Antiinflammatory actions

Hydrocortisone and Prednisolone. Following the discovery of the antiinflammatory actions of cortisone (1) and cortisol (2), there was a need not only to develop highly efficient routes to the corticoids, but to discover novel stmctures with fewer side effects than those of the corticoids, eg, sodium and water retention, reduced carbohydrate tolerance (steroid diabetes), osteoporosis, and depressed host defense. 

Some of these indazoles showed analgesic activity greater than that of aspirin and several possessed significant antiinflammatory action. Both properties were the most striking and characteristic ones of the series. In a few cases the authors isolated the corresponding indazolones (705) which were less active than (704) in terms of analgesic and antiinflammatory properties. 

Several 2,3-disubstituted-4(3/f)quinazolinones were active against Plasmodium gallinaceum and showed antiinflammatory action on experimental edemas in animals. 6-(m-Amidinophenyldiazoamino)-... 

Replacement of the methyl ketone moiety in 78 by a phenyl sulfoxide, interestingly, leads to a relatively potent uricosuric agent with diminished antiinflammatory action. This effect in lowering serum levels or uric acid leads to the use of this drug in the treatment of gout. Alkylation of diethyl malonate with the chlorosulfide, 79, gives the intermediate, 80. The pyrazolodione (81) is prepared in the usual way by condensation with hydrazobenzene. Careful oxidation of the sulfide with one equiv-... 

I he potent antiinflammatory action exerted by many aryl acetic acid derivatives has led to the continued exploration of this class. It is apparent from a consideration of the structures of compounds that have become prominent that considerable structural latitude is possible without loss of activity. 

Acetaminophen is a nonsalicylate nonnarcotic analgesic whose mechanism of action is unknown. Lake the salicylates, acetaminophen has analgesic and antipyretic activity. However, acetaminophen does not possess antiinflammatory action and is of no value in the treatment of inflammation or inflammatory disorders. 

Corticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystalline steroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available The potent antiinflammatory action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders. The corticosteroids are discussed in Chapter 50. 

The efficacy of chitosan in the treatment of leg ulcers stems from its antiinflammatory action and stimulation of epithehahzation. Chitosans stimulate the granulation process and the epidermis formation, thus accelerating heahng, even in the elderly suffering from chronic venous insufficiency, the... 

It is used in the treatment of mild to moderate acne vulgaris and has comedolytic, keratolytic, and antiinflammatory action. 

Salicylic acid, sulfur, and resorcinol are second-line topical therapies. They are keratolytic and mildly antibacterial agents. Salicylic acid has comedolytic and antiinflammatory action. 

Acetaminophen has analgesic and antipyretic activity but little antiinflammatory action. It is highly hepatotoxic on overdose. 

Conti S, Costa B, CoUeoni M, Parolaro D, Giagnoni G, Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid... 

Pharmacology Topical corticosteroids exert an antiinflammatory action. Steroids inhibit inflammatory response to inciting agents of mechanical, chemical, or... 

Phenylbutazone (Butazolidin, Tandearil) (see Chapter 36) also displays antipyretic, analgesic, and antiinflammatory activity. In addition, it possesses some uricosuric potency and therefore is widely used for the treatment of acute attacks of gouty arthritis, in which it is about equal to colchicine in effectiveness. Although the drug does promote the renal excretion of uric acid, its usefulness is generally attributed to its antiinflammatory actions. 

CS057 Sagesaka, Y. M., T. Uemura, Y. Suzuki, CS068 T. Sugiura, M. Yoshida, K. Yamaguchi and K. Kyuki. Antimicrobial and antiinflammatory actions of tea-leaf sapo-... 

It acts peripherally by inhibiting the synthesis of prostaglandins by reversible inhibition of cyclooxygenase. Inhibition of the migration of leukocytes to an inflammatory site and inhibition of the release of lysosomal enzymes may also be involved in the antiinflammatory action. 

It is a para-amino phenol derivative, acts on CNS to produce analgesia and antipyretic effect. It has negligible antiinflammatory action peripherally in therapeutic uses. It is poor inhibitor of PG synthesis in peripheral tissues, but more active on COX in brain. It also raises the pain threshold. 

Drugs useful are indomethacin, piroxicam or naproxen. Their usefulness is due to strong antiinflammatory action and can be continued for 3-4 weeks. They also inhibit chemotactic migration of leukocytes into the affected joint. 

The bronchi have a rich parasympathetic innervation but there is no sympathetic innervation of bronchial smooth muscle and all sympathetic effects are due to circulating adrenaline (epinephrine and noradrenaline (norepinephrine) acting on (32 adrenoceptors. Stimulation of these receptors mediates bronchodilatation by relaxation of bronchial smooth muscle. Beta-adrenoceptor agonists also have limited antiinflammatory actions. They inhibit mediator release from mast cells and may stimulate... 

Chloroquine and hydroxychloroquine are used mainly in malaria (see Chapter 52) and in the rheumatic diseases. The mechanism of the antiinflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals. 

At higher dosage, methotrexate may cause bone marrow depression, megaloblastic anemia, alopecia, and mucositis. At the doses used in the treatment of inflammatory bowel disease, these events are uncommon but warrant dose reduction if they do occur. Folate supplementation reduces the risk of these events without impairing the antiinflammatory action. 

Clinical use Phenidine (Clissold, 1986) is a weak analgesic and antipyretic compound without antiinflammatory action. It has been used in combination with other compounds like aspirin, caffeine or codeine, but due to hematological and nephrotoxic side-effects (Dubach et al., 1983) has been withdrawn from many markets. 

Martel, R. R., Demerson, C.A., Humber, L.G., Philipp, A.H., Etodolic acid and related compounds. Chemistry and antiinflammatory actions of some potent di- and trisubstituted 1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids, J. Med. Chem. 1976, 19, 391-395. 

Rhen T, Cidlowski JA. 2005. Antiinflammatory action of glucocorticoids - new mechanisms for old drugs. NEJM. 353 1711-1723. 

Grzanna R, Lindmark L, Frondoza CG. Ginger— an herbal medicinal product with broad antiinflammatory actions. J Med Food. 2005 8 125-132. 

Copper complexes are the principal antiinflammatory agents under investigation at the moment39,40, although elsewhere in this review one or two other chelates are also discussed. The mechanisms by which copper complexes exert antiinflammatory action are no doubt numerous. However, it has been shown that some low molecular weight complexes dismute superoxide (O )41,42. ... 

LoVerme, J., Fu, J., Astarita, G., La Rana, G., Russo, R., Calignano, A., and Piomelli, D. (2005). The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the antiinflammatory actions of palmitoylethanolamide. Mol. Pharmacol. 67, 15—29. 

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