Drugs chemical modification

Further chemical modification of the phenylpiperidine moiety has proven unusually fruitful in producing medicinal agents that affect the central nervous system. First, a series of compounds loosely related to the reversed meperidines produced several drugs with important antipsychotic activity. Further discussion of this pharmacologic activity, often referred to as major tranquilizer activity, will be found in the section on phenothiazines. The group led by Janssen took advantage of the chemistry of the... 

The hundreds of different pharmaceutical agents approved for use by the U.S. Food and Drug Administration come from many sources (see the Chapter 5 Focus On). Many drugs are isolated directly from plants or bacteria, and others are made by chemical modification of naturally occurring compounds, but an... 

Those drugs that come from natural sources, either directly or after chemical modification, are usually chiral and are generally found only as a single enantiomer rather than as a racemic mixture. Penicillin V, for example, an antibiotic isolated from the Pemcillimti mold, has the 2S,SR,6R configuration. Its enantiomer, which does not occur naturally but can be made in the laboratory, has no antibiotic activity. 

The elimination of a drug is its removal from the body, either by chemical modification through metabolism or by removal from the body through the kidney, the gut, the lungs or the skin. 

Over the past few years there have been an increasing number of reports of diseases that are becoming resistant to previously effective drug treatments. This resistance is often due to the presence of enzymes that bring about chemical modification of the drug to an inactive form, e.g. /S-lactamase enzymes deactivate (6-lactam antibiotics by their conversion to penicillanic acid. 

The effect of various chemical modifications on the mechanical properties of reconstituted collagen and the diffusion rates of the steroid medroxyprogesterone was investigated (38). Formaldehyde-treated films, which are heavily crosslinked, have high moduli and low rates of drug release. Films treated with chrome quickly become hydrated in solution and have low moduli and very rapid drug release characteristics. 

In order to improve the properties of the well-known adrenergic antagonist, two chemical modulations on classical drugs including NO-donor moiety have been described. On the one hand, chemical modifications on Prazosin, an a 1-adrenergic antagonist, including furoxanyl moieties have been reported [70,182,183]. hi this approach, the 2-furanylcarbonyl moiety of Pra-... 

Improvement of the properties of a drug may be achieved by the chemical modification of the parent drug. The preparation of an ester, salt, or other modification of the parent structure may be employed with parenteral drugs to increase stability, alter drug solubility, enhance depot action, avoid formulation... 

The most serious disadvantage of the prodrug approach to controlled sustained delivery is that extensive development must be undertaken to find the correct chemical modification for a specific drug. Additionally, once a prodrug is formed, it is a new drug entity and, therefore, requires extensive and costly studies to determine safety and efficacy. 

The system is relatively independent of the physicochemical properties of the drug (i.e., it does not require chemical modifications). 

V. J. Stella, T. J. Mikkelson, and J. D. Pipkin, Pro-drugs The control of drug delivery via bioreversible chemical modification, in Drug Delivery Systems Characteristics and Biomedical Applications (R. L. Ju-liano, ed.), Oxford University Press, New York, 1980,... 

VHL Lee. (1993). Improved ocular drug delivery by use of chemical modification (prodrugs). In P Edman, ed. Biopharmaceutics of Ocular Drug Delivery. Boca Raton, FL, CRC Press, pp 121-143. 

In addition to chemical-based drugs, a range of pharmaceutical substances (e.g. hormones and blood products) are produced by/extracted from biological sources. Such products, some major examples of which are listed in Table 1.2, may thus be described as products of biotechnology. In some instances, categorizing pharmaceuticals as products of biotechnology or chemical synthesis becomes somewhat artificial. For example, certain semi-synthetic antibiotics are produced by chemical modification of natural antibiotics produced by fermentation technology. 

Most of the antiemetic clinical trials in the last decade have involved metoclopramide (1) either as a single agent or in combination with other drugs. Similarly, most of the chemical modification studies have been designed to optimize antiemetic and/or gastroprokinetic properties of metoclopramide and to eliminate undesirable CNS side-effects which are the consequence of its dopamine D2 receptor blockade [1-3]. 

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