Anti-inflammatory steroids are natural (cortisone) or synthetic (prednisone, dexamethasone) glucocorticoids. They are anti-inflammatory due to their inhibition of phospholipase A2, blocking the production of the substrate for cyclooxygenase action and by blockage of the induction of cyclooxygenase 2. However, as discussed in Chapter 10, glucocorticoids have many other physio logical functions and their use, particularly long term, is therefore limited because of many untoward side effects.

Cyclooxygenase inhibitors are among the most commonly used drugs in the world. Aspirin (acetyl-salicylic acid) has been used to treat fever, pain, and inflammation for over a century, i.e., since long before the discovery of prostaglandins. As the role of PGs in these processes began to come clear, the role of aspirin as an inhibitor of PG production emerged and it became the founding member of what would be the nonsteroidal anti-inflammatory drugs (NSAIDs) which now include several other drugs, examples of which are shown in Figure 1A. Aspirin is unique among these drugs in irreversibly inactivating COX-1 through acetylation of the active site while the other drugs block the access of arachidonic acid to it.

Fig1. Cyclooxygenase inhibitors. The structures of some commonly used nonspecific nonsteroidal anti-inflammatory drugs (NSAIDS) are shown in panel A. These compounds inhibit both COX-1 and COX-2. B. Two examples of specific COX-2 inhibitors are shown. Celecoxib is currently on the market while Rofecoxib was withdrawn in 2005.

Because they inhibit COX-1, which functions in many tissues and physiological systems, the side effects of nonspecific NSAIDs are considerable. Among the most serious are the effects on the gastrointestinal system so that using them to treat chronic pain and inflammation as in arthritis, for example, can lead to potentially life-threatening ulcers and bleeding. Other side effects include kidney and liver damage. Thus when COX-2, an enzyme induced upon inflammation, was discovered in 1989, there was much excitement about the possibility of inhibiting this enzyme selectively, thus avoiding gastrointestinal side effects. This is especially important in treating the pain and inflammation of chronic diseases such as rheumatoid arthritis.

The difference in the size of the active site mentioned above is the basis for some of the selectivity of the drugs between the two enzymes. Some of these drugs, shown in Figure 1B, have led to increased thrombolytic and adverse cardiovascular events and it is now clear that developing and prescribing these drugs has become more complex than originally anticipated. While there is still interest in COX-2 selective inhibitors for certain applications, attention has shifted somewhat to the specific synthases in an effort to pin point more precisely the active molecule that is being targeted.

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للشروع بصيانتها وترميمها..متحف الكفيل يستلم الدفعة الرابعة من مقتنيات العتبة العسكرية المقدسة

على مدار اليوم.. قسم الشؤون الدينية يقدّم خدماته التبليغية والإرشادية خلال شهر رمضان المبارك

شعبة التوجيه الديني تنظّم مسابقة ميدانية بذكرى ولادة الإمام الحسن المجتبى (عليه السلام)

قسم التطوير يقيم سلسلة من الورش التدريبية عن الأمن السيبراني لملاكاته

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الآخبار الصحية

مركب طبيعي في القهوة يحمينا من التهابات اللثة

داء السكري لا يرفع السكر فقط.. بل يزيد خطر الإصابة بأمراض القلب!

اكتشاف سبب غير متوقع لضعف الذاكرة والتركيز

نصائح علمية لتقوية دماغك وتقليل التدهور العقلي

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الآخبار التكنلوجية

باحثون يرصدون أثر تغيّر المناخ في دم البشر

الجميع يحلم.. لماذا يتذكر البعض أحلامهم بينما ينسى آخرون؟

حرق الأمونيا.. كيف يساعد محطات الكهرباء في اليابان على إزالة الكربون؟

الشمس تقذف نتوءا عملاقا باتجاه قطبها الشمالي

المزيد

مواضيع ذات صلة

Examples of Biological Actions of Prostaglandins

Prostaglandin H Synthase/ Cyclooxygenase

Phospholipase A2

Overview of Eicosanoid Synthesis

Structure and Nomenclature of Eicosanoids

Water is an Excellent Nucleophile

Interaction with Water Influences the Structure of Biomolecules

Fibrin Clots Are Dissolved by Plasmin

The Activity of Antithrombin, an Inhibitor of Thrombin, Is Increased by Heparin

Conversion of Fibrinogen to Fibrin Is Catalyzed by Thrombin

Factor Xa Leads to Activation of Prothrombin to Thrombin

Most Transmembrane Proteins Have Membrane Spanning α Helices