Metabolization

What happens to Aspirin® in the body? Aspirin® is taken orally, i.e. as a tablet. The absorption into the blood starts in the stomach, which explains the early onset of action compared to other analgesics: the highest concentration in the blood is reached after only 25 minutes.

The reason for this is the chemical structure of Aspirin® as an acid, which is responsible for accumulation in the mucous membrane cells of the stomach. Due to its own acidic character, Aspirin® is present in the likewise acidic environment of the gastric mucosa to a higher degree in its non-charged form (i.e. chemically: it is less dissociated), which is able to cross the cell membrane and accumulate in the gastric mucosa cell. In the cell interior, on the other hand, which is naturally not acidic but has a more neutral pH value of 7, Aspirin® is present more strongly as a charged particle (i.e. as an ion) that cannot penetrate the cell membrane.

This principle of trapping charged particles within cells is also called “ion trap” and explains not only the early onset of action but also the strong undesirable effects of Aspirin® in high doses. After being absorbed from the stomach and intestines, Aspirin® is processed into its breakdown products by the enzymes of cell metabolism. A not inconsiderable proportion of 30% is already being metabolized before Aspirin® could develop its effect as a COX-inhibitor, so that only the remaining 70% is responsible for the desired analgesic, antipyretic and anti-inflammatory effect.

This not 100% “bio-availability” must be taken into account when dosing aspirin. Within the scope of metabolism, salicylic acid, which also acts as a COX-inhibitor, is first formed. It is not broken down as quickly as Aspirin®, which is already half eliminated after 15 minutes, and thus ensures that the effect of Aspirin® lasts longer than would be expected after its presence in the blood. The salicylic acid itself remains in the blood for a long time (half of it is still detectable after 30 hours), especially when high doses of Aspirin® have been administered, until it is excreted directly via the kidneys in the urine, and is partly converted by the liver into end products that are easier to excrete.

Side effects

The most important side effects of Aspirin® are gastrointestinal complaints: It can lead to reflux, heartburn and nausea, in more severe cases to erosions (superficial injuries of the stomach lining) and ulcers (deeper epithelial defects that reach into the muscles and can even break through (rupture) to the outside. Another consequence is an increase in bleeding time due to the inhibition of thromboxane synthesis. The increased occurrence of asthmatic complaints after taking Aspirin® led to the term “analgesic asthma”.

This form of asthma accounts for about 10 % of all patients suffering from asthma, but only occurs when the predisposition (predisposition) is right, i.e. when there is an increased sensitivity to the messenger substances known as leukotrienes, which are related to prostaglandins (see above). (The leukotrienes are messenger substances which are formed from the same basic substance as the prostaglandins – arachidonic acid consisting of twenty carbon atoms. The messenger substances formed from arachidonic acid are therefore called “eikosanoids”, from Greek eikos = twenty).

This parent substance of the prostaglandins is available in increased quantities in cyclooxygenase inhibition. Therefore, when Aspirin® is taken, more leukotrienes are formed at the same time (a leukotriene shift takes place). Asthma, a respiratory disease characterized by narrowing of the bronchial tubes, is based on precisely this effect of leukotrienes, i.e.

spasms, i.e. sudden, violent contractions of the bronchial muscles. These manifest themselves as the main symptom of asthma, i.e. the attacks of shortness of breath, which typically occur with a strong trigger. The treatment of this side effect consists in turn in the administration of drugs that inhibit the effect (in this case not the formation) of leukotrienes by blocking the point of attack of the messenger substance on the body cells (the receptor): An example of this is montelukast (trade name: Singulair), also known as a “leukotriene antagonist” according to its mechanism of action.

One of the rarer side effects of Aspirin® is Reye’s syndrome, the cause of which is still unknown. It occurs exclusively in children up to the age of 15 who are treated for a viral infection accompanied by fever (e.g. chickenpox). Reye’s syndrome is a very severe clinical picture associated with symptoms such as vomiting, fever and drowsiness.

It can lead to coma with a fatal outcome in 25 to 50% of patients. One of the rarer side effects of Aspirin® is Reye’s syndrome, the cause of which is still unknown. It occurs exclusively in children up to the age of 15 who are being treated for a viral infection accompanied by fever (e.g. chickenpox).

Reye’s syndrome is a very severe clinical picture associated with symptoms such as vomiting, fever and drowsiness. It can lead to coma with a fatal outcome in 25 to 50% of patients. Aspirin® usually relieves headaches.

However, headaches can sometimes occur while taking Aspirin®. This is probably a side effect. The exact causes are still relatively unexplored.

It should also be noted that continuous use of excessive amounts of painkillers can lead to a so-called medication overuse headache, for short. This is a chronic headache. Diarrhoea can also occur as a side effect of Aspirin®.

The intestinal movement is influenced by so-called prostaglandins, among other things. These are also formed by the enzymes COX 1/2. Aspirin® inhibits this prostaglandin formation.

This also affects the control of the intestinal movement, possibly leading to diarrhoea. Diarrhoea is one of the more harmless gastrointestinal side effects. A doctor should be consulted if blood is added to the diarrhoea.

Since Aspirin® mainly damages the stomach lining, long-term use can lead to dangerous bleeding. If there is bleeding in the upper part of the gastrointestinal tract, the blood is altered by the gastrointestinal passage. This leads to the so-called tar stools.

This is a black coloration of the stool, which can often be accompanied by diarrhea. A doctor should be consulted immediately. Besides the non-bloody diarrhoea, nausea is one of the most common side effects of the gastrointestinal tract when taking Aspirin®.

As with most side effects of Aspirin®, nausea often occurs with long-term use of high doses. However, it is also possible that corresponding side effects occur with the first intake. Since everyone can react slightly differently to different medications such as Aspirin®, some people complain of nausea quickly, while others take Aspirin® for months without being affected.