Anti-inflammatory refers to the body's own or therapeutic reduction of inflammation that does not remove the cause of the inflammation. Anti-inflammatory (synonym: antiphlogistic , anti-inflammatory ) acting drug hot anti-inflammatory drugs (Greek anti "against", phlogosis "inflammation") or anti-inflammatory drugs and in addition physical methods used in the treatment of inflammatory diseases, including as anti-inflammatory drugs . The most significant and strongest anti-inflammatory hormone is thatCortisol , which is released as part of the hypothalamus-pituitary-adrenal cortex axis in all forms of stress (physical and psychological, but also with hunger and infections).
Anti-inflammatory drugs in the narrower sense of the word are the COX inhibitors and glucocorticoids, whereby the COX inhibitors are compared to the glucocorticoids as non-steroidal anti-inflammatory drugs (or non-steroidal anti-inflammatory drugs , NSAIDs). All systemically acting anti-inflammatory drugs (with the exception of the COX inhibitors) weaken the body's own defense against pathogens.
The enzyme cyclooxygenase (COX) contributes to inflammation by catalyzing two reaction steps in the synthesis of inflammatory mediators from the class of prostaglandins . These inflammation mediators are responsible in particular for the increased sensitivity to pain in the inflammation area, from which the main effect of COX inhibitors as pain relievers results. The non-specific COX inhibitors include acetylsalicylic acid (ASA, for example as aspirin or Godamed ), ibuprofen , naproxen and diclofenac ( Voltaren ) and ketoprofen ; Newer drugs that selectively inhibit the isoform COX-2 are the coxibs . See also: Non-steroidal anti-inflammatory drug # classification .
Prostaglandins are also necessary for other processes in the body, in particular they protect the stomach from stomach acid and ensure adequate blood flow to the kidneys. In addition, the COX is necessary for the synthesis of thromboxane in the blood platelets (has a vasoconstricting and coagulation-promoting effect) and prostacyclin in vascular wall cells (has a vasodilator and anticoagulant effect). This results in the side effects of the unspecific COX inhibitors: ulcers in the stomach (gastric ulcer ) and intestine ( duodenal ulcer ), kidney damage and increased blood pressure, inhibition of platelet aggregation (the latter being the desired main effect in low doses of ASA). Since the isoform COX-2 is responsible for the inflammatory reaction, drugs have been developed which should be free from the above side effects by selectively blocking the COX-2. These hopes were not fulfilled. Although ulcers are somewhat rarer with the use of coxibs, more serious cardiovascular events occur because COX-2 is also of great importance in the kidneys and in the vascular wall cells.
Steroids are endogenous or synthetic substances that are chemically derived from cholesterol . These include the body's own stress hormone cortisol and other glucocorticoids , which increase blood sugar, but also have an immunosuppressive effect. The effect of synthetic glucocorticoids such as hydrocortisone , prednisolone or dexamethasone is based on the binding to the same receptors in the cell nucleus, which is why glucocorticoids are very well tolerated. Many autoimmune diseases progress in episodes, and short-term therapy with a high-dose glucocorticoid (shock therapy) often provides acute acute improvement. Long-term systemic use , on the other hand, is only possible in low doses, since the imposed stress metabolism would otherwise lead to Cushing's syndrome ; Therefore, other medications are often necessary for long-term basic therapy . The topical administration of glucocorticoids is widely used for the treatment of inflammatory skin diseases and usually without systemic side effects; depending on the region of the body, local side effects such as skin atrophy and telangiectasia can become relevant in the long term.
The steroid hormone calcitriol (activated vitamin D ) on the one hand inhibits T-cell reactions, but on the other hand promotes the activity and survival of macrophages , so that it cannot be generally described as immunosuppressive. Applied locally to the skin, calcitriol and derivatives such as calcipotriol are used in particular to treat psoriasis (psoriasis). Although vitamin D deficiency is discussed as a cause of autoimmune diseases, there is no recommendation for the oral intake of vitamin D supplements for the prevention or treatment of inflammatory diseases.
In addition to glucocorticoids, immunosuppressants also include a large number of other drugs with very different modes of action; the corresponding article provides an overview. The dermatologist will find many other options for local therapy of inflammatory skin diseases among the immunosuppressants. In rheumatology , immunosuppressants are used as long-term basic therapy . This prevents relapses and progression of the disease without having to take high doses of glucocorticoids over the long term; one also speaks of disease-modifying anti-rheumatic drugs (DMARD). Important representatives of this therapy principle are methotrexate (MTX), azathioprine , leflunomide , sulfasalazine and hydroxychloroquine .
Modern anti-inflammatory drugs
Modern anti-inflammatory drugs specifically intervene in the communication between immune cells . Messenger substances can be neutralized or their receptors on the cells can be blocked. Exemplary targets include the tumor necrosis factor , the interleukin-6 receptor or B-cell - antigen CD20 . Since the cell types and messenger substances involved differ for different inflammatory diseases, a more specific and thus stronger effect can be achieved through the targeted selection of a modern anti-inflammatory drug.
The inhibitors used are mostly proteins or other larger biopolymers ; they are often monoclonal antibodies , parts of antibodies or fusion proteins with antibodies. In clinical parlance, these drugs are referred to as biologics . Since proteins are easily digested when taken by mouth , infusions or injections under the skin are necessary, which are repeated at intervals of days to months. Since proteins can denature , biologicals must be stored in the refrigerator. The Janus kinase inhibitors are an example of new developments that work similarly to biologics, but are chemically small molecules so that they can be taken as a tablet.
Common to all modern anti-inflammatory drugs are the enormous (often five-digit) annual therapy costs. For this reason, their use is often limited to the failure of classical pharmacotherapies. In order to increase the effect, the approval often prescribes the combination with classic immunosuppressants such as MTX.
Cooling has a local anti-inflammatory effect by slowing down the metabolism, reducing the excitation of sensitized nociceptors and reducing blood flow. Constant cooling instead of short intervals is important in order to avoid reactive hyperthermia. For the patient, there is a decrease in the signs of inflammation, pain, redness and swelling; A surface temperature of 12 ° C to 13 ° C must be reached to ensure complete freedom from pain. In the case of persistent pain due to muscle tension (as with non-specific back pain ), however, heat is more suitable.
Inflammatory skin diseases often improve spontaneously in summer. One possible reason for this is that UV light is necessary for the body's own synthesis of vitamin D. However, UV light also has an acute anti-inflammatory effect on the irradiated skin, for which cytostatic effects are held responsible: The higher-frequency (more energetic) UV B radiation is for the most part already absorbed in the epidermis and causes direct DNA damage through strand breakage, while the Lower frequency (lower energy) UV A radiation penetrates into the dermis and generates reactive oxygen species . With targeted light therapy in dermatology, the frequency band is selected according to the disease to be treated and the intensity to protect against skin cancer is determined individually for the patient after measuring the minimum erythema dose . The effect can be increased by photosensitizing substances such as psoralens (see PUVA ).
The noticeable accumulation of autoimmune diseases in industrialized countries suggests a connection between modern lifestyles and inflammatory diseases, but the theories that have arisen have so far hardly led to evidence-based therapies. For example, it has been proven that rheumatoid arthritis can be improved by taking 5.5 g of fish oil per day; According to the underlying theory, a diet low in arachidonic acid reduces the formation of proinflammatory mediators through substrate deprivation, while a diet rich in eicosapentaenoic acid should promote the formation of anti-inflammatory mediators.
- Heinz Lüllmann, Klaus Mohr, Martin Wehling, Lutz Hein (eds.): Pharmacology and Toxicology . 18th edition. Georg Thieme Verlag, Stuttgart 2016, ISBN 978-3-13-368518-4 , Chapter 19.5 The Eicosanoid System and 19.6 Therapy of Rheumatic Diseases .
- Heinz Lüllmann, Klaus Mohr, Martin Wehling, Lutz Hein (eds.): Pharmacology and Toxicology . 18th edition. Georg Thieme Verlag, Stuttgart 2016, ISBN 978-3-13-368518-4 , p. 355 .
- Robert Franz Schmidt , Florian Lang, Manfred Heckmann (eds.): Physiology of humans . 31st edition. Springer Medizin Verlag, Heidelberg 2010, ISBN 978-3-642-01650-9 , p. 686 .
- Robert Franz Schmidt , Florian Lang, Manfred Heckmann (eds.): Physiology of humans . 31st edition. Springer Medizin Verlag, Heidelberg 2010, ISBN 978-3-642-01650-9 , p. 314 .
- German Pain Society eV (ed.): Basic book Q14 pain medicine . 2015, ISBN 978-3-00-051025-0 , pp. 63 .