Continuation of Proton Pump Inhibitors from Hospital to Community

Objectives To evaluate the appropriateness of initiation of proton pump inhibitor (PPI) treatment in hospital, the quality of discharge information, and any association with continued treatment in the community.Method Survey of all inpatients newly initiated on a PPI in June–August 2003. Assessment of appropriateness of therapy and completeness of discharge information; assessment of continuation of PPI therapy in the community after 6 months.Results Thirty-five of 58 patients (60%) were considered appropriately commenced on PPI treatment. Less than 25% of patients discharged on a PPI had discharge information recommending duration of treatment or review. In the “appropriate” group 30 patients (86%) were discharged on omeprazole, and 13/21 (62%) evaluable patients remained on this at 6 months. In the “inappropriate” group 15 (65%) were discharged on omeprazole, and 10/14 (71%) evaluable patients remained on this at 6 months. Older patients remained on omeprazole for a longer duration but appropriateness of commencement did not influence the duration of treatment. Dose titration was attempted for 10 (29%) patients including three from the “inappropriate” group.Conclusion Care should be taken to commence PPIs only when clinically indicated. Discharge information to GPs, especially recommendations for duration of treatment and/or dose titration, requires improvement.     

Pharmacokinetics and Pharmacodynamics of the Antiplatelet Combination Aspirin (Acetylsalicylic Acid) Plus Extended-Release Dipyridamole Are Not Altered by Coadministration with the Potent CYP2C19 Inhibitor Omeprazole

Background

The fixed-dose combination of aspirin (acetylsalicylic acid) 25 mg plus extended-release dipyridamole 200 mg (ASA + ER-DP) is used for long-term secondary stroke prevention in patients who have experienced non-cardioembolic stroke or transient ischemic attack. Although the theoretical risk is low that the antiplatelet activity of ASA + ER-DP will be affected by concomitant use of a proton pump inhibitor (PPI), no formal drug-drug interaction studies have been conducted.

Objective

This study aimed to determine whether the PPI omeprazole influences the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of ASA + ER-DP.

Study Design and Setting

This was a randomized, open-label, multiple-dose, crossover, drug-drug interaction study carried out in a clinical trial unit.

Participants

Sixty healthy male and female volunteers aged 18–50 years were included in the study.

Intervention

Participants were randomized to one of two treatment sequences (ABCD or CDAB), each comprising four 7-day treatments with a washout of ≥14 days between the second and third treatments. Treatment A = ASA + ER-DP 25 mg/200 mg (Aggrenox^®) twice daily (BID) alone; B = ASA + ER-DP 25 mg/200 mg BID + omeprazole (Prilosec^®) 80 mg once daily (QD) following ASA + ER-DP alone for 7 days; C = omeprazole 80 mg QD alone; D = omeprazole 80 mg QD + ASA + ER-DP 25 mg/200 mg BID following omeprazole alone for 7 days.

Main Outcome Measures

The main outcome measures were systemic PK exposure to ER-DP and ASA inhibition of arachidonic acid-induced platelet aggregation.

Results

Systemic exposure to ER-DP was similar with and without omeprazole, based on steady-state area under the concentration-time curve (AUC) from 0 to 12 h (AUC_0–12,ss, ng·h/mL) and maximum plasma concentration (C_max,ss, ng/mL). For the treatment comparison D versus A, the percent mean ratios were 96.38 (90 % confidence interval [CI] 90.96–102.13) for AUC_0–12,ss and 92.03 (86.95–97.40) for C_max,ss. The ER-DP concentration versus time profiles were nearly superimposable. There was no effect on the PDs of the ASA component: the extent of ASA inhibition of arachidonic acid-induced platelet aggregation was almost identical with and without omeprazole, with a percent mean ratio for treatment D versus A = 99.02 (90 % CI 98.32–99.72) at 4 h after last dose. All treatments were well tolerated.

Conclusion

The PK and PD behavior of ASA + ER-DP was not altered by concurrent administration of omeprazole.     

Coronary computerized tomography angiography for rapid discharge of low-risk patients with cocaine-associated chest pain

Background

Most patients presenting to emergency departments (EDs) with cocaine-associated chest pain are admitted for at least 12 hours and receive a “rule out acute coronary syndrome” protocol, often with noninvasive testing prior to discharge. In patients without cocaine use, coronary computerized tomography angiography (CTA) has been shown to be useful for identifying a group of patients at low risk for cardiac events who can be safely discharged. It is unclear whether a coronary CTA strategy would be efficacious in cocaine-associated chest pain, as coronary vasospasm may account for some of the ischemia. We studied whether a negative coronary CTA in patients with cocaine-associated chest pain could identify a subset safe for discharge.

Methods

We prospectively evaluated the safety of coronary CTA for low-risk patients who presented to the ED with cocaineassociated chest pain (self-reported or positive urine test). Consecutive patients received either immediate coronary CTA in the ED (without serial markers) or underwent coronary CTA after a brief observation period with serial cardiac marker measurements. Patients with negative coronary CTA (maximal stenosis less than 50%) were discharged. The main outcome was 30-day cardiovascular death or myocardial infarction.

Results

A total of 59 patients with cocaine-associated chest pain were evaluated. Patients had a mean age of 45.6 ± 6.6 yrs and were 86% black, 66% male. Seventy-nine percent had a normal or nonspecific ECG and 85% had a TIMI score < 2. Twenty patients received coronary CTA immediately in the ED, 18 of whom were discharged following CTA (90%). Thirty-nine received coronary CTA after a brief observation period, with 37 discharged home following CTA (95%). Six patients had coronary stenosis ≥50%. During the 30-day follow-up period, no patients died of a cardiovascular event (0%; 95% CI, 0–6.1%) and no patient sustained a nonfatal myocardial infarction (0%; 95% CI, 0–6.1%).

Conclusions

Although cocaine-associated myocardial ischemia can result from coronary vasoconstriction, patients with cocaineassociated chest pain, a non-ischemic ECG, and a TIMI risk score < 2 may be safely discharged from the ED after a negative coronary CTA with a low risk of 30-day adverse events.     

Pilot study to assess the influence of an enhanced medication plan on patient knowledge at hospital discharge

Purpose

This study assessed the effect of providing an enhanced medication plan (EMP) to patients during patient-physician conversation at hospital discharge and evaluated its immediate impact on patient knowledge on pharmacotherapy.

Methods

We observed patient-physician conversations at hospital discharge in three internal medicine wards of the University Hospital Heidelberg before and after the EMP was integrated into the discharge process, and documented how and to what extent physicians provided the patients with drug information. After the conversation, the patients’ knowledge was evaluated by three standardized questions about their pharmacotherapy.

Results

We observed 90 conversations (50 before EMP-implementation, 40 after). In both phases, the conversation duration was 5.6–6 min (p?=?0.56). However, the time spent on drug information increased significantly by 61.7 % after EMP-implementation (+63 s, p?=?0.02). Before implementation, physicians gave at least one drug administration recommendation for 75.1 % of all drugs, compared to 84.6 % after implementation (p?=?0.02). The EMP provided information for almost all drugs (98.9 %; p?p?Conclusion The provision of an EMP improves information transfer and therefore increases the patients’ knowledge of their individual drug treatment without prolonging the overall discharge process.     

Comparison of acid inhibition with standard dosages of proton pump inhibitors in relation to CYP2C19 genotype in Japanese

Introduction

The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power.

Methods

Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers.

Results

Median pH with rabeprazole was 5.4 (3.3–7.5), which was significantly greater than with either omeprazole [4.4 (2.1–7.3)] or lansoprazole [4.8 (3.5–6.4)] (both P?Discussion Treatment with the selected PPIs at their standard dosages had difficulty maintaining acid inhibition for a full 24 h, especially in CYP2C19 EM. However, rabeprazole has the merit of less influence of CYP2C19 genotype compared with the other PPIs.     

Tenofovir-induced nephrotoxicity: incidence,mechanism, risk factors,prognosis and proposed agents for prevention

Objective

In this study, data regarding epidemiology, risk factors, pathogenesis and outcome of tenofovir-induced nephrotoxicity will be reviewed, and current and future approaches for prevention will be discussed.

Method

The data were collected by searching Scopus, PubMed, Medline, Science direct, Clinical trials and Cochrane database systematic reviews. The keywords used as search terms were “Tenofovir”, “TDF”, “NRTI”, “Nephrotoxicity”, “Renal failure”, “Kidney damage”, “HIV” and “AIDS”.

Results and conclusion

Several predisposing factors including elevated baseline SCr, concomitant nephrotoxic medications, low body weight, advanced age, tenofovir disoproxil fumarate (TDF) dose and duration of treatment and lower CD4 cell count were identified as risk factors for development of TDF-induced nephrotoxicity. Cellular accumulation through increased entry from the human organic anion transporters and decreased efflux into tubular lumen is main mechanism of nucleotide analogue antiviral induced nephrotoxicity. Renal function assessment and monitoring at baseline and during TDF treatment are the main approach of prevention of TDF-induced nephrotoxicity. Rosiglitazone may be helpful in patients presenting with TDF-induced nephrotoxicity. Pretreatment with melatonin prevented all known histological changes in proximal tubular mitochondira induced by TDF. Use of antioxidants with mitochondria-targeted properties such as MitoQ or Mito-CP may prevent proximal tubular mitochondrial against TDF damage. Vitamin E, ebselen, lipoic acid, plastoquinone, nitroxides, SOD enzyme mimetics, Szeto-Schiller (SS) peptides, and quercetin are other potential agents for prevention of TDF-induced nephrotoxicity. However, data regarding effectiveness of nephroprotective agents against TDF-induced nephrotoxicity are not conclusive. Before extrapolation of the preclinical evidence to clinical practice, these evidence should be confirmed in future human studies.     

Critical role of nitric oxide in the modulation of prepulse inhibition in Swiss mice

Rationale

Nitric oxide (NO) modulates the dopamine uptake and release processes and appears to be implicated in dopamine-related pathologies, such as schizophrenia. However, it is unclear whether there is excess or deficient NO synthesis in schizophrenia pathophysiology. Analyses of the intracellular pathways downstream of NO system activation have identified the cyclic nucleotide cyclic guanosine monophosphate (cGMP) as a possible target for drug development. Defects in the sensorimotor gating of the neural mechanism underlying the integration and processing of sensory information have been detected across species through prepulse inhibition (PPI).

Objectives

The aim of this study was to investigate the effects of NO/cGMP increase on sensorimotor gating modulation during dopamine hyperfunction.

Methods

Mice were treated with NO donors and subjected to the PPI test. Treatment with the NO donor sodium nitroprusside was preceded by pretreatment with a soluble guanylate cyclase (sGC) inhibitor. Additionally, the mice were treated with NO donors and phosphodiesterases inhibitors prior to amphetamine treatment.

Results

Pretreatment with the NO donors enhanced the PPI response and attenuated the amphetamine-disruptive effects on the PPI. The sGC inhibitor did not modify the sodium nitroprusside effects. Additionally, the cGMP increase induced by a specific phosphodiesterase inhibitor did not modify the amphetamine-disruptive effect.

Conclusions

This study provides the first demonstration that an increase in NO can improve the PPI response and block the amphetamine-disruptive effects on the PPI response. Our data are consistent with recent clinical results. However, these effects do not appear to be related to an increase in cGMP levels, and further investigation is thus required.     

Effectiveness of oral bisphosphonates for primary prevention of osteoporotic fractures

Purpose

Osteoporosis is a chronic disease of the bone, whose incidence increases progressively with aging. The main consequences of osteoporosis are fragility fractures, which have considerable medical, social, and economic implications. Adequate treatment of osteoporosis must be considered as a compelling public health intervention. Bisphosphonates (BPs) represent the most significant advance in this field in the past decade, and they are widely used in the treatment of osteoporosis. However, evidence for their effectiveness is limited to secondary prevention, whereas their effect in primary prevention is uncertain and needs further investigation.

Methods

Using administrative data collected in the “Biphosphonates Efficacy-Safety Tradeoff” (BEST) study, a nested case-control study was conducted by including 56,058 participants, aged 55 years who were started on oral BPs from 2003 to 2005. Cases were the 1,710 participants who were hospitalized for osteoporotic fractures until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio of fracture associated with categories of treatment duration.

Results

Compared with participants assuming BPs for less than 1 year, those who remained on therapy for at least 2 years had a 21 % (95 % confidence interval (CI) 7 to 33 %) fracture risk reduction.

Conclusion

This study provides evidence that BPs, dispensed for primary prevention of osteoporotic fractures, are associated with a reduced risk of osteoporotic fractures after at least 2 years of treatment.     

Effects of dopamine D2 agonist quinpirole on neuronal activity of anterior cingulate cortex and striatum in rats

Rationale

The influence of acute D2 agonist quinpirole on locomotor activity has been effectively characterized. However, few studies have addressed the dynamic changes in neuronal activity of the anterior cingulate cortex (ACC) and striatum (STR), two crucial regions for cognitive and motor functions, after quinpirole administration.

Objective

This study was conducted in order to acquire detailed information on the evoked activity of the neurons in the ACC and STR after acute quinpirole administration.

Methods

Multichannel electrophysiological recording was used for tracking neuronal activity in the ACC and STR of urethane-anesthetized rats after administration of saline or 0.05 or 0.5 mg/kg quinpirole.

Results

In contrast to the responses to saline, quinpirole dose-dependently increased the ratio of neurons, the activity of which was inhibited in the ACC and STR. By examining the ensemble neuronal activities of inhibition-responded neurons, there was no significant activity difference among the “treatments” (saline and low- and high-dose quinpirole), the “periods” (the duration of 0–15 and 16–45 min after i.v. injection), and the interaction between “treatments” and “periods.” Regarding activation-responded neurons, however, there was a significant “periods” difference in both ACC and STR, and the activity of 16–45 min was significantly higher than the activity of 0–15 min after high-dose quinpirole administration in ACC (p?<?0.05) and STR (p?<?0.001).

Conclusion

Dose-dependent ACC and STR neuronal responses to quinpirole may offer a possible mechanism for understanding the locomotor responses to quinpirole in behaving rats. The late excitatory effect of high-dose quinpirole in the STR further suggests that this region would be critical for the activation of locomotor activity.     

Pharmacoeconomic comparison of Helicobacter pylori eradication regimens

Background

Helicobacter pylori is the most important etiologic agent for development of peptic ulcer, chronic gastritis and gastric carcinomas. It is now well established that H. pylori eradication treatment is more cost-effective than acid suppressing therapies alone for the treatment of peptic ulcer disease. However, the comparative cost-effectiveness of various H. pylori eradication regimens is still not clear.

Objective

This study was designed to make a pharmacoeconomic comparison of different H. pylori eradication regimens in patients with peptic ulcer disease or chronic gastritis, using real-world cost and effectiveness data.

Setting

Istanbul University Hospital and Marmara University Hospital.

Method

A total of 75 patients diagnosed as H. pylori (+) by endoscopy were randomized to receive one of the seven H. pylori treatment protocols. These protocols were as follows: (LAC) = ‘lansoprazole 30 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid’ for 7 days and (OCM) = ‘omeprazole 20 mg bid + clarithromycin 250 mg bid + metronidazole 500 mg bid’; (OAM) = ‘omeprazole 40 mg qd + amoxicillin 500 mg tid + metronidazole 500 mg tid’; (MARB) = ‘metronidazole 250 mg tid + amoxicillin 500 mg qid + ranitidine 300 mg hs + bismuth 300 mg qid’; (OAC) = omeprazole 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid’; (OCA) = omeprazole 40 mg bid + clarithromycin 500 mg bid + amoxicillin 1 g bid’; (OAB) = ‘omeprazole 20 mg bid + amoxicillin 500 mg tid + bismuth 300 mg qid’ each for 14 days. Only direct costs were included in the analysis. Effectiveness was measured in terms of “successful eradication”. The cost-effectiveness ratios of the regimens were calculated using these effectiveness and cost data. The perspective of the study was assumed as the Government’s perspective.

Main outcome measure

Cost-effectiveness ratios of eradication regimens.

Results

MARB and OCA regimens were found to be more cost-effective than the other treatment regimens. The eradication rates and cost-effectiveness ratios calculated for these protocols were 90% (€158.7) for MARB and 90% (€195.8) for OCA regimen.

Conclusion

This study confirms the importance of using local pharmacoeconomic data. Analyses such as this give decision-makers the tools to choose a better treatment option which is both highly effective yet and has a low cost.     

MitoPark mice,an animal model of Parkinson’s disease,show enhanced prepulse inhibition of acoustic startle and no loss of gating in response to the adenosine A2A antagonist SCH 412348

Rationale

Psychoses are debilitating side effects associated with current dopaminergic treatments for Parkinson's disease (PD). Prepulse inhibition (PPI), in which a non-startling stimulus reduces startle response to a subsequent startle-eliciting stimulus, is important in filtering out extraneous sensory stimuli. PPI deficits induced by dopamine agonists can model symptoms of psychosis. Adenosine A_2A receptor antagonists, being developed as novel PD treatments, indirectly modulate dopamine signaling in the basal ganglia and may have an improved psychosis profile which could be detected using the PPI model.

Objectives

The aims of this study is to characterize PPI in MitoPark mice, which exhibit progressive loss of dopamine signaling and develop a Parkinson-like motor phenotype, and assess standard and novel PD treatment effects on PPI in MitoPark mice, which more closely mimic the basal ganglia dopamine status of PD patients.

Results

MitoPark mice displayed enhanced PPI as dopamine tone decreased with age, consistent with studies in intact mice that show enhanced PPI in response to dopamine antagonists. Paradoxically, older MitoParks were more sensitive to PPI disruption when challenged with dopamine agonists such as apomorphine or pramipexole. Alternatively, SCH 412348, an adenosine A_2A antagonist, did not disrupt PPI in MitoPark mice at doses that normalized hypoactivity.

Conclusion

Use of MitoPark mice in the PPI assay to assess the potential for PD treatment to produce psychoses likely represents a more disease-relevant model. SCH 412348 does not differentially disrupt PPI as do dopamine agonists, perhaps indicative of an improved psychosis profile of adenosine A_2A antagonists, even in PD patients with decreased dopamine tone in the basal ganglia.     

A systematic review of reported cases involving psychotic symptoms worsened by aripiprazole in schizophrenia or schizoaffective disorder

Rationale

Numerous case reports have suggested that aripiprazole can worsen psychotic symptoms in schizophrenia.

Objectives

We reviewed reported cases which have suggested that aripiprazole can worsen psychotic symptoms in schizophrenia and evaluated each regarding quality of the causal relationship.

Methods

A systematic literature search was conducted on August 18, 2012, using the PubMed and the EMBASE. Twenty-two cases met the following inclusion criteria: (1) diagnosis of schizophrenia or schizoaffective disorder, (2) worsening of psychotic symptoms associated with aripiprazole, and (3) aripiprazole dose ≤30 mg/day. Information about the causal relationship between aripiprazole and increased psychotic symptoms was extracted. The quality of the causal relationship was evaluated according to the modified guidelines for evaluation of drug-associated events and classified as “questionable,” “moderately suggestive,” or “highly suggestive.”

Results

Patients were chronic in at least 15 cases, and prior antipsychotic dose exceeded recommended guidelines in 19 cases. Psychotic symptoms worsened after simply adding aripiprazole to the current regimen in eight cases. Besides psychotic symptoms, increasing agitation (nine cases), aggression (11 cases), and/or activation (seven cases) were reported. Clinical resolution occurred after aripiprazole discontinuation in eight cases. Regarding causal relationship, 11 cases were classified as “highly suggestive,” three as “moderately suggestive,” and eight as “questionable”.

Conclusions

Clinicians should be vigilant when adding aripiprazole to patients with chronic schizophrenia also receiving relatively high doses of other antipsychotics, and discontinuation of aripiprazole should be considered if psychotic symptoms and/or agitation/aggression/activation increase.     

Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review

Purpose

Treatment failures following vancomycin therapy in patients with methicillin-resistant Staphylococcus aureus infections have led to the utilization of higher doses of this antibiotic to achieve the trough concentrations of 10–20?μg/mL recommended by the Infectious Diseases Society of America clinical practice guideline. However, many questions remain on the safety of such high doses of vancomycin, specifically their nephrotoxic effects. In this review, we have collected available evidence on the nephrotoxicity of vancomycin, particularly in terms of its mechanism, incidence, predisposing factors and special target populations.

Method

The data were collected by searching Scopus, PubMed, Medline, and Cochrane database systematic reviews. The key words used as search terms were “vancomycin”, “nephrotoxicity”, “renal failure”, “renal damage”, “risk factors”, “infants”, “children”, “adult”, “elderly” and “pregnancy”. We have included all relevant animal and human studies up to the date of publication.

Results and conclusion

Vancomycin-induced renal toxicity was reported in 10–20 % and 30–40 % of patients following conventional and high doses of vancomycin therapy, respectively .The most probable mechanism for its nephrotoxicity can be at least partially attributable to an increased production of reactive oxygen species and oxidative stress. There are a number of different risk factors which could accelerate or potentiate the occurrence of vancomycin-induced nephrotoxicity, with the most documented risk factors being high trough vancomycin level (especially >20?mg/L) or doses (>4?g/day), concomitant treatment with nephrotoxic agents, prolonged therapy (even more than 7?days), and admittance to an intensive care unit (especially prolonged stay). It is necessary to carry out more studies, especially those focused on the association between nephrotoxicity and high trough levels of vancomycin.     

A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans

Rationale/objectives

This study examined the effects of propranolol vs. placebo, administered immediately after a “retrieval” session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent “test” session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up.

Methods

CD participants received either 40 mg propranolol or placebo immediately following a “retrieval” CCE session. The next day, participants received a “test” session of CCE that was identical to the “retrieval” session except no medication was administered. Participants underwent a “follow-up” CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions.

Results

Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use.

Conclusions

This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted.     

Zigadenus poisoning treated with atropine and dopamine

Introduction

Zigadenus (commonly known as “death camas” or “mountain camas”) is a common plant in the lilly family found throughout the United States. Its onion-like roots can be mistaken for an edible plant. Ingestion may cause hemodynamic instability which has successfully been treated with atropine. It has been suggested that vasopressors may be an effective therapy for this ingestion. We report the successful use of dopamine as therapy inZigadenus ingestion.

Case Report

A 45 year-old, previously healthy male presented to the ED with complaints of severe nausea and vomiting after ingesting two “wild onion” bulbs. He was noted to have marked hypotension and bradycardia in the ED, which initially responded to treatment with IV fluids and atropine. The plant was identified as a species ofZigadenus. After a second drop in heart rate and blood pressure in the ICU, hypotension and bradycardia were treated successfully with a dopamine infusion.

Discussion

Zigadenus ingestion presents with vomiting, hypotension and bradycardia. The hemodynamic instability responded well to atropine for 1–2 hours. Dopamine infusion was used to stabilize both heart rate and blood pressure. With supportive care, poisoned individuals become relatively asymptomatic within 24 hours of their ingestion. Patients may be discharged once asymptomatic, typically the day after ingestion, and do not have any known long term sequelae.

Conclusion

Zigadenus poisoning causes vomiting, hypotension and bradycardia. The hemodynamic instability may be treated with atropine administration and dopamine infusion.     

The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism

Rationale

Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence.

Objectives

We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI.

Methods

We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured.

Results

Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation.

Conclusions

The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.     

Dopamine on D2-like receptors “reboosts” dopamine D1-like receptor-mediated behavioural activation in rats licking for a isotonic NaCl solution

Rationale

We recently suggested that dopamine on D1-like receptors is involved in the activation of goal-directed responses and the level of response activation is “reboosted” on the basis of an evaluation process involving D2-like receptors assessing “response efficacy”. A main piece of evidence in support of this hypothesis was the observation of an “extinction mimicry” effect in the time course of licking bursts after dopamine D2-like receptor blockade in rats licking for sucrose.

Objectives

The aim of this study was to determine whether the pattern of licking observed with sucrose as a reward could be reproduced in rats licking for a different reward (0.9 % NaCl).

Materials and methods

We investigated the effects of the dopamine D1-like receptor antagonist SCH 23390 (0.01–0.04 mg/kg) and of the dopamine D2-like receptor antagonist raclopride (0.025–0.25 mg/kg) on the microstructure of licking for a 0.9 % NaCl solution in 12-h water-deprived rats in 30-min sessions.

Results

As previously observed with sucrose as a reward, raclopride reduced the size of licking bursts and produced on the burst number time course an “extinction mimicry” effect, while SCH 23390 reduced licking exclusively by reducing burst number.

Conclusions

These results are consistent with the proposed hypothesis and provide support to the use of the study of licking microstructure as a valid model not only for the investigation of the mechanisms governing ingestive behaviour but also for the investigation of the mechanisms underlying behavioural activation and the related evaluation processes.