Digoxin for atrial fibrillation: good, but not too good: a case report / Digoxina para fibrilação atrial: boa, mas não muito: relato de caso

Digoxin is a cardiotonic glycoside that is traditionally used for the treatment of heart failure and atrial fibrillation in humans and animals. However, the use of digoxin is still a challenge in clinical practice due to its narrow therapeutic range and its potential interaction with several drugs, which could facilitate the development of toxicity. A 12-year-old Labrador retriever was referred with a clinical diagnosis of heart failure and atrial fibrillation, anorexia, vomiting, and diarrhea. He had been medicated with digoxin, furosemide, lisinopril, and amiodarone. The patient also showed clinical signs of hip osteoarthritis and received firocoxib for four days. He additionally received drugs for gastrointeritis. The electrocardiogram demonstrated atrial fibrillation and signs of digitalis toxicity. Laboratory examination showed a high concentration of plasma digoxin, and 5 days after withdrawal of the drugs, the symptoms disappeared, as did the digitalis effects seen in the previous electrocardiogram.(AU)

A digoxina é um glicosídeo cardiotônico tradicionalmente utilizado no tratamento de insuficiência cardíaca e fibri-lação atrial em humanos e animais. Porém, o uso da digoxina continua sendo um desafio na prática clínica devido a sua estreita faixa terapêutica, bem como a sua potencial interação com diversos fármacos, facilitando o desenvolvimento de toxicidade. Um Labrador Retriever de 12 anos de idade foi encaminhado com diagnóstico clinico de insuficiência cardíaca, apresentando fibrilação atrial, anorexia, vômitos e diarreia. Ele vinha sendo medicado com digoxina, furosemida, lisinopril e amiodarona. Ele havia sido concomitantemente medicado com firocoxibe por quatro dias para tratamento de osteoartrite coxo-femoral, além de medicamentos para gastroenterite. O eletrocardiograma demonstrou fibrilação atrial e sinais de toxicidade digitalica. O exame laboratorial revelou alta concentração de digoxina plasmática sendo que, cinco dias após a suspensão dos medica-mentos, o paciente já apresentava melhora clinica acentuada, enquanto os efeitos digitálicos observados no eletrocardiograma anterior desapareceram.(AU)

Activity of the antiarrhythmic drug amiodarone against Leishmania (L) infantum: an in vitro and in vivo approach

Background:Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market.Methods:In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.)infantum and its in vitro and in vivo activity.Results:The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR.Conclusions:Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.(AU)

Activity of the antiarrhythmic drug amiodarone against Leishmania (L) infantum: an in vitro and in vivo approach

Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. Methods: In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.)infantum and its in vitro and in vivo activity. Results: The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Conclusions: Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.(AU)

Reversible atrial fibrillation following Crotalinae envenomation

Abstract Background Cardiotoxicity is a documented complication of Crotalinae envenomation. Reported cardiac complications following snake envenomation have included acute myocardial infarction, electrocardiogram abnormalities and arrhythmias. Few reports exist describing arrhythmia induced by viper envenomation and to our knowledge none describe arrhythmia induced by Crotalinae envenomation. This report concerns the first known case of atrial fibrillation precipitated by rattlesnake bite. Case presentation A 73-year-old Caucasian man with a past medical history of hypertension, hyperlipidemia, type 1 diabetes mellitus, and a baseline first-degree atrioventricular block presented to the emergency department following a rattlesnake bite to his left lower leg. He developed pain and swelling in his left leg two-hour post-envenomation and subsequently received four vials of Crotalidae polyvalent immune fab (ovine). At three-hour post-envenomation following transfer to the intensive care unit, an electrocardiogram revealed new-onset atrial fibrillation. An amiodarone drip was started and the patient successfully converted to normal sinus rhythm approximately six hours after he was found to be in atrial fibrillation. A transthoracic echocardiogram revealed mild concentric left ventricular hypertrophy and an ejection fraction of 72%. He was discharged the following day with no hematological abnormalities and a baseline first-degree atrioventricular block. Conclusion This is the first documented case of reversible atrial fibrillation precipitated by Crotalinae envenomation. In patients with pertinent risk factors for developing atrial fibrillation, physicians should be aware of the potential for this arrhythmia. Direct toxic effects of venom or structural and electrophysiological cardiovascular abnormalities may predispose snakebite patients to arrhythmia, warranting extended and attentive cardiac monitoring.

Reversible atrial fibrillation following Crotalinae envenomation

Background Cardiotoxicity is a documented complication of Crotalinae envenomation. Reported cardiac complications following snake envenomation have included acute myocardial infarction, electrocardiogram abnormalities and arrhythmias. Few reports exist describing arrhythmia induced by viper envenomation and to our knowledge none describe arrhythmia induced by Crotalinae envenomation. This report concerns the first known case of atrial fibrillation precipitated by rattlesnake bite. Case presentation A 73-year-old Caucasian man with a past medical history of hypertension, hyperlipidemia, type 1 diabetes mellitus, and a baseline first-degree atrioventricular block presented to the emergency department following a rattlesnake bite to his left lower leg. He developed pain and swelling in his left leg two-hour post-envenomation and subsequently received four vials of Crotalidae polyvalent immune fab (ovine). At three-hour post-envenomation following transfer to the intensive care unit, an electrocardiogram revealed new-onset atrial fibrillation. An amiodarone drip was started and the patient successfully converted to normal sinus rhythm approximately six hours after he was found to be in atrial fibrillation. A transthoracic echocardiogram revealed mild concentric left ventricular hypertrophy and an ejection fraction of 72%. He was discharged the following day with no hematological abnormalities and a baseline first-degree atrioventricular block. Conclusion This is the first documented case of reversible atrial fibrillation precipitated by Crotalinae envenomation. In patients with pertinent risk factors for developing atrial fibrillation, physicians should be aware of the potential for this arrhythmia. Direct toxic effects of venom or structural and electrophysiological cardiovascular abnormalities may predispose snakebite patients to arrhythmia, warranting extended and attentive cardiac monitoring.(AU)

Reversible atrial fibrillation following Crotalinae envenomation

Background Cardiotoxicity is a documented complication of Crotalinae envenomation. Reported cardiac complications following snake envenomation have included acute myocardial infarction, electrocardiogram abnormalities and arrhythmias. Few reports exist describing arrhythmia induced by viper envenomation and to our knowledge none describe arrhythmia induced by Crotalinae envenomation. This report concerns the first known case of atrial fibrillation precipitated by rattlesnake bite. Case presentation A 73-year-old Caucasian man with a past medical history of hypertension, hyperlipidemia, type 1 diabetes mellitus, and a baseline first-degree atrioventricular block presented to the emergency department following a rattlesnake bite to his left lower leg. He developed pain and swelling in his left leg two-hour post-envenomation and subsequently received four vials of Crotalidae polyvalent immune fab (ovine). At three-hour post-envenomation following transfer to the intensive care unit, an electrocardiogram revealed new-onset atrial fibrillation. An amiodarone drip was started and the patient successfully converted to normal sinus rhythm approximately six hours after he was found to be in atrial fibrillation. A transthoracic echocardiogram revealed mild concentric left ventricular hypertrophy and an ejection fraction of 72%. He was discharged the following day with no hematological abnormalities and a baseline first-degree atrioventricular block. Conclusion This is the first documented case of reversible atrial fibrillation precipitated by Crotalinae envenomation. In patients with pertinent risk factors for developing atrial fibrillation, physicians should be aware of the potential for this arrhythmia. Direct toxic effects of venom or structural and electrophysiological cardiovascular abnormalities may predispose snakebite patients to arrhythmia, warranting extended and attentive cardiac monitoring.(AU)

Amiodarone may prevent the tilmicosin-caused lethal toxicity

Background: Tilmicosin is widely used in veterinary medicine and its accidental overdose by injection may cause death viacausing negative inotropy and positive chronotropy in both the treated animal and the veterinarian. In addition, there is noany antidote against to tilmicosin-caused death. Amiodarone blocks some channels in the heart, but it has much complexeffect including vagotonic, bradycardic etc on the heart. Considering vagotonic and bradycardic effects of amiodarone, ithas been hypothesised that amiodarone may prevent tilmicosin-caused death. The aim of this study was to determine theeffect of amiodarone on the survival rate of rats in tilmicosin-caused lethal toxicity.Materials, Methods & Results: Twenty female Wistar rats (body weight: 288 ± 33.8 g, age: 7-8 months) were used in thisstudy. The study protocol was approved by the Ethical Committee. Rats received food and water ad libitum. The rats weredivided into two groups containing 10 rats each. Rats in Group 1 were administered 360 mg/kg of tilmicosin in a singlesubcutaneous injection. Rats in Group 2 were administered 25 mg/kg of amiodarone via the tail vein at 8. min after thesingle subcutaneous injection of tilmicosin in a dose of 360 mg/kg. After the injections, deaths were recorded at 0, 2, 6, 10,12 and 24 h. At the end of the 24-h period, survival/death ratio was analysed by the Chi-square test. The level of statisticalsignifi cance was set at P < 0.05. The survival rate of Group 2 (40%) was statistically signifi cantly (P < 0.025) higher thanthat of Group 1 (0.0%). In control group all rats died at 10 h after subcutaneously tilmicosin injection. In Group 2 wereadministered 25 mg/kg of amiodarone (intravenously) at 8 min after the single subcutaneous injection of tilmicosin in adose of 360 mg/kg, and 2 rats died at 2 h and 4...(AU)

Amiodarone may prevent the tilmicosin-caused lethal toxicity

Background: Tilmicosin is widely used in veterinary medicine and its accidental overdose by injection may cause death viacausing negative inotropy and positive chronotropy in both the treated animal and the veterinarian. In addition, there is noany antidote against to tilmicosin-caused death. Amiodarone blocks some channels in the heart, but it has much complexeffect including vagotonic, bradycardic etc on the heart. Considering vagotonic and bradycardic effects of amiodarone, ithas been hypothesised that amiodarone may prevent tilmicosin-caused death. The aim of this study was to determine theeffect of amiodarone on the survival rate of rats in tilmicosin-caused lethal toxicity.Materials, Methods & Results: Twenty female Wistar rats (body weight: 288 ± 33.8 g, age: 7-8 months) were used in thisstudy. The study protocol was approved by the Ethical Committee. Rats received food and water ad libitum. The rats weredivided into two groups containing 10 rats each. Rats in Group 1 were administered 360 mg/kg of tilmicosin in a singlesubcutaneous injection. Rats in Group 2 were administered 25 mg/kg of amiodarone via the tail vein at 8. min after thesingle subcutaneous injection of tilmicosin in a dose of 360 mg/kg. After the injections, deaths were recorded at 0, 2, 6, 10,12 and 24 h. At the end of the 24-h period, survival/death ratio was analysed by the Chi-square test. The level of statisticalsignifi cance was set at P < 0.05. The survival rate of Group 2 (40%) was statistically signifi cantly (P < 0.025) higher thanthat of Group 1 (0.0%). In control group all rats died at 10 h after subcutaneously tilmicosin injection. In Group 2 wereadministered 25 mg/kg of amiodarone (intravenously) at 8 min after the single subcutaneous injection of tilmicosin in adose of 360 mg/kg, and 2 rats died at 2 h and 4...

Hemodynamic and antiarrhythmic effects of lidocaine or amiodarone in dogs anesthetized with halothane / Efeitos hemodinâmicos e antiarrítmicos da lidocaína ou amiodarona em cães anestesiados com halotano

The effects of continuous rate infusion of lidocaine or amiodarone on hemodynamic and arrhythmias induced by epinephrine in dogs anesthetized with halothane were evaluated. Thirty dogs were distributed into three groups: amiodarone group (AG), lidocaine group (LG), or control group (CG). Anesthesia was induced with etomidate and maintained with halothane. Thirty minutes later a bolus and continuous rate infusion (CRI) of amiodarone in AG, lidocaine in LG and NaCl at 0.9% in CG was administered. After 10 minutes, arrhythmias were induced by epinephrine CRI at 0.0001mg/kg/minute, which was increased in 0.0001mg/kg/minute every ten minutes, until 0.0003mg/kg/minute. The measurements were performed 30 minutes after the induction of anesthesia (T0), 10 minutes after beginning the drug CRIs (T1), 10 minutes after beginning epinephrine administration (T2) and 10 minutes after increasing epinephrine CRI (T3 and T4). In CG, at T3 heart rate (HR) was greater than in LG, while at T4, HR in GC was higher than in LG and AG. In LG and CG, from T2, central venous pressure (CVP), cardiac index (CI), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), mean pulmonary arterial pressure (mPAP) increased. In AG, SAP, DAP and MAP it decreased from T1 to T3. The ventricular ectopic beats (VEB) were lower in AG. Amiodarone has better antiarrhythmogenic effects, although it was also associated with hypotension.(AU)

Avaliaram-se os efeitos da infusão contínua de lidocaína ou amiodarona sobre a hemodinâmica e as arritmias induzidas pela epinefrina em cães anestesiados com halotano. Trinta animais foram distribuídos em três grupos: grupo amiodarona (GA), grupo lidocaína (GL) ou grupo-controle (GC). A anestesia foi induzida com etomidato e mantida com halotano. Trinta minutos após, foram administrados bolus e infusão contínua (CRI) de amiodarona no GA, de lidocaína no GL e de NaCl a 0,9% no GC. Após 10 minutos, iniciou-se a CRI de epinefrina (0,0001mg/kg/minuto), aumentando-se 0,0001mg/kg/minuto a cada 10 minutos até 0,0003mg/kg/minuto. As mensurações foram realizadas 30 minutos após a indução anestésica (T0), 10 minutos após a CRI dos fármacos (T1), 10 minutos após a administração de epinefrina (T2) e a cada 10 minutos após o incremento na CRI de epinefrina (T3 e T4). A frequência cardíaca (FC) foi maior no GC que no GL em T3 e maior em GC que nos demais grupos em T4. A partir de T2, houve aumento na pressão venosa central (PVC), no índice cardíaco (IC), nas pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) e na pressão média da artéria pulmonar (PAPm) no GL e no GC. No GA, PAS, PAD e PAM diminuíram de T1 a T3. Os batimentos ventriculares ectópicos (BVE) foram menores no GA. Amiodarona possui melhores efeitos antiarrítmicos, apesar de também estar associada com hipotensão.(AU)