Pharmacokinetics adrenoceptor antagonists

Cadralazine has been launched under the trade names cadraten and cadri-lan. Pharmacological, pharmacokinetic and clinical studies on it have been reviewed [212]. A once-daily dosage of 15 mg cadralazine has been shown to be effective in the treatment of mild to severe hypertension and to be well tolerated. The therapeutic efficacy and tolerability can be improved by combining cadralazine with a -adrenoceptor antagonist [212]. 

Drug interactions with beta-adrenoceptor antagonists can be pharmacokinetic or pharmacodynamic (383-385). 

Lennard MS, Tucker GT, Woods HF. The polymorphic oxidation of beta-adrenoceptor antagonists. Clinical pharmacokinetic considerations. Clin Pharmacokinet 1986 11(1) 1-17. 

Goldberg MR, Sciberras D, De Smet M, Lowry R, Tomasko L, Lee Y, Olah TV, Zhao J, Vyas KP, Halpin R, Kari PH, James I. Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HTib id agonist differential effects of propranolol, nadolol and metoprolol. Br J Qin Pharmacol 2001 52(l) 69-76. 

Silipo C and Vittoria A, Relationships between octanol-water partition data, chromatographic indices and their dependence on pH in a set of beta-adrenoceptor blocking agents, Farmaco, 45, 647-663 (1990). See also Hinderling PH, Schmidlin O and Seydel JK, Quantitative relationships between structure and pharmacokinetics of beta-adrenoceptor blocking agents in man, J. Pharmacokin. Biopharm., 12, 263-287 (1984). Taylor EA, Jefferson D, Carroll JD and Turner P, Cerebrospinal fluid concentrations of propranolol, pindolol, and atenolol in man Evidence for central actions of beta-adrenoceptor antagonists, Br. J. Clin. Pharmacol, 12, 549-559 (1981). NB See Pindolol for furdter details. 

Riddell JG, Harron DWG, Shanks, RG Clinical pharmacokinetics of j8-adrenoceptor antagonists An update. Clin. Pharmacoldnet. 1987 12 305-320. 

Jack DB, Kendall MJ, Dean S, Laugher SJ, ZamanR, TennesonME. The effect of Itydralazine on the pharmacokinetics of three different beta adrenoceptor antagonists metoprolol, nadolol, and acebutolol. Biopharm DnigDispos (1982) 3, 47-54. 

Silodosin is a selective ajA-adrenoceptor antagonist, which has been marketed for the treatment of benign prostatic hyperplasia. Its pharmacology, pharmacokinetics, efficacy, adverse effects, and drug interactions have been reviewed [94 ]. 

All the clinically available (J-blockers are competitive antagonists. Nonselective [3-blockers act at both (3 and (32 receptors, whereas car-dioselective ( -antagonists primarily block 3i receptors. These drugs also differ in intrinsic sympathomimetic activity, in central nervous system (CNS) effects, and in pharmacokinetics (Figure 7.5). Although all (3-blockers lower blood pressure in hypertension, they do not induce postural hypotension because the a-adrenoceptors remain functional therefore, normal sympathetic control of the vasculature is maintained. P-blockers are also effective in treating angina, cardiac arrhythmias,... 

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