Aspirin

Contraindications

• Aspirin should be avoided by those known to be allergic to ibuprofen or naproxen.

• Caution should be exercised in those with asthma or NSAID-precipitated bronchospasm.

• It is generally recommended that one seek medical help if symptoms do not improve after a few days of therapy.

• Caution should be taken in patients with kidney disease, peptic ulcers, mild diabetes, gout or gastritis; manufacturers recommend talking to one's doctor before using this medicine.

• Taking aspirin with alcohol or warfarin increases the chance of gastrointestinal hemorrhage (stomach bleeding).

• Children under the age of 12 are discouraged from using aspirin to control cold or influenza symptoms as this has been linked with Reye's syndrome.

• Patients with hemophilia or other bleeding tendencies should not take salicylates.

• Some sources recommend that patients with hyperthyroidism avoid aspirin because it elevates T4 levels.

• Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency (G6PD), particularly in large doses and depending on the severity of the disease.

• People living in tropical-weather countries should discontinue use while symptoms or suspicion of Dengue Fever exist, due to an irreversible syndrome relating aspirin and that disease.

Adverse effects

Gastrointestinal complaints

Aspirin can cause blood loss. Delaney  studied that when aspirin is combined with other anticoagulants (an agent that prevents blood clots from forming) it can lead to great risk of gastrointestinal bleeding. Patients 18 years of age or above were chosen from the United Kingdom Research Database from 2000 to 2005. Out of 4,028 cases of gastrointestinal bleeding 53% had used a combination of over the counter drugs (2007). When using a combination of drugs there is 1 to 8 chance of increasing your risk of complaints if an antiplatelet (inhibits clots to form) and anticoagulants are taken together.

Undetected blood loss may lead to chromic anemia. Blood loss is associated with chronic use of aspirin.  This study first performed on animals, mainly rats, was also proved by patients who reported cases of blood loss ceasing when aspirin is not in use and anemia reoccurring when aspirin use is continued (1986).

Abdominal pain, such as dyspepsia, is an upper gastrointestinal symptom caused by aspirin. A study by Eisen proved that the incidence of abdominal pain was caused by anti-inflammatory drugs, such as aspirin (2005). The study was performed over a twelve week period with patients 18 or older. At 2, 6 and 12 weeks patients reported to study sites for safety assessments. Here the adverse effects were recorded as mild, moderate or severe (2005). About 21% of those using NAIDs (low dose aspirin) complained of dyspepsia.

Aspirin can cause heartburn. At a Coronary Care Unit blood samples were taken from acetylsalicylic acid (aspirin) using patients.  Gastrointestinal complaints were reported in 160 users which were eligible for the study. Heartburn was a complaint reported by 22% of the 160 aspirin users (2005).

To avoid gastrointestinal complaints take aspirin in an enteric coated form. The difference between enteric coated aspirin and regular microencapsulated aspirin is their effects.  104 participants were given a 14 day trial on the different types of aspirin being tested. After day 14 the dosage was lowered and reductions in gastric effects were seen in those with the enteric coated aspirin (1999).

Severe gastrointestinal complaints require discontinuation of aspirin to recover.214,846 patients using one or more NAIDs a day were recorded and observed. The data showed that in one year 4.8 incidents of gastrointestinal bleeding (UGIB) hospitalizations occur per every 1000 people who use NAIDS. Also only 1.2 UGIB hospitalizations occur per every 1000 non-users of NAIDs (2002).

Central effects

Large doses of salicylate or salicylic acid, a compound in aspirin, produces hearing loss in humans. When this chemical is released into the body it blocks the prestin (the motor protein in the outer hairs of the ear). 112 rats were conditioned to respond to a stimulus of a 10 kHz tone. Over a four day period they were injected daily with either saline (a solution used as a plasma substitute) or 300mg/kg of salicylate. These injections were given two hours before the test period. By the fourth day the results indicated that the rats receiving saline did not show any results of hearing loss, in fact they improved their response to the sound. On day one they had a hearing score of 87%, day two 90% and on day four they received a hearing score of 88% (2003). However, the rats in the salicylate group decreased in their hearing ability over the four day period. On day one they were at a 91% positive response rate, on day two 83% and day four they had a response rate of 79%. The degree of sensitivity and frequency selectivity of the cochlea (spiral structure in inner ear containing tiny hairs whose movement is recognized by the brain as sound) is due to the active mechanism generated by the outer layer hair cells. They induce a nonlinearity of the cochlea that can be easily recorded by a sensitive microphone placed in the ear canal. Cumulative injections of salicylate decreased the amplitude in the ear canal. This leads up to the disappearance of the noise on the third and fourth days of the experiment (2003).

Large doses of salicylate or salicylic acid, the active component in aspirin, causes tinnitus in humans.(42) In normal conditions, before the drug is released in the body, the arachidonic acid, fatty acid, is completely metabolized in the cochlea by the process of a group of enzymes called cyclooxygenase. Salicylate decreases the amounts of some of these enzymes and increases the others. Arachidonic acid increases in the ear channel, which causes the cochlear receptors to dysfunction, resulting in a ringing or blurry sound. In the experiment 112 rats were used, weighing between 80-120 grams. The rats were trained to respond to a conditioned sound stimulus. The rats were conditioned to a 10 kHz tone and the control group, which was 10 of the 112 rats were conditioned to a 4 kHz tone which when they heard it they would jump on to the climbing pole in their test box. Once conditioned the rats were tested for 9 consecutive days (2003). The rats received injections daily for four days of either saline alone, 300mg/kg of salicylate, or 35 mg/kg of mefanamate, which was used for treatment. The injections were given two hours before the unconditioned response was measured. The animals in the saline group showed no change in false positive responses. The animals in the salicylate group showed a significant increase in the number of false positive responses. On the fourth day there were 6 times as many false positive responses than on the first day (2003). This means the rats jumped even when it was silent, resulting in tinnitus because they were hearing a ringing even though the sound wasn’t being projected.

Pediatrics

Reye's syndrome can occur when children or pediatric patients are given aspirin for a fever or other illnesses or infections. Rogers  studied 213 patients under the age of 18 who were reported for Reye syndrome from the nationwide Reye's syndrome surveillance system. Out of 213 patients 211 had known that had another antecedent illness: 89% reported being ill (severe vomiting, mental strain, respiratory illness, vericella or gastrointestinal illness) two weeks before onset of Reye's syndrome (1985). Salicylate levels, the active acid in aspirin, were present in 162 of the 213 patients.

Reye's syndrome is due to fatty deterioration of liver cells. In a study done by Rogan 12 livers were obtained from children who had died from Reye’s syndrome and then one liver for the control from a child who had accidentally died. The autopsy stated that seven of the 12 livers had micro vesicular fatty change was present (1985).

The fatality rate of Reye's syndrome is 35% (43). A study used the nationwide Reye's syndrome surveillance system to find voluntary cases of patients with Reye's syndrome eligible for this study (1985). The surveillance year goes from December 1 to November 30. 213 cases were reported out of 43 states across the United States. Out of the 213 patients, 200 were reported for short term outcome. Out of the 200, 70 died. This makes the fatality rate 35% (1985).

Other effects

Aspirin causes prolonged bleeding after operations for up to 10 days. Thirty patients were observed after their various surgeries. Twenty of the thirty patients had to have an additional unplanned operation because of postoperative bleeding.This diffuse bleeding was associated with aspirin alone or in combination with another NSAID in 19 out of the 20 who had to have another operation due to bleeding after their operation. The average recovery time for the second operation was 11 days (1996).

High doses of aspirin for long-term treatment for arthritis or rheumatic fever increase liver enzymes causing liver damage without any symptoms. Yuen  states that an analysis was taken of 12 patients who were diagnosed with influenza A virus. The patients were given liver-function tests and six of the patients showed evidence of liver dysfunction.

Aspirin can induce angioedema. Angioedema appeared 1-6 hours after ingesting an aspirin in the patients participating in the study (2004). However, when the aspirin was taken alone it did not cause angioedema. The aspirin was either taken in combination with another NSAID-induced drug when angioedema appeared.

Bronchospasm is likely in children with chronic asthma if they were aspirin users.Twenty nine patients with asthma from the Chest and Asthma Clinic of the Royal Alexandra Hospital for Children participated in a study (1984). They were given symptom scores which they recorded activity through the day and night. The medication was given twice daily over a three week period. Then throughout the three weeks their diets were changed to make sure there was no interference with the aspirin and so the possible chronic ingestion wouldn’t occur. Bronchospasm is likely in 21% of these children if they continue to use aspirin because the study group had an incidence of hypersensitivity (1984).

Interactions

Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride have been known to enhance the intoxicating effect of salicyclates, and alcohol also enhances the gastrointestinal bleeding associated with these types of drugs as well. Aspirin is known to displace a number of drugs from protein binding sites in the blood, including the anti-diabetic drugs tolbutamide and chlorpropamide, the immunosuppressant methotrexate, phenytoin, probenecid, valproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism) and any nonsteroidal anti-inflammatory drug. Corticosteroids may also reduce the concentration of aspirin. The pharmacological activity of spironolactone may be reduced by taking aspirin, and aspirin is known to compete with Penicillin G for renal tubular secretion.Aspirin may also inhibit the absorption of vitamin C.