Tucker G T, Bax N D, Lennard M S, Al-Asady S, Bharaj H S, Woods H F
Br J Clin Pharmacol. 1984;17 Suppl 1(Suppl 1):21S-28S. doi: 10.1111/j.1365-2125.1984.tb02424.x.
In theory, beta-adrenoceptor antagonists could lower the clearance of free lignocaine in three ways (a) by decreasing hepatic blood flow, (b) by competing for plasma binding sites or (c) by inhibiting the enzymes responsible for metabolising lignocaine. The first mechanism has been demonstrated for propranolol and is probably common to all agents lacking intrinsic sympathomimetic activity. The second mechanism is discounted by data showing that propranolol, one of the more highly bound beta-adrenoceptor antagonists, does not alter the free fraction of lignocaine in plasma. In vitro studies support the third mechanism for the more lipid-soluble beta-adrenoceptor antagonists, as does the fact that observed decreases in the clearance of lignocaine in vivo are generally greater than the anticipated maximum lowering of hepatic blood flow.
理论上，β-肾上腺素能受体拮抗剂可通过三种方式降低游离利多卡因的清除率：(a) 减少肝血流量；(b) 竞争血浆结合位点；(c) 抑制负责代谢利多卡因的酶。第一种机制已在普萘洛尔中得到证实，可能是所有缺乏内在拟交感活性的药物所共有的。第二种机制已被数据排除，这些数据表明，结合度较高的β-肾上腺素能受体拮抗剂之一普萘洛尔不会改变血浆中利多卡因的游离分数。体外研究支持了脂溶性更高的β-肾上腺素能受体拮抗剂的第三种机制，体内观察到的利多卡因清除率下降通常大于预期的肝血流量最大降低幅度这一事实也支持了该机制。
