Nonsteroidal anti-inflammatory agent

Pain episodes usually can be managed at home. Hospitalized patients usually require parenteral analgesics. Analgesic options include opioids, nonsteroidal anti-inflammatory agents, and acetaminophen. The patient characteristics and severity of the crisis should determine the choice of agent and regimen. 

Amphotericin B is the mainstay of treatment of patients with severe endemic fungal infections. The conventional deoxycholate formulation of the drug can be associated with substantial infusion-related adverse effects (e.g., chills, fever, nausea, rigors, and in rare cases hypotension, flushing, respiratory difficulty, and arrhythmias). Pre-medication with low doses of hydrocortisone, acetaminophen, nonsteroidal anti-inflammatory agents, and meperidine is common to reduce acute infusion-related reactions. Venous irritation associated with the drug can also lead to thrombophlebitis, hence central venous catheters are the preferred route of administration in patients receiving more than a week of therapy. 

Class I compounds have both good solubility and permeability and generally offer no problems with regard to having a good absorption profile (e.g., acetaminophen, disopyramide, ketoprofen, metoprolol, nonsteroidal anti-inflammatory agents, valproic acid, verapamil). In general, one would not expect the presence of food to influence the absorption of this class... 

Nonsteroidal anti-inflammatory agents are used extensively as nonprescription drugs, and residues of these compounds have been detected ubiquitously in WWTP effluents at the pg L 1 levels, and they also frequently occur at the ng L 1 level in the aquatic environment (see [2], this volume). As a result, many researchers have focused on the degradation of these pharmaceuticals, which are one of the most studied groups of therapeutic agents in terms of fungal transformation. 

While N-oxidation is essentially driven by FMO, it is not true of S-oxidation. As indicated earlier, P450 can contribute significantly to S-oxidation and, in some cases, it is the dominant or even only enzyme catalyzing the reaction. Sulindac sulfide, a metabolite of the nonsteroidal anti-inflammatory agent, sulindac, is reoxidized by FMO (71) with a high degree of stereoselectivity toward the (7 )-enantiomer back to enantiomerically... 

Metabolic pathways rarely lead to breaking a carbon-carbon bond however, there are exceptions such as the conversion of the prodrug nabumetone to an active nonsteroidal anti-inflammatory agent as shown in Figure 4.84 (153). Although the mechanism of this conversion is unknown, if oxidation leads to two adjacent carbonyl groups it weakens the carbon-carbon bond and further oxidation leads the rupture of this bond. 

The first oxidation product of a sulfide is a sulfoxide and this can be further oxidized to a sulfone (Fig. 4.91). A good example is sulindac, which is a sulfoxide. It can be reduced to a sulfide or oxidized to a sulfone (Fig. 4.91). The sulfide is more active as a nonsteroidal anti-inflammatory agent than the parent drug but the sulfone is inactive (160). 

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-... 

A very interesting comparison between methyl and OV,/V-dicthylcarba-moyl)methyl prodrug benzoates of nonsteroidal anti-inflammatory agents... 

Management of an acute attack of gout involves the use of high doses of nonsteroidal anti-inflammatory agents (NSAIDs). Colchicine is useful in patients with heart failure where the use of NSAIDs is contraindicated because of water retention. Allopurinol and other uricosuric agents are not indicated for acute attacks as they may aggravate the condition. The use of an intra-articular corticosteroid injection in gout is unlicensed. 

Drugs that are subject to enterohepatic cycling are, therefore, excreted slowly. Pertinent examples include digi-toxin and acidic nonsteroidal anti-inflammatory agents (p. 200). 

Many drugs are racemates, including 13-blockers, nonsteroidal anti-inflammatory agents, and anticholinergics (e.g benzetimide A). A racemate consists of a molecule and its corresponding mirror image which, like the left and right hand, cannot be superimposed. Such chiral ( handed ) pairs of molecules are referred to as enantiomers. Usually, chirality is due to a carbon atom (C) linked to four different substituents ( asymmetric center ). Enantiomerism is a special case of stereoisomerism. Non-chiral stereoisomers are called diaster-eomers (e.g., quinidine/quinine). 

Acetaminophen differs from the nonsteroidal anti-inflammatory agents described in that it is devoid of anti-inflammatory and antirheumatic properties. It was recently shown that acetaminophen, like aspirin, inhibits cyclooxygenase action in the brain and is even stronger than aspirin. On the other hand, the mechanism of analgesic action of acetaminophen is not fully clear, since it acts poorly on peripheral cyclooxygenase. 

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