Background Haloperidol is the most frequently prescribed antipsycbotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been inv...Background Haloperidol is the most frequently prescribed antipsycbotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been investigated in a randomised placebo-controlled fixed-dose study. Methods A subanalysis of a randomised double-blind placebo-controlled study was conducted to evaluate the effect of prophylactic haloperidol 1 mg or placebo 1 mg orally twice-daily （maximum of 14 doses） on QTc interval in patients aged 70 years and over. Bedside, 12-lead ECGs were recorded before, during and after the one-week intervention period. Automatic QTc measurements were ob- tained in addition to manual measurements of QT and RR intervals, blinded for treatment status. Manual measurements were corrected （QTc） using Bazett （QTc-B）, Framingham （QTc-Fa）, Fridericia （QTc-Fi） and Hodges （QTc-H） methods. Mixed model analyses were used to test for differences in longitudinal course of QTc between patients receiving haloperidol and placebo. Results ECG recordings of 72 patients （haloperidol n = 38） were analysed, 45.8% male. Median （range） haloperidol serum concentration on day 4 was 0.71 （0.32-1.82） μg/L （n = 23）. Longitudinal course of mean QTc did not significantly differ between treatment arms for any of the automatic or manually derived QTc values. Conclusions Low dose oral haloperidol did not result in QTc prolongation in older acutely hospitalised patients. Results may not be generalizable to patients with existing ECG abnormalities such as atrial fibrillation.展开更多
BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safet...BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safety of psychotropic medications in the reproductive age female has not been well established.This review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during pregnancy.METHODS:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant female.RESULTS:While nonpharmacological management is preferred,ED visits for agitation often require medical management.Medication should be selected based on the etiology of agitation and the clinical setting to avoid major adverse effects.Adverse effects are common in pregnant females.For mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse effects.In moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on hemodynamics.Haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy.Second generation psychotropics are often utilized as second-line therapy,including risperidone.Benzodiazepines and ketamine have demonstrated adverse fetal outcomes.CONCLUSION:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in utero.As the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.展开更多
Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a sp...Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase. Methods Brain ventricular and intraperitoneal injections were used for haloperidol administration, Western blots for tau phosphorylation, 32P-labeling for PKA and GSK-3 activity, and high performance liquid chromatograph for detection of serum melatonin levels. Results Haloperidol injection through the lateral ventricle and intraperitoneal reinforcement significantly stimulated PKA activity with a concurrent hyperphosphorylation of tau at M4 (Thr231/Ser235) and PS214 (Ser214) sites. Prior treatment of the rats using melatonin supplement for one week and reinforcement during the haloperidol administration arrested PKA activity and attenuated tau hyperphosphorylation. GSK-3 activity showed no obvious change after haloperidol injection, however, melatonin supplements and reinforcements during haloperidol infusion inactivated basal activity of GSK-3. Conclusion Decreased melatonin may be involved in Alzheimer-like tau hyperphosphorylation, and overactivation of PKA may play a crucial role in this process.展开更多
文摘Background Haloperidol is the most frequently prescribed antipsycbotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been investigated in a randomised placebo-controlled fixed-dose study. Methods A subanalysis of a randomised double-blind placebo-controlled study was conducted to evaluate the effect of prophylactic haloperidol 1 mg or placebo 1 mg orally twice-daily （maximum of 14 doses） on QTc interval in patients aged 70 years and over. Bedside, 12-lead ECGs were recorded before, during and after the one-week intervention period. Automatic QTc measurements were ob- tained in addition to manual measurements of QT and RR intervals, blinded for treatment status. Manual measurements were corrected （QTc） using Bazett （QTc-B）, Framingham （QTc-Fa）, Fridericia （QTc-Fi） and Hodges （QTc-H） methods. Mixed model analyses were used to test for differences in longitudinal course of QTc between patients receiving haloperidol and placebo. Results ECG recordings of 72 patients （haloperidol n = 38） were analysed, 45.8% male. Median （range） haloperidol serum concentration on day 4 was 0.71 （0.32-1.82） μg/L （n = 23）. Longitudinal course of mean QTc did not significantly differ between treatment arms for any of the automatic or manually derived QTc values. Conclusions Low dose oral haloperidol did not result in QTc prolongation in older acutely hospitalised patients. Results may not be generalizable to patients with existing ECG abnormalities such as atrial fibrillation.
文摘BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safety of psychotropic medications in the reproductive age female has not been well established.This review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during pregnancy.METHODS:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant female.RESULTS:While nonpharmacological management is preferred,ED visits for agitation often require medical management.Medication should be selected based on the etiology of agitation and the clinical setting to avoid major adverse effects.Adverse effects are common in pregnant females.For mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse effects.In moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on hemodynamics.Haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy.Second generation psychotropics are often utilized as second-line therapy,including risperidone.Benzodiazepines and ketamine have demonstrated adverse fetal outcomes.CONCLUSION:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in utero.As the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.
基金Supported by grands from theNaturalScience Foundation of China(39925012 and 30170221 ),and the Scienceand Technology Committee of China (G1999054007).
文摘Objective To investigate effect of inhibiting melatonin biosynthesis on activities of protein kinase A (PKA), glycogen synthase kinase-3 (GSK-3) and tau phosphorylation at PS214 and M4 epitopes using haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase. Methods Brain ventricular and intraperitoneal injections were used for haloperidol administration, Western blots for tau phosphorylation, 32P-labeling for PKA and GSK-3 activity, and high performance liquid chromatograph for detection of serum melatonin levels. Results Haloperidol injection through the lateral ventricle and intraperitoneal reinforcement significantly stimulated PKA activity with a concurrent hyperphosphorylation of tau at M4 (Thr231/Ser235) and PS214 (Ser214) sites. Prior treatment of the rats using melatonin supplement for one week and reinforcement during the haloperidol administration arrested PKA activity and attenuated tau hyperphosphorylation. GSK-3 activity showed no obvious change after haloperidol injection, however, melatonin supplements and reinforcements during haloperidol infusion inactivated basal activity of GSK-3. Conclusion Decreased melatonin may be involved in Alzheimer-like tau hyperphosphorylation, and overactivation of PKA may play a crucial role in this process.
