[Atracurium and vecuronium: interaction with three orally administered calcium antagonists in animal experiments]

Interactions between calcium antagonists (CA) and muscle relaxants have been reported however due to the extremely high dosages of CA used in these studies, the clinical relevance of the observed interactions has been questioned. In order to simulate clinical practice--which entails long-term oral treatment and significant reductions in systolic blood pressure--CA were administered to rats orally (by gavage) for 8 days at a dosage that induced a systolic blood pressure decrease of not more than 25 +/- 5 mmHg. Ten groups of six male Sprague-Dawley rats each, body weight (BW) 313 +/- 23 g, were subjected to oral administration of three different CA: nitrendipine (1 mg/kg BW), nisoldipine (1 mg/kg BW), and diltiazem (100 mg/kg BW) or their solvents (control) three times daily by gavage for a period of 8 days. One hour after the last dose of drug or solvent, the rats were anesthetized (pentobarbital 60 mg/kg BW) and mechanically ventilated via tracheostomy. Monitoring included rectal temperature, carotid artery pressure, central venous pressure, heart rate, blood gases, and end-tidal CO2. Evoked train-of-four (T4) twitch tension of the right tibialis anterior muscle was recorded continuously. After equilibration of vital signs and muscle twitch tension, vecuronium (150 micrograms/kg BW) or atracurium (500 micrograms/kg BW) was injected into the internal jugular vein four times at 5-min intervals after twitch tension had totally recovered and T4 fade had disappeared. Twitch depression, duration 90, and onset time of neuromuscular block in CA-pretreated animals were compared to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)