Pentel P R, Asinger R W, Benowitz N L
Clin Pharmacol Ther. 1985 May;37(5):488-94. doi: 10.1038/clpt.1985.77.
Phenylpropanolamine (PPA) overdose can cause severe hypertension, intracerebral hemorrhage, and death. We studied the efficacy and safety of propranolol in the treatment of PPA-induced hypertension. Subjects received propranolol either by mouth for 48 hours before PPA or as a rapid intravenous infusion after PPA. PPA, 75 mg alone, increased blood pressure (31 +/- 14 mm Hg systolic, 20 +/- 5 mm Hg diastolic), and propranolol pretreatment antagonized this increase (12 +/- 10 mm Hg systolic, 10 +/- 7 mm Hg diastolic). Intravenous propranolol after PPA also decreased blood pressure. Left ventricular function (assessed by echocardiography) showed that PPA increased the stroke volume 30% (from 62.5 +/- 20.9 to 80.8 +/- 22.4 ml), the ejection fraction 9% (from 64% +/- 10% to 70% +/- 7%), and cardiac output 14% (from 3.6 +/- 0.6 to 4.1 +/- 1.0 L/min). Intravenous propranolol reversed these effects. Systemic vascular resistance was increased by PPA 28% (from 1710 +/- 200 to 2190 +/- 700 dyne X sec/cm5) and was further increased by propranolol 22% (to 2660 +/- 1200 dyne X sec/cm5). We conclude that PPA increases blood pressure by increasing systemic vascular resistance and cardiac output, and that propranolol antagonizes this increase by reversing the effect of PPA on cardiac output. That propranolol antagonizes the pressor effect of PPA is in contrast to the interaction in which propranolol enhances the pressor effect of norepinephrine. This is probably because PPA has less beta 2 activity than does norepinephrine.
苯丙醇胺(PPA)过量可导致严重高血压、脑出血及死亡。我们研究了普萘洛尔治疗PPA所致高血压的疗效及安全性。受试者在服用PPA前口服普萘洛尔48小时,或在服用PPA后快速静脉输注。单独使用75mg PPA可使血压升高(收缩压升高31±14mmHg,舒张压升高20±5mmHg),普萘洛尔预处理可拮抗这种升高(收缩压升高12±10mmHg,舒张压升高10±7mmHg)。PPA后静脉输注普萘洛尔也可降低血压。左心室功能(通过超声心动图评估)显示,PPA使每搏量增加30%(从62.5±20.9ml增至80.8±22.4ml),射血分数增加9%(从64%±10%增至70%±7%),心输出量增加14%(从3.6±0.6L/min增至4.1±1.0L/min)。静脉输注普萘洛尔可逆转这些效应。PPA使全身血管阻力增加28%(从1710±200达因·秒/厘米⁵增至2190±700达因·秒/厘米⁵),普萘洛尔使其进一步增加22%(增至2660±1200达因·秒/厘米⁵)。我们得出结论,PPA通过增加全身血管阻力和心输出量来升高血压,而普萘洛尔通过逆转PPA对心输出量的作用来拮抗这种升高。普萘洛尔拮抗PPA的升压作用与它增强去甲肾上腺素升压作用的相互作用相反。这可能是因为PPA的β₂活性比去甲肾上腺素低。