Pharmacological and toxicological properties of Ã-agonists

R.F. Wiykamp

Pharmacological and toxicological properties of Ã-agonists

in Residues of Veterinary Drugs and Mycotoxins in Animal Products

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R.F. Wiykamp

R.F. Wiykamp Department of Veterinary Basic Sciences, Division Pharmacology, Pharmacy and Toxicology, Utrecht University, P.O. Box 80176, 3508 TD Utrecht, The Netherlands

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Art:: Kapitel

Seiten:: 113â123

DOI:: https://doi.org/10.1163/9789004684171_018

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Summary

This paper focuses on the pharmacodynamic and pharmacokinetic aspects of Ã(2)adrenergic agonists, with special emphasis on their use in food-producing species. Therapeutic indications of Ã2-agonists in these animals are obstructive pulmonary disorders and tocolysis. However, several of them are illegally used as repartitioning agents. For this purpose, the dose is ten times higher than that used for therapeutic reasons. The mechanism of action of Ã2-agonists and some aspects of the relation between structure and activity are discussed. It is believed that the Ã-agonists which are currently the most frequently used as repartitioning agents (clenbuterol, salbutamol, mabuterol, mapenterol, bromobuterol etc.) principally act on muscle tissue. Lipolysis seems to be a secondary effect. However, there is important progress in the development of 63-agonists. These compounds more selectively stimulate 6-receptors present on brown adipose tissue, leading to lipolysis. Significant differences exist in the pharmacokinetic properties and biotransformation routes of Ã2-agonists. The compounds used as repartitioning agents possess a good oral bioavailability and a relatively long plasma-halflife. Conjugation with a sulphate is an important metabolic route for salbutamol, whereas the clenbuterol analogues are metabolized into several products, mainly resulting from side-chain cleavage and oxidation. The implications for human health of the use of Ã-agonists as repartitioning agents are not clear. Some cases have been described of consumers who developed signs of intoxication after eating meat (liver) contaminated with clenbuterol. Dose and withdrawal time are major determinants. In Europe, there is an considerable opposition from the side of the consumers. However, the development of more specific Ã2 and Ã3-agonists as repartitioning agents is continuing.

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Residues of Veterinary Drugs and Mycotoxins in Animal Products

New Methods for Risk Assessment and Quality Control

ISBN:: 9789004684171

Verleger:: Wageningen Academic

Print-Publikationsdatum:: 01 Jan 1996

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Pharmacological and toxicological properties of Ã-agonists

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Residues of Veterinary Drugs and Mycotoxins in Animal Products

New Methods for Risk Assessment and Quality Control

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Pharmacological and toxicological properties of Ã-agonists