Fields of application

Typical areas of application for Aspirin® are

Pain
Headaches
Migraine
Fever
Flu

Aspirin® also has a blood-thinning effect. The reason for this is an inhibition of blood platelets or thrombocytes. These normally stick together at the beginning of blood clotting and thus create the first clot.

However, for this to happen, they must be activated by several signal substances. These include the so-called Thromboxan A2. Aspirin inhibits the enzyme COX 1, which is required for the formation of thrombboxan A2.

The inhibition is irreversible. Thrombocytes are not able to form new COX 1, so that the inhibition persists for a longer period of time. Ibuprofen or diclofenac only inhibit the COX enzymes reversibly and are therefore not used for long-term anticoagulation.

Aspirin® can also be used to treat migraine. It has been shown to be particularly effective against migraine-related headaches. It is important to take Aspirin® at an early stage of a migraine attack.

In the course of migraine, disturbances of the gastrointestinal tract can occur, which can impair the absorption of the active substance. For this reason, Aspirin® should be taken with sufficient water, especially in migraine attacks. This probably facilitates the passage through the stomach.

Aspirin® is particularly effective for mild to moderate migraine attacks. In the treatment of headaches, the pain-relieving effect of Aspirin® is mainly used. The correct dosage is important here.

While too low doses (e.g. 100 mg) do not provide sufficient pain relief, too high doses can lead to stronger adverse effects. Aspirin® has been in use for years in its effect against headaches and is therefore well tested. Side effects occur mainly when high doses are taken regularly.

An intake for the treatment of acute headaches is therefore relatively low in side effects. Exceptions to this are for example hypersensitivity reactions. Theoretically, Aspirin® in sufficient doses is also effective against the headaches typically associated with a hangover.

This has even been proven in studies. However, it should be noted that both alcohol and Aspirin® can damage the stomach lining if taken frequently. In general, Aspirin® as a hangover remedy should not be taken prophylactically, i.e. before a party. There is little to be said against taking it once for a very severe hangover, but regular use can cause severe adverse effects.

Mode of action

The pain-inhibiting effect of Aspirin® is based on the inhibition of the formation of messenger substances (so-called mediators), which are responsible for the transmission of the pain stimulus from the site of damage to the brain. Although pain itself is a reaction to tissue damage, it is ultimately a sensation produced by the brain (more precisely: by the central nervous system, CNS, which includes the spinal cord and the brain). Pain is therefore a reaction of the body’s own, whose function is to provide the body with a “warning signal”.

Pain requires treatment if it goes beyond the normal level, lasts too long (chronic pain, phantom pain) or is very excruciating. From a medical point of view, pain is the result of an inflammatory process, i.e. the body’s natural response to the penetration of pathogens, foreign substances or the destruction of tissue. The messenger substances known as prostaglandins, whose formation is inhibited by Aspirin®, cause the unpleasant symptoms typical of an inflammation in the body: Damaged tissue turns red as a result of increased blood flow (hyperemia) and dilation of the vessels (vasodilatation).

The tissue swells because, on the one hand, cell fluid is released as a result of the cell damage and, on the other hand, because of the increased permeability of the vessels (permeability), which is intended to allow the immune cells circulating in the blood to migrate into the tissue. Among the four classic characteristics of inflammation, already known in ancient times, is the overheating of the tissue in the vicinity of the injury. Last but not least, the messenger substances are responsible for creating the pain impression.

The formation of the signal substances takes place in immune cells, especially in white blood cells (the so-called leukocytes, from Greek leukos = white). Attracted and activated by foreign bodies or pathogens, the white blood cells in turn release messenger substances themselves in order to activate further immune cells and recruit them to the site of the event. This phenomenon is called chemotaxis.

Aspirin® intervenes in this process by inhibiting the most important enzyme required by the immune cells to form the messenger substances, cyclooxygenase (COX for short). Chemically speaking, the acetylsalicylic acid contained in Aspirin® as the active ingredient acetylates the cyclooxygenase, which is thereby permanently, i.e. irreversibly, inactivated. It is important to note that this enzyme occurs in two different forms in the body: COX 1 is present in all body cells and performs important (life) functions there: It promotes the formation of mucus and alkaline bicarbonate, which protects the sensitive mucous membrane of the stomach from the aggressive hydrochloric acid needed for digestion.

ASA also inhibits the enzyme phospholipase A2, which is responsible for the release of the fatty acid arachidonic acid from phospholipids and is an important precursor in the synthesis of prostaglandins. It also directly reduces hydrochloric acid production. The blood circulation-promoting effect also contributes to the protection of the gastric mucosa, as cell-damaging radicals can be removed in the bloodstream.

A further, desired effect of COX 1 is the promotion of the blood circulation in the kidney. The prostaglandins formed by the enzyme are responsible for all the positive effects of COX 1 mentioned above. The preventive use against embolism in myocardial infarction patients is based on the presence of COX 1 in blood platelets (thrombocytes): there, the enzyme helps to form the blood clotting promoting thrombboxes.

By inhibiting COX 1, coagulation in the body is thus inhibited. A related enzyme, cyclooxygenase 2, called Cox 2, is only present in specialised inflammatory cells and only comes into action when it is activated by the inflammatory messengers. Aspirin® is also known as an “unselective COX inhibitor” because it cannot distinguish between the two forms of cyclooxygenase.

More recent painkillers have been developed specifically to inhibit only COX 2, so that the desired function of COX 1 is retained. These new drugs are called “Coxibe”. Some examples of selective COX 2 inhibitors are melecoxib, which is the prototype but in practice has no fewer side effects than conventional analgesics, and rofecoxib (better known by the trade name Vioxx.

The drug was withdrawn from the market as a precautionary measure, as a clinical study showed an increase in side effects in the cardiovascular system. It is now considered certain that this risk could be minimized by the simultaneous administration of Aspirin® in low doses or another antiplatelet agent. Parecoxib (trade name: Dynastat) is the first injectable COX-2 selective drug, which is therefore used for the treatment of postoperative pain.

The formation of prostaglandins by COX-2 can also occur in the central nervous system. The cell messengers (not permanently active, but), for example, formed by cytotoxins, bacterial components or similar foreign substances of immune cells, set off a cascade of different reactions, the end point of which is the formation of fever-inducing substances (these are called endogenous, i.e. coming from within, “pyrogens”). The fever-inducing substances are the trigger for the formation of prostaglandin in the brain (for those interested: the formation takes place in a structure adjacent to the hypothalamus (region in the brain) called organum vasculosum laminae terminalis, or OVLT for short).

The prostaglandins cause the temperature balance in the hypothalamus to be misregulated: The body raises the desired standard temperature (the set point), which manifests itself as a fever, i.e. a state of elevated body temperature. Again by inhibiting the prostaglandin synthesis, Aspirin® therefore has a strong antipyretic effect. In addition to its analgesic, antipyretic and anti-inflammatory effect, another property of Aspirin® is used in medicine: By inhibiting cyclooxygenase, it also inhibits the production of a messenger substance required for blood coagulation by promoting platelet aggregation – thromboxane, which is chemically related in structure to prostaglandins (see above) and belongs to the eicosanoids.

It also directly reduces the production of hydrochloric acid. The blood circulation-promoting effect also contributes to the protection of the stomach mucosa, since cell-damaging radicals can be removed in the bloodstream. A further, desired effect of COX 1 is the promotion of the blood circulation in the kidney.

The prostaglandins formed by the enzyme are responsible for all the positive effects of COX 1 mentioned above. The preventive use against embolism in myocardial infarction patients is based on the presence of COX 1 in blood platelets (thrombocytes): there, the enzyme helps to form the blood clotting promoting thrombboxes. By inhibiting COX 1, coagulation in the body is thus inhibited.

A related enzyme, cyclooxygenase 2, called Cox 2, is only present in specialised inflammatory cells and only comes into action when it is activated by the inflammatory messengers. Aspirin® is also known as an “unselective COX inhibitor” because it cannot distinguish between the two forms of cyclooxygenase. More recent painkillers have been developed specifically to inhibit only COX 2, so that the desired function of COX 1 is retained.

These new drugs are called “Coxibe”. Some examples of selective COX 2 inhibitors are melecoxib, which is the prototype but in practice has no fewer side effects than conventional analgesics, and rofecoxib (better known by the trade name Vioxx. The drug was withdrawn from the market as a precautionary measure, as a clinical study showed an increase in side effects in the cardiovascular system.

It is now considered certain that this risk could be minimized by the simultaneous administration of Aspirin® in low doses or another antiplatelet agent. Parecoxib (trade name: Dynastat) is the first injectable COX-2 selective drug, which is therefore used for the treatment of postoperative pain. The formation of prostaglandins by COX-2 can also occur in the central nervous system.

The cell messengers (not permanently active, but), for example, formed by cytotoxins, bacterial components or similar foreign substances of immune cells, set off a cascade of different reactions, the end point of which is the formation of fever-inducing substances (these are called endogenous, i.e. coming from within, “pyrogens”). The fever-inducing substances are the trigger for the formation of prostaglandin in the brain (for those interested: the formation takes place in a structure adjacent to the hypothalamus (region in the brain) called organum vasculosum laminae terminalis, or OVLT for short). The prostaglandins cause the temperature balance in the hypothalamus to be misregulated: The body raises the desired standard temperature (the set point), which manifests itself as a fever, i.e. a state of elevated body temperature. Again by inhibiting the prostaglandin synthesis, Aspirin® therefore has a strong antipyretic effect. In addition to its analgesic, antipyretic and anti-inflammatory effect, another property of Aspirin® is used in medicine: By inhibiting cyclooxygenase, it also inhibits the production of a messenger substance required for blood coagulation by promoting platelet aggregation – thromboxane, which is chemically related in structure to prostaglandins (see above) and belongs to the eicosanoids.