Nonsteroidal anti-inflammatory drug pharmacology

In addition to their beneficial effects, some medications may actually cause cellular injury and disease. An example of this phenomenon involves nonsteroidal anti-inflammatory drugs (NSAIDS). These drugs include aspirin (a derivative of salicylic acid), ibuprofen (arylpropionic acid, Advil ), and acetaminophen (para-aminophenol derivative, Tylenol ). Because of their beneficial pharmacological effects, consumption of these agents has increased significantly in recent years. NSAIDS have the ability to treat fever, pain, acute inflammation, and chronic inflammatory diseases such as arthritis. They are also used prophylactically to prevent heart disease, stroke, and colon cancer. 

The compound 5-[5-(4-chlorophenyl)furan-2-yl]-2,3,4,5-tetrahydrofuran-2-one (F-1044, 7.85) is a nonsteroidal anti-inflammatory agent possibly acting via a ring-opened hydroxybutyric acid metabolite. To examine this hypothesis, F-1044 was submitted to extensive in vivo testing, which revealed potent activities and a unique pharmacological profile markedly different from that of acidic nonsteroidal anti-inflammatory drugs [169], These results have been interpreted to mean that part or most of the observed effects of F-... 

Proton pump inhibitors (PPIs), such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, are commonly prescribed to treat symptoms of heartburn, acid reflux, chest pain, dyspepsia, and chronic cough. PPIs inhibit the transfer of protons into the stomach lumen. Pharmacological acid suppression is thus used to treat gastroesophageal reflux disease (GERD) and esophagitis, peptic ulcers, and Helicobacter pylori infection as well as to prevent ulcer development with concurrent nonsteroidal anti-inflammatory drug use. 

Pharmacology Nonsteroidal anti-inflammatory drugs have analgesic, antipyretic, and anti-inflammatory activities. Major mechanism is believed to be inhibition of cyclooxygenase activity and prostaglandin synthesis. 

Murray M.D. and D.C. Brater (1993). Renal toxicity of the nonsteroidal anti-inflammatory drugs. Annual Reviews of Pharmacology and Toxicology 32 435 65. 

Figure 8.9 Prostaglandins and leukotrienes are potent eicosanoid lipid mediators, derived from phospholipase-released arachidonic acids, that are involved in numerous homeostatic biological functions and inflammation. They are generated by cyclooxygenase isozymes and 5-lipoxygenase, respectively, and their biosynthesis and pharmacological actions are inhibited by clinically relevant nonsteroidal anti-inflammatory drugs.

Basic and Clinical Pharmacology > Chapter 36. Nonsteroidal Anti-Inflammatory Drugs, Disease-Modifying Antirheumatic Drugs, Nonopioid Analgesics, Drugs Used in Gout > ... 

The enzymatic enantioselective hydrolysis of esters of naproxen and ibuprofen has attracted considerable attention because the (S)-enantiomers of these nonsteroidal anti-inflammatory drugs (NSAIDs) are the pharmacologically active isomers. These reactions have been successfully performed in a range of ionic liquids (Figure 10.10) [60, 65, 121]. 

Summary of nonsteroidal anti-inflammatory drugs.1 Described in Pharmacology update, p. 466. (Continued on next page.)... 

Schlienger RG, Jick H, Meier CR, Schlienger RG, Jick H, Meier CR. Use of nonsteroidal anti-inflammatory drugs and the risk of first-time acute myocardial infarction. British Journal of Clinical Pharmacology 2002 54 327-332. 

Chay S, Woods W E, Nugent T E et al 1982 The pharmacology of nonsteroidal anti-inflammatory drugs in the horse flunixin meglumine (Banamine). 

Dunn M J. Simonson M, Davidson E W et al 1988 Nonsteroidal anti-inflammatory drugs and renal function. Journal of Clinical Pharmacology 28 524-529... 

Goodrich L R, Furr M O, Robertson J L et al 1998 A toxicity study of eltenac, a nonsteroidal anti-inflammatory drug, in horses. Journal of Veterinary Pharmacology and Therapeutics 21 24-33... 

Garcia, M.L., Tost, D., Vilageliu, J., Lopez, S., Carganico, G. Mauleon, D. (1998) Bioavailability of S(+)-ketoprofen after oral administration of different mixtures of ketoprofen enantiomers to dogs. Journal of Clinical Pharmacology, 38, 22S-26S. Hayball, P.J. Meffin, P.J. (1987) Enantioselective disposition of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs. III. Fenoprofen disposition. Journal of Pharmacology and Experimental Therapeutics, 240, 631-636. 

All compounds of the test dataset are nonsteroidal anti-inflammatory drugs (NSAIDs) and are thus relatively similar in terms of their pharmacological properties (Fig. 18). The compounds are 1, acetylsalicylic acid 2, diclofenac 3, flufe-namic acid 4, flubiprofen 5, ibuprofen 6, indometacin 7, ketoprofen 8, meclofe-namic acid 9, mefenamic acid 10, naproxen 11, piroxicam 12, sulindac sulfide (active metabolite of sulindac) 13, tenoxicam 14, meloxicam 15, cgp 28238 16, DuP-697 17, L-745-337 18, 6-methoxy-2-naphthylacetic acid (active metabolite of nabumeton) 19, NS-389 20, SC 58125. 

After women have tried lifestyle changes, nutritional supplements, and nonpharmacologic treatment approaches, some may require pharmacologic therapies if there is limited response. Women with less severe PMS generally self-treat headaches and cramps with aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAlDs). NSAIDs, such as naproxen and ibuprofen, are the treatments of choice for dysmenorrhea, menstrual headaches or migraines, and mastalgia. 

Thun MJ, Henley J, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents Mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 2002 94 252-266. 

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