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[Acetylsalicylic acid treatment after peripheral vascular surgery].

Antiplatelet drugs (acetylsalicylic acid) have been widely used in arteriosclerotic patients during recent years. We have reviewed the literature to find out if this treatment also is indicated in patients operated with reconstructive vascular surgery for lower limb ischemia. It is concluded, that all patients should receive life-long treatment with acetylsalicylic acid 300-500 mg per day following peripheral vascular surgery. This will improve the patency rate of certain vascular procedures, and in all patients it reduces the incidence of cerebral stroke and the risk of myocardial infarction in the years following peripheral vascular surgery.

Anticoagulants↗

Effect of acetylsalicylic acid on the amphibian gastric mucosa. I. Electrophysiological and permeability changes.

The effects of acetylsalicylic acid on the in vitro bullfrog gastric mucosa were defined. After mucosal exposure of 10 or 20 mM acetylsalicylic acid, a characteristic series of changes evolved. The potential difference and resistance rose initially. After 15 to 30 min the potential difference declined to zero. Transmucosal resistance remained elevated considerably longer but began to decline toward zero after 30 to 60 min of exposure. Mucosal permeability to mannitol increased as transmucosal resistance declined, but was not markedly elevated until the 2nd hr of exposure to acetylsalicylic acid. The initial rise of potential difference was associated with inhibition of H+ secretion whereas the later decline of potential difference was due to inhibition of Cl- transport. The abolition of short circuit current could not be attributed to mucosal to serosal flux of acetylsalicylate.

Animals↗

[Utilization of the pharmacokinetic parameters of acetylsalicylic acid for optimizing its use with people of different ages].

Nomograms for application of acetylsalicylic acid in persons of different age are presented. The nomograms are based on pharmacokinetic parameters of acetylsalicylic acid with regard to the age. Proceeding from the known constants of absorption and elimination, the nomograms are made use of to screen the loading and maintenance doses, to determine the time of administering the first maintenance dose and the maximal amount of the drug in the body, which was built up as a result of the use of the accepted treatment schedule. While using the nomograms one should be guided by the known therapeutic dose and the dosage intervals or by the therapeutic or maximal allowable dose. The nomograms are unsophisticated, fairly convenient, and help determine the optimal regimen of the use of acetylsalicylic acid in persons of different age.

Adult↗

Trilinear PARAFAC decomposition of synchronous fluorescence spectra of mixtures of the major metabolites of acetylsalicylic acid.

Mixtures of the three major metabolites of acetylsalicylic acid (salicylic, gentisic and salicyluric acid) were analyzed by synchronous molecular fluorescence spectroscopy. Three-way data matrices were generated by acquisition of spectra as a function of the pH (between 2 and 11) and of different relative concentrations of the three components. The PARAFAC trilinear model, without restrictions and using one factor per metabolite, was used in the data analysis. A full decomposition of the data matrices into the spectra, concentration and pH profiles was obtained. This result shows that molecular fluorescence spectroscopy can be used for the development of robust analytical methods for the simultaneous determination of the three major metabolites of acetylsalicylic acid in complex background samples.

Air Pollutants, Occupational↗

Is ethanol-induced damage of the gastric mucosa a hyperosmotic effect? Comparative studies on the effects of ethanol, some other hyperosmotic solutions and acetylsalicylic acid on rat gastric mucosa.

The involvement of hyperosmolarity in ethanol-induced gastric mucosal damage was studied by comparing the effects of ethanol on the rat gastric mucosa and those caused by hyperosmotic glucose and choline chloride solutions, and by an almost isosmotic solution of acetylsalicylic acid. Upon intragastric instillation, all test solutions, namely 3M and 5M ethanol (3330 and 5590 mosmol/kg resp.), 3M glucose (3890 mosmol/kg), 1.5 M choline chloride (2840 mosmol/kg) and 20 mM acetylsalicylic acid, also containing 100 mM HCl and 50 mM NaCl, produced macroscopic and microscopic lesions of the gastric mucosa. The haemorrhages induced by ethanol and acetylsalicylic acid solutions were more evenly distributed, whereas most lesions produced by the glucose and choline chloride solutions were located at the rumeno-fundic junction. There were no qualitative differences between the microscopic lesions caused by the various instillates, however. All the test solutions broke the gastric mucosal barrier and increased histamine release and pepsinogen output, but in the rats treated with acetylsalicylic acid these effects were less pronounced. Ethanol, glucose and choline chloride solutions increased gastric mucosal flow and fluid output from the stomach, whereas acetylsalicylic acid had no effect on these. The similarity between the ethanol-induced changes and those caused by hyperosmotic solutions of glucose and choline chloride leads to the suggestion that ethanol may cause damage in the gastric mucosa at least in part, via hyperosmolarity.

Animals↗

Abuse of codeine separated from over-the-counter drugs containing acetylsalicylic acid and codeine.

In Denmark a new trend concerning the abuse of codeine has been observed. Danish drug abusers have discovered that codeine is easily separated from certain drugs containing acetylsalicylic acid and codeine. When separated the codeine can be used either orally or intravenously. Three different drugs combining acetylsalicylic acid and codeine are available in Denmark, but codeine is only easily separable from one of these. Applying the same procedure to the two other drugs produces unpredictable or unfavourable ratios of codeine to acetylsalicylic acid. In several countries, however, similar drugs combining acetylsalicylic acid and codeine are available. It is not possible from a list of constituents to predict how easily codeine can be separated from a particular drug. Therefore it is strongly recommended that relevant drugs are tested at local forensic laboratories. In case codeine is found to be very easily separated from a product appropriate action should be taken.

Aspirin↗

A pharmacokinetic approach to the establishment of biopharmaceutic characteristics of different acetylsalicylic acid formulations in man.

Eleven acetylsalicylic acid (ASA) formulations were administered to 26 healthy volunteers in a cross-over design. The properties of the preparations differed from conventional, effervescent, buffered to buccal. The objectives of this study were: Consideration of the general aspects of a biopharmaceutical study: which parameter for which biopharmaceutic characteristic? Measurement of the kinetic parameters of ASA: first-pass effect, mean residence time, mean appearance time, total body clearance, apparent volume of distribution, half-lives, etc. Comparison of the formulations. Most of the formulations yield mean residence times for ASA of 0.3-1.0 h, which do not differ significantly (p greater than 0.05). For most of the products the first-pass effect is about 40 per cent; the average values of the apparent volume of distribution and whole body clearance, corrected for the first-pass effect, are about 201 and 650 ml min-1, respectively. Peak levels are reached slowly for the buccal formulations, and rapidly for the buffered products. It is difficult, especially for ASA, to characterize the gastro-intestinal absorption with pharmacokinetic model parameters, because the first-pass effect is large and often elimination of ASA is faster than absorption. The model-independent approach has the special advantages of calculating reliable pharmacokinetic parameters, and creating theoretical possibilities to characterize the absorption patterns of the different formulations in a quantitative way. No significant differences in the values of the parameters are found between most of the formulations. The ASA first-pass effect is reasonably constant and buccal application has no advantage. Enteric coating of the outer layer of ASA formulations causes inconsistent absorption and may be categorized under 'artificial mistakes'.

Adolescent↗

Inhibition of platelet function by low-dose plain and micro-encapsulated acetylsalicylic acid.

The effect of two acetylsalicylic acid (ASA) formulations, plain (Magnyl) and micro-encapsulated (Globentyl), on platelet aggregation, thromboxane formation, and bleeding time was studied in 12 healthy volunteers in a randomized double-blind cross-over study. All subjects were treated with Magnyl and Globentyl (75 mg daily) in periods of 2 weeks, separated by a wash-out period of 2 weeks. Both drugs significantly depressed platelet aggregation and thromboxane formation and prolonged bleeding time without difference in mode of action of the drugs. It is concluded that significant inhibition of platelet activity may be achieved by low-dose ASA treatment with micro-encapsulated as well as with plain formulations.

Adult↗

Influence of cellulose powder structure on moisture-induced degradation of acetylsalicylic acid.

The stability of crystalline acetylsalicylic acid (ASA) powder in binary mixtures with cellulose powders was investigated to reveal information about the influence of the cellulose structural properties on the moisture-induced ASA degradation. Different cellulose powder samples were manufactured and characterized by X-ray diffraction and N2 BET gas adsorption. The degradation patterns in ASA/cellulose mixtures were monitored as a function of salicylic acid increase versus time under various relative humidity conditions at 50 degrees C. The crystallinity index of cellulose samples varied between approximately 49 and 95%. The results indicated that cellulose powder with the lowest crystallinity index exhibited lower degradation rates than the samples with the higher crystallinity index. It should be noted that higher ASA degradation rates were observed in the samples with comparably lower moisture contents. This effect was most pronounced in the 1:3 (w/w), ASA/cellulose mixtures, whereas in 3:1 (w/w), ASA/cellulose mixtures the effect was less obvious. The findings emphasise the importance of cellulose structural organisation when governing the moisture's partition between cellulose and ASA during the hydrolytic degradation.

Aspirin↗

Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.

Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was demonstrated in a series of clinical trials. The recommended ASA doses decreased gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2 production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml), 30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2 14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because of noncompliance verified by the determination of salicyluric acid urinary excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT platelet release did not decrease; (7) Potential changes of 5HT metabolic elimination were excluded by the simultaneous determination of 5-hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2 production without influence on 5HT release.

Aspirin↗

[Clinical pharmacology of acetylsalicylic acid].

The pharmacological actions of acetylsalicylic acid (ASA) are determined by two compounds: ASA and salicylic acid. Salicylic acid is formed from its precursor ASA within 15-20 min after oral application and is responsible for the antiinflammatory, antipyretic, and analgetic activities of ASA. However, the platelet inhibitory, i.e., the antithrombotic action of ASA is only due to this compound itself and is caused by irreversible inhibition of the platelet cyclooxygenase, i.e., inhibition of thromboxane A2 formation. The bioavailability of plain ASA after oral administration amounts to 40-50% at therapeutic doses. This is due to rapid deacetylation prior to reaching the systemic circulation. This deacetylation accounts for a significant part of inhibition of platelet cyclooxygenase within the portal circulation which is further enhanced by using sustained-release preparations. Doses of 40-50 mg ASA per day are sufficient to maintain complete blockade of platelet cyclooxygenase and this agrees well with the established efficacy of 75 mg ASA/day in controlled clinical trials on secondary prevention of myocardial infarction.

Administration, Oral↗

[Aspirin--the prodigious panacea? Molecular mechanisms of the action of acetylsalicylic acid in the organism].

Aspirin (acetylsalicylic acid) is a commonly used non-steroidal anti-inflammatory drug capable of acetylating proteins in the course of a simple, non-enzymatic chemical reaction. Its main physiological effect is inhibiting prostanoid synthesis. Cyclooxygenases, COX-1 and COX-2, are crucial in the metabolic pathway leading to the generation of prostanoids. Both enzymes are major cellular targets for aspirin. The physiological spectrum of the biological activity of the prostanoids is very broad, and underlies the high clinical effectiveness of aspirin as an anti-inflammatory, antipyretic, and analgesic drug. Apart from the inhibition of prostanoid synthesis aspirin shows a variety of pharmacological activities, including reduction of ATP storage pools, increased extracellular adenosine, lowered inducible nitric oxide synthase activity, modulation of mitogen-activated protein kinases, and the expression of a plethora of genes induced under conditions of cell stress via the regulation of transcription factor NFkappaB activity. Such multipotent action explains its wide use in clinical practice. Regardless of the accumulated evidence on the molecular mechanisms of aspirin's action, the rationale of the appropriate dosing and monitoring of aspirin therapy and prophylaxis remains obscure. Hence, an evaluation and reasonable weighing of the cost/benefit ratio of aspirin therapy in various diseases seems appropriate.

Analgesics↗

A double-blind, placebo-controlled study of acetylsalicylic acid (ASA) in trained runners.

Acetylsalicylic acid (ASA) is a short-acting oral inhibitor of the cyclooxygenase enzyme. Ingestion of ASA is associated with a decrease in prostaglandins, including those of the E2 series, as well as prostacyclin, and thromboxane. Consumption of therapeutic doses is associated with decreased pain and inflammation and is therefore used in a variety of inflammatory conditions. Platelet aggregation is also inhibited. Because of these observations, and the fact that platelet aggregation has been noted to be altered during exercise, the effects of ASA on exercise tolerance was of interest. We studied 17 healthy male volunteers who regularly ran as a source of exercise. During the study they ingested either 650 mg of ASA or placebo 30 min before running 2 miles (3.2 km). Outcome of the double-blind crossover study was measured by the time required to run a 2-mile distance. No differences between ASA or placebo were noted in the subjects. These data suggest that 650 mg of ASA as a premedication has little effect on exercise performance in normal endurance runners. However, whether ASA may affect pain after exercise or whether other dosage intervals would be more beneficial needs further study.

Adult↗

Stimulatory effects of vascular prostaglandins on the antiaggregatory activities of pentoxifylline acetylsalicylic acid combinations in vitro.

Pentoxifylline, Acetylsalicylic acid (ASA) and particularly both drugs in combination are known as active platelet inhibitors in pharmacological models in vivo. However, rather high amounts of these drugs are necessary to demonstrate inhibitory effects on the aggregation of human platelets in vitro, where no vessel walls are present. Surprisingly, these weak effects could be enhanced by the addition of external prostaglandins (prostacyclin (PGI2) and prostaglandin E1 (PGE1] into the in vitro system. Ternary combinations consisting of pentoxifylline, ASA and PGI2 exhibited the most impressive synergistic effects. Thus our study highlights the contribution of prostaglandins, especially of the natural vascular platelet inhibitor PGI2, for the display of the antiaggregatory potency of such drug combinations.

Alprostadil↗

Methodology of kinetic interaction studies in clinical pharmacology: an experimental contribution on diftalone and acetylsalicylic acid.

The possible interaction of acetylsalicylic acid (ASA) and diftalone (DIF), a new anti-inflammatory drug, was studied in 6 volunteers. All subjects received each of the following three treatments: ASA 1 g, DIF 0.5 g, ASA 1 g plus DIF 0.5 g at 4-day intervals (stage 1 of the study). In stage II of the same study, each subject received ASA 1 g plus DIF 0.5 g in three different occasions 1 week apart; after a 7-day pre-treatment with either DIF 0.25 g b.i.d., or ASA 0.5 g b.i.d., or DIF 0.25 g b.i.d. plus ASA 0.5 g b.i.d. A total of four different comparisons were made. After pre-treatment with DIF, but not after pre-treatment with DIF plus ASA, the peak level of salicylate was significantly reduced by about 15%. No other evidence of interaction was found.

Adult↗

Immunogenicity of aryl esters of salicylic or acetylsalicylic acid in guinea pigs.

A variety of derivatives of acetylsalicylic and salicylic acid have been investigated for their immunogenic properties in guinea pigs including salicylsalicylic acid (SSA), acetylsalicylsalicylic acid (ASSA), disalicylide (DI), trisalicylide (TRI), acetylsalicylic acid paracetamol ester (ASPE) and acetylsalicylic acid guajacol ester (ASGE). Contact sensitivity could be elicited by the sensitizing agent, however, with acetylsalicylic acid anhydride (ASAN) a more pronounced contact reaction could consistently be observed. Systemic anaphylactic reactions elicited by intravenous injection of N-salicyloyl bovine serum albumin could only be induced by ASAN, DI, TRI and ASSA, whereas SSA, ASPE and ASGE did not induce an anaphylactic state at a comparable dose level. From these results it is anticipated that all aryl esters of acetylsalicylic or salicylic acid are immunogenic when applied intradermally, leading to a N-salicyloyl specific immune response.

Acetylation↗

Proton-pump inhibitor therapy for acetylsalicylic acid associated upper gastrointestinal symptoms: a randomized placebo-controlled trial.

OBJECTIVE: Patients using acetylsalicylic acid (aspirin) have an increased risk of upper gastrointestinal discomfort. The aim of this study was to assess whether gastric acid suppression improves upper gastrointestinal symptoms in patients using low-dose aspirin for cardiovascular disease. METHODS: In a double-blind, placebo-controlled randomised trial, 150 patients using low-dose (80 mg) acetylsalicylic acid with upper gastrointestinal symptoms who had been admitted at the Coronary Care Unit of the University Medical Center Nijmegen were assigned to treatment with rabeprazole (20 mg once daily) or placebo for 4 weeks. Treatment success, defined as complete upper gastrointestinal symptom relief, could be evaluated in 143 patients. RESULTS: At 4 weeks after randomization, 34 of the 73 patients assigned to rabeprazole therapy (47%) as compared with 30 of the 70 patients given placebo (43%) reported complete upper gastrointestinal symptom relief (P = 0.54). Rabeprazole therapy did lead to a 52% improvement of heartburn symptoms [25% vs. 16%; odds ratio (OR) 0.48, 95% confidence interval (CI): 0.24-0.97]. Epigastric pain, regurgitation, bloating and nausea symptoms did not statistically change after treatment. Patients with a history of dyspepsia more often reported treatment success in comparison to those without (75% vs. 40%; OR 0.25, 95% CI: 0.09-0.70). CONCLUSIONS: Proton-pump inhibitor therapy significantly reduced heartburn, but not other acetylsalicylic acid associated symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease.

Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we are dealing not merely with an in vitro phenomenon but with a significant in vivo effect. The study provides the rationale for clinical evaluations of low-dose acetylsalicylic acid in stroke prophylaxis.

Aged↗