Reduced survival after isoprenaline/dopamine in d,l-propranolol intoxicated rats.
1. Respiratory and cardiovascular failure are principle toxic effects of beta-blocker overdose. Respiratory arrest is the primary cause of death in beta-blocker intoxicated rats. 2. The effect of beta-adrenoceptor agonists on respiratory and cardiovascular failure in beta-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg-1 h-1) intoxication in spontaneously breathing rats. 3. Neither the aselective, hydrophilic beta-agonist isoprenaline (10, 25, 50 micrograms kg-1 min-1), nor the beta 1-selective, lipophilic beta-agonist flerobuterol (1, 3, 10 microgram kg-1 min-1) and the beta 2-selective, lipophilic beta-agonist clenbuterol (10, 25, 50 micrograms kg-1 min-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats. 4. Isoprenaline (10 micrograms kg-1 min-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l-propranolol intoxicated rats either. 5. Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decreased in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6. Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.
Toet
A E
AE
National Poison Control Centre, Bilthoven, The Netherlands.
te Biesebeek
J D
JD
Vleeming
W
W
Wemer
J
J
Meulenbelt
J
J
de Wildt
D J
DJ
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000506:poisoning*; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011041:Poisoning / Q000188:drug therapy / Q000401:mortality; D011433:Propranolol / Q000008:administration & dosage / Q000506:poisoning*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D005934:Glucagon; D011433:Propranolol; C071321:flerobuterol; D007545:Isoproterenol; D000420:Albuterol; D004298:Dopamine; D002976:Clenbuterol