Antirheumatic effects

Oxyphenbutazone (712), y-hydroxyphenylbutazone and kebuzone (715) are metabolites of phenylbutazone in liver. The first cited is an equally potent antiinflammatory agent but slightly less toxic. Compounds (711) and (712) are rarely used as analgesics and antipyretics because of their toxicities. The first one is used in therapy of rheumatoid disorders characterized by a lack of detectable antiglobulin and antinuclear antibodies in the serum. The y-hydroxyphenylbutazone has marked uricosuric activity but little antirheumatic effect. Kebuzone (715) is an antiinflammatory agent still widely used in Europe. 

Sulfasalazine use is often limited by adverse effects. Antirheumatic effects should be seen in 2 months. 

Azathioprme is a purine analog that is converted to 6-mercaptopurine and is thought to interfere with DNA and RNA synthesis. Antirheumatic effects... 

Acetylsalicylic acid and related non-steroidal anti-inflammatory drugs (NSAIDs) selectively inhibit the cyclooxygenase activity of prostaglandin synthase [2] and consequently the synthesis of most eicosanoids. This explains their analgesic, antipyretic, and antirheumatic effects. Frequent side effects of NSAIDs also result from inhibition of eicosanoid synthesis. For example, they impair hemostasis because the synthesis of thromboxanes by thrombocytes is inhibited. In the stomach, NSAIDs increase HCl secretion and at the same time inhibit the formation of protective mucus. Long-term NSAID use can therefore damage the gastric mucosa. 

Pharmacology Salicylates have analgesic, antipyretic, anti-inflammatory, and antirheumatic effects. Salicylates lower elevated body temperature through vasodilation of peripheral vessels, thus enhancing dissipation of excess heat. The anti-inflammatory and analgesic activity may be mediated through inhibition of the prostaglandin synthetase enzyme complex. 

In certain instances, the body converts a drug to several active metabolites possessing dissimilar pharmacologic properties. For example, phenylbutazone undergoes aromatic hydroxylation to produce a metabolite that has sodium-retaining and antirheumatic activities, and also undergoes alkyl chain oxidation to produce a metabolite with a strong uricosuric property. Thus, phenylbutazone has both uricosuric and antirheumatic effects. 

Chamomile has been used medicinally since the time of ancient Rome for its purported sedative, antispasmodic, and antirheumatic effects. Today, it is used topically to treat a variety of inflammatory conditions involving the mouth, skin, respiratory tract (via inhalation), and gastrointestinal tract. It is also used internally as a gastrointestinal antispasmodic and an anti-inflammatory agent. Chamomile is believed to have sedative, hypnotic, analgesic, and immunostimulant effects. 

Sulfasalazine, a prodrug, is cleaved by bacteria in the colon into sulfapyridine and 5-aminosalicylic acid. It is believed that the sul-fapyridine moiety is responsible for the agent s antirheumatic properties, although the exact mechanism of action is not known. Once the colonic bacteria have cleaved sulfasalazine, sulfapyridine and 5-aminosalicylic acid are absorbed rapidly from the gastrointestinal tract. Sulfapyridine distributes rapidly throughout the body, but higher concentrations are found in certain tissues such as serous fluid, liver, and intestines. Both sulfasalazine and its metabolites are excreted in the urine. Antirheumatic effects should be seen within 2 months. 

Chamomile has been used medicinally since ancient Rome for its purported sedative, antispasmodic, and antirheumatic effects (Anonymous, 1991). 

The evidence in favour of a relationship between non-steroidal antirheumatic activity and the pituitary-adrenal system is based mainly on experiments involving salicylates and phenylbutazone. No attempt will be made to discuss these problems in detail since they have been adequately reviewed by Smith and Done for salicylates, and by Rechenburg for phenylbutazone. Smith argued persuasively that the available experimental evidence on salicylates does not support the view that they either mimic or reinforce the actions of the natural adrenocortical hormones, and that the similar clinical effects of salicylates and these steroids in rheumatic diseases must therefore be produced by different mechanisms. Done, on the other hand, suggests that the concept cannot be prematurely dismissed and believes that the possibility that salicylate simultaneously affects the production and disposition of adrenocortical hormones deserves further consideration. He emphasizes that the antirheumatic effects of salicylates are not dependent on the maintenance of elevated circulating levels of corticoids. 

In the U.S. double-blind study in which NSAID use was unrestricted, a dose-dependent increase in serum creatinine from baseline was observed. In contrast, although slight increases were seen in the Japanese study, most patients creatinine levels remained within the normal range. Whether the concomitant use of NSAIDs was a confounding factor in the development of increased creatinine is not clear. It is important to note that the antirheumatic effect of tacrolimus becomes clear within the first 4 weeks after treatment initiation and, therefore, the potential exists to reduce the dose of NSAIDs at that time. Further clinical studies are currently under way to confirm these results in a larger cohort of patients who have failed at least one DMARD in the United States and Japan, using a double-blind, placebo-controlled paradigm. This study should also better define the safety profile of tacrolimus in this patient population. 

The tricyclic antidepressants can delay the absorption of phenylbutazone and oxyphenbutazone from the gut, but their antirheumatic effects are probably not affected. 

The absorption of a single 400-mg dose of phenylbutazone in 4 depressed women was considerably delayed (time to maximum level, 4 to 10 hours compared with 2 hours), but the total amount absorbed (measured by the urinary excretion of oxyphenbutazone) remained unchanged when they were pretreated with desipramine 75 mg daily for 7 days. In another 5 depressed women the half-life of oxyphenbutazone was found to be unaltered by 75 mg of desipramine or nortriptyline dailyAnimal studies have confirmed that the absorption of phenylbutazone and oxyphenbutazone are delayed by the tricyclic antidepressants, probably because their antimuscarinic effects reduce the motility of the gut, - but there seems to be no direct clinical evidence that the antirheumatic effects of either drug are reduced by this interaction. No particular precautions appear to be needed. 

Chrubasik, S., W. Enderlein, R. Bauer, and W. Grabner. 1997. Evidence for antirheumatic effectiveness of Herba Urticae dio-icae in acute arthritis A pilot study. Phytomedicine 4(2) 105-108. Collier, H.O.J., and G.B. Chesher. 1956. Identification of 5-hydroxytryptamine in the sting of the nettle (Urtica dioica). Br. J. Pharmacol. Chemother. 11(2) 186. 

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