was eluted as peak b 5. Structural analogies between salicylate metabolites and orthohydroxyhippuric acid beta-glucuronate (i.e., the main component of peak 7c) could explain this drug-related artifact.

6 - Gastroduodenal Damage due to Drugs, Alcohol and Smoking

In man, convincing data have been obtained in short-term observations that some drugs can cause acute gastroduodenal damage including gastritis and erosions. Useful clinical and epidemiological studies on the relationship between these acute lesions and peptic ulceration, and between the chronic ingestion of these drugs and peptic ulceration or massive upper gastrointestinal haemorrhage are, however, rare. Even for the most widely used and studied greatest offender--acetylsalicylic acid (ASA)--an association with major bleeding or gastric ulceration could only be established for frequent and heavy ASA intake. The percentage of those ASA users who will experience such a serious event each year is about 0.01 to 0.05 per cent. By the use of special (e.g. enteric-coated) ASA formulations and other precautions, this low rate may be further reduced. Although for most of the other non-steroidal anti-inflammatory drugs (NSAIDs), anecdotal reports on putative drug-related major gastric bleeding or peptic ulceration exist, the ulcerogenicity of these drugs has not yet been conclusively proven in controlled studies. Some of the newer NSAIDs seem at normal dosage to be far less damaging than traditional ASA or indomethacin. Glucocorticoids might enhance ulcer risk to a minor extent when administered at high dosage for prolonged periods to susceptible individuals. Chronic moderate alcohol consumption by itself does not seem to increase the liability to peptic ulceration. With highly concentrated alcoholic beverages, gastric bleeding from acute lesions may, however, be occasionally precipitated under certain circumstances, such as when unbuffered ASA is taken concomitantly. Smoking of cigarettes is associated, and perhaps causally related, with an increased incidence of gastric and duodenal ulcerations, impaired ulcer healing, and more frequent ulcer recurrences. Duodenal ulcer patients in particular should be advised to stop smoking.

Plaque-forming cells in man. IV. Influence of acetylsalicylic acid in vivo and dexamethasone in vitro.

The influence of acetylsalicylic acid (ASA) and steroid (ST) on the number of plaque-forming cells (PFC) developed in pokeweed mitogen-activated cultures of peripheral blood lymphocytes (PBL) was investigated. Cultures of 10(6) PBL were established from blood samples of 16 healthy volunteers before and after intake of 2 g of ASA, and parallel cultures were supplemented with ST in vitro. The immunoglobulin secretion was monitored with a protein A assay. Our results show that pharmacological doses of ASA in vivo decrease the number of PFC by 41%, whereas the distribution of the subpopulations was unaltered. In cultures of PBL obtained before the intake of ASA and supplemented with 10, 50 or 100 micrograms/ml of dexamethasone the number of PFC was decreased by 50%, 41% and 44%, respectively. In cultures of PBL obtained after the intake of ASA and supplemented with 10, 50 or 100 micrograms of ST, the number of PFC was further decreased by 22%, 32% and 38%. The effects of ASA in vivo and ST in vitro were additive. The ratio of IgM, IgG and IgA PFC was unaffected by ASA and ST. It is suggested that the modulation of the PFC response induced by ASA and ST is mediated by the prostaglandin system.

Influence of sex, blood group, secretor character, smoking habits, acetylsalicylic acid, oral contraceptives, fasting and general health state on blood coagulation variables in randomly selected young adults.

Blood samples were drawn from 129 randomly selected young adults. Intake of acetylsalicylic acid (ASA), contraceptive drugs, smoking habits and health state were registered. Males had significantly higher systolic blood pressure, shorter bleeding time and lower VIII:C. Smoking was only correlated to some variables assessed in the female group. Users of oral contraceptives smoked more, had a shorter bleeding time and higher fibrinogen levels. Factor VIIIR;Ag was elevated only in female smokers with blood group non-O. Non-secretors had shorter bleeding times and a tendency towards higher VIIIR:Ag.

Recovery of cyclooxygenase activity after aspirin in populations of platelets separated on stractan density gradients

Human platelets obtained before and at intervals up to one week following the ingestion of 650 mg acetylsalicylic acid (ASA) were subjected to fractionation on discontinuous gradients of stractan. Platelets were recovered from the density gradients and incubated with arachidonate. Thromboxane synthesis was estimated by radioimmunoassay (RIA). There were no differences in cyclooxygenase activity among the platelet fractions prior to ASA ingestion. ASA inhibited synthesis of thromboxane B 2(TXB 2) by 98% in all subfractions. Twenty-four hours after ASA ingestion the total platelet population exhibited 10% of the control cyclooxygenase activity suggesting that new platelets emerging from the bone marrow within 24 hours of an ASA dose have functional cyclooxygenase enzymes. The pattern of return of TXB 2 synthesis differed markedly among the platelet fractions, indicating differences in the distribution of hew platelets among these fractions. New platelets with functional cyclooxygenase enzyme were twice as concentrated in the less dense fractions as in the most dense fraction. By 72 hours up to 75% of the platelets in the less dense fractions synthesized thromboxanes, while only 27% of platelets in the most dense fraction were active. Newly formed platelets may increase in density as they age or platelets of low density have a more rapid turnover than platelets of high density.

Effects of Acetylsalicylic-acid Ingestion on Maternal and Neonatal Hemostasis

In a case-control study, we evaluated the effects of maternal ingestion of acetylsalicylic acid (aspirin) within 10 days of delivery on maternal and neonatal hemostasis. Only one of 34 control maternal-neonatal pairs (3 per cent) had hemostatic abnormalities. In 10 pairs, when maternal aspirin ingestion occurred within five days of delivery, 6 of 10 mothers and 9 of the 10 infants had bleeding tendencies. Seven maternal-neonatal pairs in which aspirin was ingested 6 to 10 days before delivery were free of clinical bleeding. Among seven other mothers who ingested aspirin in the immediate post-partum period four of the seven (57 per cent) also had impaired hemostasis. Neonatal hemostatic abnormalities included numerous petechiae over the presenting part, hematuria, a cephalhematoma, subconjunctival hemorrhage, and bleeding from a circumcision. Maternal bleeding was confined to excessive intrapartum or post-partum blood loss. We conclude that aspirin should be avoided during pregnancy. If ingestion has occurred within five days of delivery, the neonate should be evaluated for the presence of bleeding.

Effects of Acetylsalicylic-Acid Ingestion on Maternal and Neonatal Hemostasis

In a case-control study, we evaluated the effects of maternal ingestion of acetylsalicylic acid (aspirin) within 10 days of delivery on maternal and neonatal hemostasis. Only one of 34 control maternal-neonatal pairs (3 per cent) had hemostatic abnormalities. In 10 pairs, when maternal aspirin ingestion occurred within five days of delivery, 6 of 10 mothers and 9 of the 10 infants had bleeding tendencies. Seven maternal-neonatal pairs in which aspirin was ingested 6 to 10 days before delivery were free of clinical bleeding. Among seven other mothers who ingested aspirin in the immediate post-partum period four of the seven (57 per cent) also had impaired hemostasis. Neonatal hemostatic abnormalities included numerous petechiae over the presenting part, hematuria, a cephalhematoma, subconjunctival hemorrhage, and bleeding from a circumcision. Maternal bleeding was confined to excessive intrapartum or post-partum blood loss. We conclude that aspirin should be avoided during pregnancy. If ingestion has occurred within five days of delivery, the neonate should be evaluated for the presence of bleeding.

Effects of Acetylsalicylic Acid Ingestion on Maternal and Neonatal Hemostasis

In a case-control study, we evaluated the effects of maternal ingestion of acetylsalicylic acid (aspirin) within 10 days of delivery on maternal and neonatal hemostasis. Only one of 34 control maternal-neonatal pairs (3 per cent) had hemostatic abnormalities. In 10 pairs, when maternal aspirin ingestion occurred within five days of delivery, 6 of 10 mothers and 9 of the 10 infants had bleeding tendencies. Seven maternal-neonatal pairs in which aspirin was ingested 6 to 10 days before delivery were free of clinical bleeding. Among seven other mothers who ingested aspirin in the immediate post-partum period four of the seven (57 per cent) also had impaired hemostasis. Neonatal hemostatic abnormalities included numerous petechiae over the presenting part, hematuria, a cephalhematoma, subconjunctival hemorrhage, and bleeding from a circumcision. Maternal bleeding was confined to excessive intrapartum or post-partum blood loss. We conclude that aspirin should be avoided during pregnancy. If ingestion has occurred within five days of delivery, the neonate should be evaluated for the presence of bleeding.

Systemic availability of acetylsalicylic acid in human subjects after oral ingestion of three different formulations.

Systemic availability of acetylsalicylic acid (ASA) in normal human subjects after oral ingestion of 1 g in three different formulations was determined by using high-pressure liquid chromatography for ASA assay. For an effervescent, a plain and a sustained release preparation systemic availabilities expressed in percent of the ingested dose were 16.9 +/- 3.2, 8.6 +/- 1.2 and 2.6 +/- 0.4%, respectively. All subjects had clearly measureable amounts of ASA in plasma after oral intake of a sustained release preparation with an average peak concentration of 15 mumol/l. Peak concentration after an effervescent and plain formulation was on the average 80 and 40 mumol/l, respectively. Half-life of ASA in plasma was 18.1 +/- 1.2 min. for the effervescent and 28.7 +/- 5.3 min. for the plain preparation, while the elimination phase was too ill defined for the sustained release formulation. Average plasma half-life of salicylic acid (SA) was similar after the three different administration forms with values between 3.0 and 3.7 hrs. Further, no difference in SA distribution volumes or amounts of SA absorbed was found. The present study demonstrates that oral ingestion of ASA in effervescent, plain and sustained release formulations gives rise to significant amounts of ASA in plasma. Concentrations found indicate that long-term antithrombotic therapy with ASA in a sustained release formulation may be possible.

The effect of acetylsalicylic acid on plasma glucose and the response of glucose regulatory hormones to intravenous glucose and arginine in insulin treated diabetics and normal subjects

The effects of oral acetylsalicylic acid (ASA) 3.2 g a day for 5 days on glucose and glucose regulatory hormones were examined in 4 normal subjects, and in 14 insulin requiring diabetic subjects, 9 of whom had significant residual Beta cell function as assessed by C-peptide secretion and 5 of whom did not. In all subjects plasma samples were assayed for glucose, C-peptide, glucagon, growth hormone, and cortisol during sequential intravenous glucose and arginine infusions while the subject was receiving ASA or placebo. The plasma samples from the normal subjects were assayed for insulin. ASA significantly increased early insulin release (p < 0.02) and decreased plasma glucose (p < 0.02) in response to intravenous glucose in the normal subjects. ASA had no effect on glucose or hormone responses to intravenous arginine. The C-peptide positive diabetics had a significantly lower basal plasma glucose while receiving ASA, and this difference persisted throughout the test (p < 0.02). C-peptide levels were similar to control during ASA ingestion. ASA had no significant effect on plasma glucose in the C-peptide negative diabetics. ASA significantly increased fasting plasma glucagon in the normal subjects (p < 0.05) and C-peptide negative diabetics (p < 0.05). There was a significant positive correlation between the changes in plasma glucose and plasma glucagon both basally and 10 min after the commencement of the glucose infusion for the C-peptide negative diabetics but not for the C-peptide positive diabetics or the normal subjects. ASA had no effect on plasma growth hormone or cortisol levels. The reduction of plasma glucose by ASA in man is dependent on continuing β cell function. In the absence of β cell function the stimulatory effect of ASA on glucagon production becomes the major determinant of ASA's effect on plasma glucose. The effects of ASA on pancreatic islet function appears to be the major determinant of its effect on glucose handling.