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Clin Toxicol (Phila) ; 51(4): 208-15, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23530458

RESUMO

BACKGROUND: Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. METHOD: Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG - QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. RESULTS: ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). CONCLUSION: Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.


Assuntos
Amitriptilina/intoxicação , Antidepressivos Tricíclicos/intoxicação , Sistema Cardiovascular/efeitos dos fármacos , Modelos Animais de Doenças , Overdose de Drogas/terapia , Emulsões Gordurosas Intravenosas/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Administração Oral , Amitriptilina/administração & dosagem , Amitriptilina/sangue , Amitriptilina/farmacocinética , Animais , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/sangue , Antidepressivos Tricíclicos/farmacocinética , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Overdose de Drogas/sangue , Overdose de Drogas/fisiopatologia , Emulsões/efeitos adversos , Emulsões/uso terapêutico , Emulsões Gordurosas Intravenosas/uso terapêutico , Coração/efeitos dos fármacos , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Absorção Intestinal , Masculino , Fosfolipídeos/efeitos adversos , Fosfolipídeos/uso terapêutico , Projetos Piloto , Distribuição Aleatória , Ratos , Ratos Wistar , Óleo de Soja/efeitos adversos , Óleo de Soja/uso terapêutico , Análise de Sobrevida
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