Adrenoceptor agonists elimination

Tizanidine o -Adrenoceptor agonist in the spinal cord Presynaptic and postsynaptic inhibition of reflex motor output Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis Renal and hepatic elimination t duration, 3-6 h Toxicities Weakness, sedation hypotension... 

Fitting the data directly to either Equation 5.14 or Equation 5.15 eliminates bias in the data imposed by reciprocal linear curve fitting. Figure 5.21 shows the use of nonlinear curve fitting to measure the affinity of the a-adrenoceptor agonist oxymetazoline in rat anococcygeus muscle after alkylation of a portion of the receptors with phenoxybenzamine. This data shows how all three curves can be used for a better estimate of the affinity with nonlinear curve fitting, a technique not possible with the double reciprocal plot approach where only two dose-response curves can be used. The use of three curves increases the power of the analysis... 

Nix et al. (1990) found the protective effect of formoterol against methacholine-induced broncho-constriction in 12 asthmatic patients lasting for at least 5 h. The rapid pulmonary absorption of inhaled formoterol and its slow elimination from plasma are in agreement with the fast onset and the long duration, respectively, of bronchodilation of inhaled formoterol fumarate in clinical trials (Le-CAiLLON et al. 1997). There was no indication that formoterol produced a more pronounced tachyphylaxis to P2-adrenoceptor stimulation in the bronchial muscle of asthmatics than the P2-adrenoceptor agonists normally used, e.g. salbutamol (Larsson et al. 1988, Arvidsson et al. 1989). Formoterol powder is as potent as solution (Clauzel et al. 1991). 

The rebound phenomenon is plaiirly a potential hazard and the use of a p-adrenoceptor blocker in the presence of ischaemic heart disease would be safer if rebound could be eliminated, p-adrenoceptor blockers that are not pure antagonists but have some agonist (sympathomimetic ischaemic) activity, i.e. partial agonists, may prevent the generation of additional adrenoceptors (up-regulation). Indeed there is evidence that rebound is less or is absent with pindolol, a partial agonist P-adrenoceptor blocker. 

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