4- Nonsteroidal anti-inflammatory drugs

Anti-inflammatory drugs have a special, if not pivotal, place in the history of Western medicine and drug therapy and in the birth and evolution of the pharmaceutical industry. From at least the time of early Chinese and Egyptian civilizations over 5,000 years ago, humans sought plants and other natural materials for the relief of the four signs of inflammation— redness, heat, swelling, and pain. We know that as early as 400 BC, the Greek physician Hippocrates advocated the use 

Baldo and N.H. Pham, Drug Allergy Clinical Aspects, Diagnosis, Mechanisms, Structure-Activity Relationships, DOI 10.1007/978-l-4614-7261-2 9, Springer Science+Business Media, LLC 2013 

Nonsteroidal anti-inflammatory drugs are widely used in veterinary practice and are, therefore, of growing interest to the residue control of animal-derived food. Veterinarians are seeing an increased use of anti-inflammatory agents, administered with or without antibiotics, for treatment of mastitis because of the increase in efficiency of these agents over antibiotics alone. 

Little information is available regarding tissue distribution or metabolic products of nonsteroidal anti-inflammatory drugs in cattle. The early synthetic compounds were simple derivatives either of salicylic acid such as acetylsalicylic acid and methylsalicylic acid, or of pyrazolone such as metamizole, oxyphenbuta-zone, phenylbutazone, propylphenazone, and suxibuzone. Modern nonsteroidal anti-inflammatory drugs are derivatives either of anthranilic acid such as dido- 

Acetylsalicylic acid is readily absorbed from the gastrointestinal tract in dogs, cats, and swine due to its ionization suppression by the stomach acid. In the more alkaline small intestine, the large surface area for absorption makes up for the increased ionization of the drug and rapid absorption continues. In contrast, absorption is slower from the rumen in cattle. 

The plasma half-life of acetylsalicylic acid varies from 0.8 h in the ruminant to 37.5 h in the cat. This is due partly to the very short elimination in cattle, which is 10 times more rapid in cattle than in most other animals. The clearance is also very high in cattle. 

Methylsalicylic acid, unlike acetylsalicylic acid, is nearly exclusively used as an external rubifacient drug for painful muscles or joints and distributed as ointments or liniments due to their irritating effects on the gastrointestinal mucosa. Absorption through intact skin is possible and has led to prosecution following detection in race-horse urine. 

Aspirin (many trade names) Ketoprofen (Orudis, others) 

Cortisone (Cortone acetate) Prednisolone (Prelone, others) 

Dexamethasone (Decadron, others) Prednisone (Deltasone, others) 

Flydrocortisone (Cortef, others) Triamcinolone (Aristocort, others) 

For the second building block, the enol acetate derived from nopinone is oxidised with lead tetraacetate. A Michael reaction and subsequent Wagner-Meer-wein rearrangement finally yield the active compound. 

The history of non-steroidal anti-inflammatory drugs (NSAlDs) dates right back to ancient times - beginning with Hippocrates of Kos (460-377 BC) and the collection of medical writings known as the Corpus Hippocraticum. It is therefore as old as medical science itself. Hippocrates aheady knew of the pain-relieving (analgesic) and fever-reducing (antipyretic) effects of willow bark (Fig. 5.70). 

71 Meadowsweet (Fillpendula ulmaria). For its essential oils, the blossoms of this plant were formerly used to produce mead, a fermented brew similar to beer. 

72 Like Frederick the Great (left), Charles V, Fienry VIII (right) and Albrecht Wenzel Eusebius von Wald stein (Wallenstein, a Bohemian military leader and politician) also suffered from rheumatism and gout. It is fair to assume that they made use of willow bark and meadowsweet, in order to treat their minor ailments or rheumatic pain , as gout was popularly called. 

As a result of his observations of Nature, Edward Stone (1702-1768), a curate from Chipping Norton in Oxfordshire, used willow bark in 1763 to treat more than 50 patients with malaria. In 1792, the physician Samuel James (1763-1831) used the bark of goat willow (or pussy-willow , Salix caprea) to reduce fever. Stones work first found general recognition in Nicholas Culpeper s Complete Herbal, in the edition of 1802, and willow bark was acknowledged thereafter as 

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The Molecular Basis for the Action of Nonsteroidal Anti-inflammatory Drugs... 

R J. Hayball, Chirality and nonsteroidal anti-inflammatory drugs. Drugs, 1996, 52 (Suppl. 5), 47-58. 

CHAPTER 18 Nonnarcotic Analgesics Nonsteroidal Anti-inflammatory Drugs (NSAlDs)... 

The Patient Receiving a Nonsteroidal Anti-inflammatory Drug... 

The salicylates and nonsteroidal anti-inflammatory drug (NSAIDs) are important in the treatment of arthritic conditions. For example, the salicylates and NSAIDs are used in the treatment of rheumatoid arthritis (a chronic disease characterized by inflammatory changes within the body s connective tissue) and osteoarthritis (a noninflammatory joint disease resulting in degeneration of the articular cartilage and... 

Chapter 18 Non narcotic Analgesics Nonsteroidal Anti-Inflammatory Drugs... 

Like aspirin, ibuprofen is a nonsteroidal anti-inflammatory drug. It is a cyclooxygenase inhibitor that interferes with COX-1 and COX-2 forms of that enzyme. Its effects on COX-2 give it fever-reducing (antipyretic), analgesic (pain relief), and anti-inflammatory functions. 

Orthoformates have been used in the lipase-catalyzed esterification aimed at the kinetic resolution of racemic acids such as flurbiprofen, a nonsteroidal anti-inflammatory drug (Figure 6.18). Orthoformates trap the water as it is formed through hydrolysis, and therefore prevent the reverse reaction, and, at the same time, provide the alcohol for the esteriflcation [65]. 

We do not discontinue use of any of the patient s medications including anticoagulants, aspirin or nonsteroidal anti-inflammatory drugs. Systemic isotretinoin (Acutane) is considered to be a contraindication to any external treatment of the skin. We feel that the minimal... 

Zembowicz A, Mastalerz L, Setkowicz M, Radzis-zewski W, Szczeklik A Safety of cyclooxygenase-2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs. Arch Dermatol 2003 139 1577-1582. 

CHAN T A, MORIN p J, VOGELSTEIN B and KINZLER K w (1998) Mechanisms rmderlying nonsteroidal anti-inflammatory drug-mediated apoptosis , Proc Natl Acad Sci USA, 95, 681-6. 

Photodegradation of the nonsteroidal anti-inflammatory drug diclofenac produced carbazole-l-acetate as the major product (Figure 1.12) (Moore et al. 1990). In a lake under natural conditions, it was rapidly decomposed photochemically though none of the products produced in laboratory experiments could be detected (Buser et al. 1998). 

NSAID nonsteroidal anti-inflammatory drug o organic phase OCT (oct) -octanol p peak... 

Recognize differences between ulcers induced by Helicobacter pylori (HP) and nonsteroidal anti-inflammatory drugs (NSAIDs) in terms of risk factors, pathogenesis, signs and symptoms, clinical course, and prognosis. 

H2RA, histamine2-receptor antagonist NSAID, nonsteroidal anti-inflammatory drug PPI, proton pump inhibitor. (Adapted from Berardi RR, Welage LS. Peptic ulcer disease. In DiPiro JT, Talbert RL,... 

Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med 1999 340 1888-1899. 

Most patients treated with either interferon or pegylated interferon experience flulike symptoms (fevers, chills, rigors, and myalgias). These symptoms may be mild to moderate in severity and usually occur with the first injection and diminish as the treatment continues. The flulike symptoms may be minimized by premedication with acetaminophen or a nonsteroidal anti-inflammatory drug. 

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