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PubMed2005

[Primary prevention of cardiovascular disease with acetylsalicylic acid: in high-risk patients].

In the recently published placebo-controlled 'Women's health study', use of acetylsalicylic acid 100 mg daily in healthy women older than 45 years protected against having a stroke. In men, higher doses of acetylsalicylic acid protects against myocardial infarction. However, risk reduction using acetylsalicylic acid is only clinically relevant if the absolute risk of cardiovascular disease is high. Countering vascular-risk factors reduces the chance of cardiovascular complications much more than the use of acetylsalicylic acid and therefore should be pursued without any reservation.

Age Factors↗
PubMed1984

Piroxicam, acetylsalicylic acid and placebo for postoperative pain.

A double-blind comparison of the pain-relieving effect of piroxicam 5 and 10 mg, acetylsalicylic acid 648 mg and placebo was performed in 120 patients with moderate to severe pain on the morning after orthopedic surgery. The changes in pain intensity and pain relief during the 8 h following medication were recorded by a trained nurse observer. 67% of the placebo-treated patients needed rescue drugs compared to 41% of the acetylsalicylic acid, 43% of the piroxicam 5 mg, and 45% of the piroxicam 10 mg treated patients. One to three hours after ingestion of the test drug, the piroxicam and the acetylsalicylic acid groups had significantly improved verbal rating pain intensity scores compared to placebo. In the overall assessment of pain relief at the end of the observation period, the patients' own assessment was significantly superior for acetylsalicylic acid and piroxicam 10 mg compared with placebo. In the observer's assessment of overall pain relief, placebo was significantly inferior to the three other groups. Thus piroxicam 5 mg and 10 mg give relief of pain after orthopedic surgery similar to that given by acetylsalicylic acid 648 mg. The pain-relieving effect of these drugs can be distinguished from placebo, but not from each other. They are not potent enough when pain is moderate to severe after orthopedic surgery.

Adolescent↗
PubMedDate not supplied

[Effect of various combinations of DL-alpha-tocopherol and acetylsalicylic acid on adjuvant arthritis in the rat].

The influence of per os application of different combinations of DL-alpha-tocopherol (TOC) and acetylsalicylic acid (ASS) on adjuvant-induced arthritis was tested in male Wistar rats (body weight 227 +/- 18 g; 8 groups, n = 8). One group (control) was without adjuvans arthritis and received no treatment, another group was also not treated in spite of adjuvans arthritis. Further, six groups of adjuvans arthritis were treated with the following combinations: ASS/TOC (mg/kg BW/d each) 250/-, 250/250, 167/250, 83/250, 167/167 and 167/83. During the course of the experiment (21 d), body weights, food intake, and the swelling of injected and noninjected paws, and (at the end of the test period) relative weight of spleen and the albumin-globulin-ratio in plasma were recorded. With the ASS/TOC combination of 250 mg/kg BW each, the highest antiinflammatory effect could be reached, as compared with all treated groups. The reduction of acetylsalicylic acid does by one-third to 167 mg/kg BW in combination with 250 mg DL-alpha-tocopherol/kg BW seem to have the same antiphlogistic effect as acetylsalicylic acid alone at 250 mg/kg BW. This positive effect could be confirmed by the partially normalized relative spleen weight and albumin-globulin-ratio. The results allow the conclusion: --main antiphologistic effect of the combination is due to acetylsalicylic acid; --when combined with 250 mg DL-alpha-tocopherol/kg BW acetylsalicylic acid dosage can be reduced by one-third to 167 mg/kg BW and still have the same effect as ASS alone (250 mg/kg BW); --further reductions of ASS and/or DL-alpha-tocopherol dosage minimize the antiinflammatory effect.

Animals↗
PubMed1998

Acetylsalicylic acid potentiates the antinociceptive effect of morphine in the rat: involvement of the central serotonergic system.

Acetylsalicylic acid and morphine are the most widely distributed and most frequently used drugs in the relief of pain, but their analgesic activity has adverse side-effects. Mixtures containing these two drugs are frequently used to relieve mild to moderate pain despite the paucity of relevant experimental evidence so far published. We set out to study the possible antinociceptive effect of a combination of subactive doses of the two drugs in rats. A combination of low doses of acetylsalicylic acid (50 mg/kg i.p.) and morphine (3 mg/kg s.c.) was administered and the pain threshold was evaluated in the hot-plate and formalin tests, and 5-HT2 receptor binding capacity, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in the cortex and pontine areas of the brain. The combination of acetylsalicylic acid and morphine had an analgesic effect in both tests that was associated with an increase in 5-HT levels and a decrease in 5-HT2 receptors in the cortex. These effects were either completely abolished or partially prevented by i.p. pretreatment with naloxone (1 mg/kg i.p.). Our results demonstrate that subactive doses of acetylsalicylic acid and morphine can exert analgesic and biochemical effects when given in combination in the rat and suggest an involvement of serotonergic and opiatergic systems.

Analgesics↗
PubMed1979

Physico-chemical analysis of systems with a main component acetylsalicylic acid in ethanol-water mixtures. Part 3: Systems containing calcium acetylsalicylate.

The systems C9H8O4-(C9H7O4)2Ca-25% ethanol-water mixture (I), C9H8O4-(C9H7O4)2Ca-50% ethanol-water mixture (II), C9H8O4-(C9H7O4)2Ca-95% ethanol-water mixture (III) have been investigated at 15 degrees C by physico-chemical analytical methods. It was established that under the conditions of the no experiments no double or triple compounds of acetylsalicylic acid and calcium acetylsalicylate have been formed. The fields of the crystallization of the pure components are outlined. In systems I and II there exist crystallization fields of (C9H7O4)2Ca - 2H2O and in system III field of (C9H7O4)2Ca. The anhydrous salt and the crystalline hydrate were isolated and were investigated by chemical analysis and X-ray diffraction analysis.

Aspirin↗
PubMed1986

Oral acetylsalicylic acid improves patency rates in small-vessel anastomoses.

Because platelet aggregation is the critical step in vascular thrombosis, this study investigated the possibility that acetylsalicylic acid given orally would improve patency of anastomoses in small arteries. Under clean conditions, in male Sprague-Dawley rats, the superficial femoral arteries were divided and reanastomosed using the sleeve technique with 10-0 nylon suture. Fifty-one rats received a full laboratory diet and acetylsalicylic acid in their drinking water (1.08 mg/ml), before and after operation. A control group of 54 rats was matched for weight, water intake and duration of vessel occlusion. Vessel patency was assessed on postoperative day 7, at sacrifice, by dye angiography. In the experimental group 7 (13.7%) anastomoses became occluded, compared with 20 (37.0%) in the control group (chi 2 = 5.99, df = 1, p less than 0.025). Serum thromboxane B2 levels in five rats given acetylsalicylic acid orally (33.1 +/- 6.1 ng/ml) were significantly (p less than 0.001) lower than in five control rats (86.6 +/- 49.1 ng/ml). The authors concluded that acetylsalicylic acid administered in the drinking water to Sprague-Dawley rats improved the patency rate of femoral artery anastomoses probably because of a reduction in platelet aggregation. Orally administered acetylsalicylic acid may be of clinical benefit to patients who undergo small-vessel anastomoses.

Administration, Oral↗
PubMed1990

The effects of acetylsalicylic acid on phosphoenolpyruvate carboxykinase activity and acinar heterotopy in livers from juvenile and adult rats.

Male and female juvenile as well as adult rats were treated with acetylsalicylic acid in order to examine the effect of the drug on over-all activity and activity distribution of phosphoenolpyruvate carboxykinase (PEPCK) in the liver acinus. Upon administration of acetylsalicylic acid PEPCK activity increased in juvenile males and adult females, but was reduced in juvenile females and adult males. The periportal-perivenous activity gradient along the sinusoidal length, which is flatter in untreated juvenile rats compared to the livers of adult rats, was distinctly steepened by acetylsalicylic acid treatment. Acetylsalicylic acid did not affect the gradient in adult rats.

Aging↗
PubMed1995

Pilot trial of the effects of low-dose acetylsalicylic acid on platelet thromboxane B2 production.

OBJECTIVE: It has been suggested that certain foods of plant origin contain milligram-quantities of acetylsalicylate which could exert an anti-thrombotic effect. Acetylsalicylic acid prevents cardiovascular diseases through inhibition of platelet endoperoxide thromboxane production and platelet aggregation. We investigated whether a daily intake of 3 mg acetylsalicylic acid causes a measurable decrease of platelet cyclo-oxygenase activity assessed by in vitro thromboxane B2 production. DESIGN: We carried out a randomised, double-blind, placebo-controlled cross-over study. SUBJECTS: Ten healthy volunteers (5 men, 5 women) aged 22 +/- 3 years (mean +/- s.d) participated in the study; there were no drop-outs. INTERVENTIONS: Participants took 3 mg/d of acetylsalicylic acid or a placebo for 2 weeks each. At the end of each treatment period venous blood was drawn, and platelet-rich plasma was stimulated with arachidonic acid. RESULTS: Treatment with acetylsalicylic acid caused a 39 +/- 8% decrease in maximal thromboxane B2 production (P = 0.000), which was independent of treatment order. CONCLUSIONS: Quantitative data on acetylsalicylate in foods and the possible antithrombotic action of a diet rich in acetylsalicylate deserve closer investigation.

Adult↗
PubMed1993

A clinical trial of a slow-release formulation of acetylsalicylic acid in patients at risk for preeclampsia.

The formation of thromboxane A2 (TXA2) in maternal and foetal cord serum was measured at birth in eight control patients and in 13 patients taking 100 mg of a slow-release formulation of acetylsalicylic acid. The serum concentrations of TXB2 (a stable end product of TXA2 hydrolysis) in both maternal and cord serum from patients who ingested the acetylsalicylic acid formulation were significantly lower (P < 0.01) than those in control subjects. Acetylsalicylic acid was not detected (< 30 ng ml-1) in maternal plasma from six mothers and in cord plasma from seven foetuses in the acetylsalicylic acid-treated group. The mean cord to maternal plasma concentration ratios for detectable acetylsalicylic acid and salicylate were 0.62 +/- 0.19 (s.d.) (n = 6) and 0.84 +/- 0.16 (n = 13), respectively. We conclude that low doses of acetylsalicylic acid given in a slow-release form to mothers during pregnancy cause depression of TXA2 formation in the foetal blood.

Adult↗
PubMed1976

Colorimetric analysis of immunogenic impurities in acetylsalicylic acid.

A rapid and convenient colorimetric method is described for the quantitative determination of the immunogenic impurities in acetylsalicylic acid, acetylsalicylsalicylic acid and acetylsalicylic anhydride. The method involves initial aminolysis of the compounds by ammonia to give salicylamide and subsequent coupling of this with 4-amino-phenazone in the presence of an oxidizing agent. In conjunction with a previously described method for analysis of the anhydride the method allows a specific determination of acetylsalicylsalicylic acid in concentrations down to 0-005%. Applying the methods to 15 different commercial acetylsalicylic acid samples and formulations, acetylsalicylic anhydride and acetylsalicylsalicylic acid were found to be present in amounts ranging from 0-001 to 0-024% and from 0-006 to 0-58% (w/w), respectively.

Anhydrides↗
PubMed1993

[Urticaria-angioedema type of sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs; diagnostic value of anamnesis and challenge tests with acetylsalicylic acid in detecting this sensitivity].

The aim of the paper was to estimate the value of challenge tests with acetylsalicylic acid in diagnosis of ASA-induced urticaria. The study was performed in 71 persons with suspected urticaria/angioedema type of sensitivity to ASA. The anamnesis confirmed sensitivity in 67 examined patients (94.4%) and showed that the sensitive patients usually suffered from extensive urticaria (37 persons, i.e. 55.5%) after ingestion of ASA. Eight persons (12%) reacted with loss of consciousness and 4 (6.0%) with oedema of the larynx. Oral challenge test with acetylsalicylic acid was performed in 53 examined persons, in 49 (92.4%) of which it was positive. Threshold doses of acetylsalicylic acid ranged from 40 to 300 mg. In 11 persons the test was repeated and in 8 performed three times. It was observed that both the threshold acetylsalicylic acid doses and the time of appearance of the sensitivity symptoms were changeable. All ASA-sensitive reacted to indomethacin in the similar way as to ASA. Paracetamol, on the other hand, was well tolerated by all 25 tested patients with urticaria/angioedema type of sensitivity to ASA.

Adolescent↗
PubMedDate not supplied

[Mechanisms of interaction of acetylsalicylic acid and indomethacin with endoperoxide prostaglandin synthetase].

A study was made of the character and kinetics of interaction of acetylsalicylic acid and indomethacin with endoperoxide prostaglandin synthetase (PGH-synthetase) of sheep vesicular glands and human platelets. Enzymatic activity of PGH-synthetase was determined polarographically with the aid of Clark's electrodes. Acetylsalicylic acid was found to inhibit PGH-synthetase of sheep vesicular glands and human platelets at concentrations of the order of 1 x 10(-6) and 1 x 10(-4) M, whereas indomethacin at concentrations of 1 x 10(-6) and 1 x 10(-7) M, respectively. Acetylsalicylic acid inhibited PGH-synthetase from sheep vesicular glands and that from human platelets at an equal rate. Indomethacin inhibited the enzyme from sheep vesicular glands to a higher degree. Indomethacin reversibly interacted with PGH-synthetase. Meanwhile acetylsalicylic acid inhibited this enzyme irreversibly.

Animals↗
PubMed1988

Post-tonsillectomy haemorrhage and analgesics. A comparative study of acetylsalicylic acid and paracetamol.

In a prospective randomized clinical study the incidence of post-tonsillectomy haemorrhage was studied in 832 patients receiving either acetylsalicylic acid or paracetamol as postoperative analgesic (423 and 409 patients, respectively). Of 27 patients experiencing 1 or more bleeding episodes postoperatively, 18 received acetylsalicylic acid and 9 paracetamol. No difference was found regarding the incidence of bleeding within the first 24 h but, later on, a significantly lower incidence of secondary bleeding occurred in the paracetamol group (0.5%) compared with the acetylsalicylic acid group (3.1%). We conclude that acetylsalicylic acid is not the optimum postoperative analgesic following tonsillectomy and that other alternatives must be sought.

Acetaminophen↗
PubMed1976

Inhibition of human and animal platelet adhesiveness to glass bead columns by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid.

The differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Adenosine↗
PubMed1996

Acetylsalicylic acid may protect the patient by increasing fibrin gel porosity. Is withdrawing of treatment harmful to the patient?

The effect of acetylsalicylic acid in preventing cardiovascular complications is ascribed to acetylation of the enzyme cyclo-oxygenase thereby inhibiting prostaglandin synthesis. Acetylsalicylic acid, however, also acetylates fibrinogen. In the present pilot study, we investigated the permeability, i.e. porosity, of the fibrin gel in male patients with stable angina pectoris treated with this drug before and at 1 and 2 weeks after withdrawal. Ten patients were treated with 75 mg and eight with 160 mg. The results were compared to those in seven untreated healthy controls. Bleeding times were longer during treatment and were reduced after withdrawal indicating patient compliance. Fibrin gels were more porous during treatment although there were large inter-individual variations in porosity. One week after withdrawal, the porosity was reduced by 30 41%, i.e. the network became tighter (75 mg group P = 0.001; 160 mg group P = 0.002). The tightness was more pronounced after withdrawal than in the untreated controls. In conclusion, the protective effect of acetylsalicylic acid may be ascribed to its effect not only on platelets but also on fibrinogen. The withdrawal of acetylsalicylic acid may clause a markedly reduced fibrin gel porosity that we assume is disadvantageous in patients with cardiovascular disease.

Adult↗
PubMed1982

Serum levels of free fatty acids in the first trimester of pregnancy: effect of acetylsalicylic acid.

The serum levels of free fatty acids were determined before and after an oral dose of 1000 mg acetylsalicylic acid (ASA) during the 7-11th weeks of pregnancy in 11 women admitted to hospital for legal abortion and in 8 women admitted for operative (hysterectomy) treatment because of fibroids. Thirteen healthy women of reproductive age served as controls. The levels of linoleic, alpha-linolenic, myristic, oleic, palmitic and palmitoleic acids were significantly lower in pregnant women than in the hysterectomy group. The level of arachidonic acid was higher in the pregnant and hysterectomy groups than in controls. Serum free fatty acids had a negative correlation with the duration of pregnancy. ASA treatment tended to increase the levels of many fatty acids in serum. Serum arachidonic acid levels after ASA treatment correlated significantly with the salicylate concentrations in myometrium and the levels of most other fatty acids with the salicylate concentration in endometrium.

Adult↗
PubMed1979

Gastrointestinal blood loss caused by controlled-release and conventional acetylsalicylic acid tablets.

Gastrointestinal blood loss has been studied following oral administration of the novel controlled-release acetylsalicylic acid tablet preparation Acetard and the instant-release acetylsalicylic acid tablet Magnecyl (Ph. Nord. 63). Acetard contains micro-encapsulated acetylsalicylic acid crystals having an in vitro release time of approximately 4 hours. The investigation was carried out as a two-part, randomized cross-over trial, and with a test dosage of either 1 g X 4 or 2 g X 2 per day, given to 10 and 14 male students, respectively, during two 5-day periods separated by a one week interval. The dosage of the plain formulation was maintained at 1 g X 4 daily in both parts of the investigation. Faeces were collected every 24 hours throughout the trial, covering a total of 4 weeks. Blood loss was measured using the 51Cr labelling technique. Acetard was found to cause statistically significantly less gastrointestinal blood loss as compared with the plain formulation, irrespective of whether Acetard was given twice or four times a day.

Adult↗
PubMed1990

Influence of paracetamol and acetylsalicylic acid on the toxicokinetics of toluene.

To study the influence of paracetamol and acetylsalicylic acid on the toxicokinetics of toluene, 2 groups of 10 male volunteers were exposed to toluene vapor (3.25 mmol/m3, 4 hr) at two different exposure occasions: toluene alone and toluene + analgesics. Solvent concentrations in blood and hippuric acid concentrations in urine were measured during the exposure period and 3 hr after exposure. The concentration of toluene in blood increased after ingestion of paracetamol or acetylsalicylic acid, as compared to the control exposure. The ingestion of paracetamol significantly increased the area under the blood concentration versus time curve (P less than 0.05) and the apparent blood clearance was significantly reduced (P less than 0.05) after ingestion of paracetamol but not after ingestion of acetylsalicylic acid. No statistically significant differences in the urinary excretion of hippuric acid were found.

Acetaminophen↗