尖端扭转型室性心动过速治疗体会

目的 观察硫酸镁与电复律终止尖端扭转型室性心动过速(Tdp VT)患者的疗效及安全性.方法 回顾分析硫酸镁与电复律终止Tdp VT患者21例次的临床资料.结果 TdpVT发作时应用硫酸镁终止者5例次,成功3例,成功率60.00%;电复律16例次,成功15例次,成功率93.75%.结论 硫酸镁与电复律终止TdpVT发作均安全有效,电复律成功率更高.     

Citalopram,a selective serotonin reuptake inhibitor: Clinical antidepressive and long-term effect — a phase II study

In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three nonendogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remaining 19 patients completed a 4–6 week treatment schedule. Of 16 endogenously depressed patients 11 responded, one was a partial responder and four did not respond. Of three patients with non-endogenous depressions, two responded and one did not respond.No correlation between plasma citalopram concentration and therapeutic outcome was found.Fourteen patients were given maintenance treatment for 8–113 weeks. One patient developed depression when the dose was reduced from 60 to 40 mg and one patient became manic. After discontinuation of treatment seven patients had a depressive relapse and six of these who again were treated with citalopram responded completely.Side effect rating scores of symptoms usually associated with depression or treatment with tricyclic antidepressants declined during treatment. Three patients complained of increased need of sleep for a period after several weeks of treatment. Apart from an unspecific, transient rise in liver enzymes in two patients, detailed biochemical laboratory tests were all normal. There were no effects on blood pressure, pulse rate, orthostatic reaction, or electrocardiogram. One patient took an overdose of citalopram resulting in plasma levels about six times higher than the average therapeutic level, but there were no signs of severe toxicity. In particular no change in consciousness, electrocardiogram or blood pressure occurred.Pharmacokinetic variables such as dose schedule, steady state kinetics, and metabolism are discussed.     

Methadone Maintenance and Addicts' Risk of Fatal Heroin Overdose

An admission cohort of 296 Australian methadone maintenance patients was followed over 15 years. The relative risks of death in and out of maintenance were calculated for two age groups, 20-29 and 30-39 years. Heroin addicts in both age groups were one-quarter as likely to die while receiving methadone maintenance as addicts not in treatment. This is because they were significantly less likely to die by heroin overdose or suicide while in maintenance. Methadone maintenance had no measurable effect on the risk of death through nonheroin overdose, violence or trauma, or natural causes. A meta-analysis showed the reduction in overall mortality was consistent with the results of cohort studies conducted in the United States, Sweden, and Germany. The combined results of the five studies again indicated that methadone maintenance reduced addicts' risk of death to a quarter, RR 0.25 (95% CI 0.19 to 0.33).     

Serotonin Syndrome Associated with Metaxalone Overdose

Introduction

Serotonin syndrome is a potentially life-threatening entity associated with pro-serotonergic medications in therapeutic use, in overdose, or when co-administered with other drugs. A broad range of drugs and drug combinations have been associated with serotonin syndrome. Metaxalone overdose associated with serotonin syndrome has not been previously reported.

Case Report

(Case 1) A 23-year-old female overdosed on tramadol and metaxalone. She developed dysautonomia, diaphoresis, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, and hyperthermia 5 h after ingestion. Her course was complicated by status epilepticus. (Case 2) A 56-year-old female overdosed on metaxalone and was found unresponsive. She developed dysautonomia, lower extremity rigidity and spontaneous clonus, flaccid upper extremities, rhabdomyolysis, acute renal failure, and hyperthermia. Non-depolarizing neuromuscular blockade and cooling blankets were required to control hyperthermia in both cases. Serum metaxalone levels were markedly elevated in both cases.

Conclusion

These are the first reported cases of metaxalone overdose associated with serotonin syndrome, which may be related to monoamine oxidase inhibition.     

Opioid Overdose Deaths with Buprenorphine Detected in Postmortem Toxicology: a Retrospective Analysis

BackgroundBuprenorphine is a unique μ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited.MethodsA retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures.ResultsOf 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death.ConclusionDecedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.     

Performance of a Multi-disciplinary Emergency Department Observation Protocol for Acetaminophen Overdose

The availability of 20-h N-acetylcysteine (NAC) infusion for low-risk acetaminophen (APAP) overdose enabled our center to implement an Emergency Department observation unit (OU) protocol as an alternative to hospitalization. Our objective was to evaluate our early experience with this protocol. This retrospective cohort study included all patients treated for low-risk APAP overdose in our academic hospital between 2006 and 2011. Cases were identified using OU and pharmacy records. Successful OU discharge was defined as disposition with no inpatient admission. Differences in medians with 95 % confidence intervals were used for comparisons. One hundred ninety-six patients received NAC for APAP overdose with a mean age of 35 years (SD 14); 73 % were white, and 43 % were male. Twenty (10 %) received care in the OU; 3/20(15 %) met criteria for inclusion in the OU protocol and 13/20(65 %) were discharged successfully. Out of the 196 patients, 10 met criteria for inclusion in the OU protocol but instead received care in the inpatient setting. The median total length of stay from presentation to ED discharge was 41 h for all patients treated in the OU, compared to 68 h for ten patients who met criteria for inclusion in the OU protocol but who were admitted (difference 27 h, 95 % CI 18–72 h). ED observation for APAP overdose can be a viable alternative to inpatient admission. Most patients were successfully discharged from the OU. This evaluation identified both over- and under-utilization of the OU. OU treatment resulted in shorter median length of stay than inpatient admission.     

Clinical Outcomes in Newer Anticonvulsant Overdose: A Poison Center Observational Study

Clinicians have limited experience with assessment and treatment of overdose from newer anticonvulsant medications. The aim of this investigation was to evaluate clinical effects of newer anticonvulsant overdose, determine if a relationship exists between dose and clinical effect, and if a particular agent appears more toxic in overdose. This was a retrospective study using electronic poison center data, evaluating clinical outcomes from newer anticonvulsant overdose. The Toxicall™ database from January 1, 2002 to December 31, 2011 was queried using key words: “gabapentin,” “lamotrigine,” “levetiracetam,” “tiagabine,” “topiramate,” “zonisamide,” “pregabalin,” and “oxcarbazine.” Polypharmacy overdose and children less than 15 years of age were excluded. Charts were reviewed by two abstractors for pharmaceutical, self-reported dose, clinical effect score, and clinical signs, symptoms, and vital signs recorded in the chart. Ordinal logistic regression was used to evaluate the relationship between drug type, dose, age, and sex to clinical effect score. Out of 501 cases identified, 347 met the final inclusion criteria. There were 116 gabapentin, 67 lamotrigine, 15 levetiracetam, 15 tiagabine, 56 topiramate, 23 pregabalin, and 55 oxcarbazepine cases. Overdose of newer anticonvulsants frequently results in altered mental status. Seizures may be more common with tiagabine, lamotrigine, and oxcarbazepine. There was one death reported from intentional overdose of topiramate. An information index was created to rank drug toxicity based on reported signs and symptoms for each overdose. There was no significant effect of dose on severity of outcome (β = 0.12, p = 0.23). However, the risk of a more severe outcome score was significantly increased with tiagabine relative to other drugs (β = 2.8, p = 0.001). Lamotrigine ranked highest in terms of toxicity (HT = 1.66) and number of interventions performed (HI = 1.17), and levetiracetam the lowest (HT = 0.98; HI = 0.88). We could not identify a dose-effect in these data which likely reflects the limitations of self-reported doses. Despite limitations of these data, the risk of more severe outcome scores appear to be higher with tiagabine overdose while lamotrigine overdose appears to result in more reported signs, symptoms, and interventions.     

Public health problems and the rapid estimation of the size of the population at risk

Recently, the use of astemizole and terfenadine, both non-sedating H₁-antihistamines, caused considerable concern. Several case reports suggested an association of both drugs with an increased risk of torsades de pointes, a special form of ventricular tachycardia. The increased risk of both H₁-antihistamines was associated with exposure to supratherapeutic doses; for terfenadine the risk was also associated with concomitant exposure to the cytochrome P-450 inhibitors ketoconazole, erythromycin and cimetidine. To predict the size of the population that runs the risk of developing this potentially fatal adverse reaction in the Netherlands, the prevalence of prescribing supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome P-450 inhibitors was studied. Data were obtained from the PHARMO data base in 1990, a pharmacy-based record linkage system encompassing a catchment population of 300,000 individuals. The results of the study showed that the prescribing of supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome P-450 inhibitors was low. Furthermore, the results of a sensitivity analysis showed that the risk of fatal torsades de pointes has to be as high as 1 in 10,000 to cause one death in the Netherlands in one year.     

Bupropion Induced Serotonin Syndrome: A Case Report

Although there are no documented cases of serotonin syndrome (SS) following bupropion ingestion alone in the literature, the ability of bupropion to potentiate serotonin levels and lead to SS is known. A 15-year-old boy was found at home hallucinating. He then developed tonic–clonic activity. Upon arrival in the emergency department, he was confused and restless. On exam, he had tachycardia, hypertension, dilated pupils and dry oral mucosa, normal tone and reflexes in his arms, but rigidity and +4 reflexes in his legs with sustained clonus at his ankles. He was admitted and treated with intravenous fluids and lorazepam for his agitation. A urine drug screen (via gas chromatography/mass spectrometry) was positive only for naproxen and bupropion. Serum bupropion and hydroxybupropion levels drawn 17 h after his reported ingestion were 280 (therapeutic range 50–100) and 3,100 ng/mL (therapeutic range <485), respectively. Within 24 h of his admission, the patient was awake with normal vital signs and neurologic exam. To our knowledge, there are only three reported cases demonstrating SS in conjunction with bupropion toxicity; however, none of these were secondary to bupropion alone.     

Citalopram: Clinical effect profile in comparison with clomipramine. A controlled multicenter study

The selective serotonin reuptake inhibitor citalopram was compared with clomipramine in a multicenter clinical study. From a total of 150 depressed patients (age 18–65 years), 114 patients with a Hamilton Depression Scale (HDS) total score18 at the end of a 1 week placebo period were started on treatment with either citalopram (40 mg/day) or clomipramine (150 mg/day) (fixed, single daily dose). Patients stratified according to diagnostic rating (Newcastle Inventory, endogenous/non-endogenous) were randomly allocated to treatment groups using double blind principles. In total, 102 patients completed more than 2 weeks, treatment and were included in the analyses of therapeutic effect. The two drug groups were comparable in terms of sex, age, and departmental distribution.Categorical measurements of therapeutic effect based on the HDS total score showed that in the endogenously depressed patients a significantly higher percentage of patients on clomipramine (n=37) than on citalopram (n=38) were classified as complete responders (HDS total7) after 3, 4 and 5 weeks of treatment. In the non-endogenously depressed patients (clomipramine: n=15, citalopram: n=12) rather similar numerical differences were observed (P<0.05 at 5th week). In the total patient group the percentage of complete response after 5 weeks was about 60 in the clomipramine group (n=52) and about 30 in the citalopram group (n=50) (P<0.005). The better effect of clomipramine seemed to be related in particular to the sleep items, but other items covering depression, retardation and anxiety/agitation also contributed to the difference in total score that was also seen in patients with low initial scores on the sleep items.Citalopram was devoid of the typical autonomic side effects and orthostatic hypotension seen with clomipramine. Symptoms of nausea/vomiting and headache became somewhat worse in the citalopram- and somewhat better in the clomipramine-treated patients. Participating centers: ¹Department of Psychiatry, Odense University Hospital, Odense, ²Department of Psychiatry, Rigshospitalet, University of Copenhagen, Copenhagen, ³Departments of Psychiatry, Frederiksborg General Hospital, Hillerød, ⁴Department A and C, Psychiatric University Hospital, Århus, ⁵Department of Psychiatry, Bornholm General Hospital, Rønne, ⁶Department of Clinical Pharmacology, Odense University, Odense Participating clinicians: J. Andersen², P. Bech^2,3, S. Benjaminsen¹, M. Bjerre¹, S. Bøjholm⁵, P. Christensen¹, A. Gjerris², L. Hansted⁴, E. Jensen³, P. Kragh-Sørensen¹, C.B. Kristensen^1,3, P. Kyneb⁴, D. Loldrup³, O.F. Madsen⁴, O.L. Pedersen¹, O.J. Rafaelsen², S. Rasmussen³, N. Reisby⁴, F. Sevaj³, P. Simonsen⁴, H.Y. Thomsen¹, P. Vestergaard⁴ Coordination and drug assay: L.F. Gram⁶ Statistical consultants: O. Aaskoven, P. Allerup Data-collection and -processing: C. Sánchez Steering Committee: P. Bech, L.F. Gram (chairman), P. Kragh-Sørensen, O.J. Rafaelsen, N. Reisby, P. Vestergaard Danish University Antidepressant Group     

The Kinetics of Citalopram: Single and Multiple Dose Studies in Man

Abstract: The kinetics of citalopram were studied in a group of volunteers after oral (8 subjects) and intravenous (4 subjects) single doses and repeated oral administration (7 subjects). Inter- and intraindividual variation was limited and linearity of kinetics indicated. Systemic and apparent oral clearance estimates (mean 0.42 1 plasma/min.) were similar, indicating roughly complete systemic availability. The presence of unchanged drug in urine, corresponding to 1/7 of the dose, suggests elimination by renal as well as hepatic processes. The data from the intravenous test revealed two compartment kinetics; the total volume of distribution was estimated to about 11501 and that of the central compartment to 1751. Upon repeated administration steady-state conditions were generally achieved after one week in agreement with the 33 hrs half-life of elimination. Citalopram peak concentrations were reached within 2–4 hrs after the daily dose and maximally two-fold variation was recorded in the 24 hrs dose interval. The levels of a main pharmacodynamically active metabolite were roughly half as high as the drug levels.     

西酞普兰与文拉法辛治疗抑郁症的临床对照研究

目的:比较西酞普兰与文拉法辛治疗抑郁症的效果及不良反应。方法:收集符合CCMD3抑郁症诊断标准的门诊患者57名,随机分为西酞普兰组(n=29)和文拉法辛组(n=28)。西酞普兰组服用剂量为每日20～40mg,文拉法辛组服用剂量为每日50～300mg,观察期限为7周。采用HAMD、SDS和临床4级疗效评定法同时进行疗效评定,采用TESS不良反应量表评定不良反应。结果:治疗后7周末评定结果显示,两组SDS总分、HAMD总分及7个因子分均比治疗前有显著下降(P<0.01)。两组的有效率相似,分别为93%(西酞普兰组)和89%(文拉法辛组)两者比较,无显著差异(P>0.05)。两组的不良反应格局大体相似,程度轻微,患者均能耐受。结论:西酞普兰和文拉法辛治疗抗抑郁症的作用相似,不良反应轻微,临床运用安全。     

Prolonged Toxicity after Amitriptyline Overdose in a Patient Deficient in CYP2D6 Activity

Introduction

Amitriptyline and its metabolite, nortriptyline, are metabolized, in part, by CYP2D6, a polymorphic enzyme. About 8% of Caucasians are deficient in CYP2D6 activity.

Case Report

We present the case of a comatose woman who intentionally overdosed on amitriptyline and displayed rising serum total tricyclic antidepressant concentrations for at least 6 days after admission. Serial immunoassay total tricyclic antidepressant concentrations in our patient showed gradual decline beginning day 7, although the patient did not regain normal mental status until day 12. Genotyping revealed the patient to be homozygous for the CYP2D6*4 allele, the most common explanation of CYP2D6 enzymatic deficiency among Caucasians. Patients taking tricyclic antidepressants who are homozygous for CYP2D6*4 demonstrate >3 times concentration–time curve (AUCs) and prolonged elimination half-lives, especially of secondary amines such as nortriptyline.

Discussion

We believe this is the first report describing toxicokinetics after tricyclic antidepressant overdose in a CYP2D6-deficient patient.     

Acute on Chronic Ivabradine Overdose: a Case Report

Ivabradine is a newly approved medication which reduces the heart rate by antagonizing the I_f channel. We report a case of intentional overdose on ivabradine. A 26-year-old female presented after taking 250 mg ivabradine. On arrival, her vital signs and neurologic exam were unremarkable. Within 30 min, her heart rate decreased to 31 bpm, but she remained normotensive with no change in mentation. Her bradycardia resolved after treatment with atropine. She experienced two further bradycardic episodes responsive to atropine; the second episode was associated with hypotension, responsive to a fluid bolus. For the remainder of her hospitalization, she remained hemodynamically stable without further interventions. She was dispositioned to the psychiatry service approximately 36 h post-ingestion with a heart rate of 67 bpm. Laboratory analysis confirmed a serum ivabradine concentration of 525 ng/mL, greater than 50 times the mean level in therapeutic trials. Proposed treatments for ivabradine include activated charcoal, atropine, isoproterenol, and intravenous pacing. Further study is needed to identify ideal treatment modalities.     

High Prevalence of Self-Reported Exposure to Adulterated Drugs Among People Who Experienced an Opioid Overdose in Canada: A Cohort Study

Background: In North America, rates of overdoses are increasing largely due to the adulteration of illicit drugs by illicit synthetic opioids. Objectives: We sought to examine the prevalence and correlates of self-reported exposure to adulterated drugs among people who experienced a non-fatal opioid overdose. Methods: Data were derived from three prospective cohort studies of people who use drugs in Vancouver, Canada between June and November 2016. Multivariable logistic regression analyses were used to examine the prevalence and correlates of self-reported exposure to adulterated drugs. Results: Among 117 participants who reported symptoms consistent with a non-fatal opioid overdose, 78 (66.7%) reported believing the drug was adulterated during their last overdose. Of those, 42 (53.8%) had not perceived adulteration prior to overdose. In the multivariable analysis, engagement in opioid agonist therapy (Adjusted Odds Ratio [AOR]?=?2.79, 95% Confidence Interval [CI]: 1.10, 7.45) was independently associated with having not perceived adulteration prior to overdose. Daily heroin use (AOR = 5.28; 95% CI: 1.92, 15.97) and reporting supervised injection site staff were present at most recent overdose (AOR = 6.16; 95% CI: 1.25, 47.27) were independently associated with having perceived adulteration prior to overdose. Conclusions/Importance: We found a high prevalence of believing adulterated drugs were present for the most recent overdose. Further, the high prevalence of unperceived adulteration prior to overdose supports the need to lower the risk of overdose by providing individuals with options to consume drugs in a safer manner, including supervised consumption sites.     

Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France

AIMS

The aim of this study was to investigate the incidence and reporting rate of drug-induced long-QT syndrome (LQTS) in France [defined by evidence of torsades de pointes (TdP), QT prolongation and exposure to a relevant drug] and to assess feasibility of case collection for drug-induced LQTS.

METHODS

A retrospective population-based study was carried out in Southwest France in five institutions: three main hospitals, one private clinic and one cardiac emergency unit, searched from 1 January 1999 to 1 January 2005 (population coverage of 614 000). The study population consisted of 861 cases with International Classification of Diseases-10 diagnostic codes for ventricular tachycardia (I147.2), ventricular fibrillation (I149.0) and sudden cardiac death (I146.1) from hospital discharge summaries, supplemented by cases reported to national or regional pharmacovigilance systems, and voluntary reporting by physicians, validated according to internationally defined criteria for drug-induced LQTS.

RESULTS

Of 861 patients coded with arrhythmias or sudden cardiac death, there were 40 confirmed surviving acquired cases of drug-induced LQTS. We estimated that the incidence of those who survive to reach hospital drug-induced LQTS is approximately 10.9 per million annually in France (95% confidence interval 7.8, 14.8).

CONCLUSIONS

Many cases of drug-induced LQTS may not survive before they reach hospital, as the reporting rate for drug-induced LQTS identified through the cardiology records and also reported to pharmacovigilance systems for the Midi-Pyrenees area is 3/40 (7.5%). Using the methods outlined it is possible to assemble cases to study genetic susceptibility to drug-induced LQTS and adapt these methods more widely.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Drug-induced long-QT syndrome (LQTS) is a potentially fatal condition that has led to a number of postmarketing withdrawals in recent years.
• However, many cases may not survive long enough to reach hospital, and only a small proportion are reported to pharmacovigilance agencies.
• The extent to which genetic determinants of susceptibility to LQTS are specific to particular drugs, or common to several classes of drug, remains to be determined.

WHAT THIS STUDY ADDS

• We estimated population prevalence of drug-induced LQTS in the Midi-Pyrenees region, southwest France, using five different institutions and assessed feasibility of tracing potential cases (in addition to pharmacovigilance data), using hospital data and rigorous case definition.
• These methods can be adapted to a wider region, used to augment pharmacovigilance reporting, and offer researchers the opportunity to study genetic susceptibility to drug-induced LQTS.

     

Socio-Demographic Profile and Hiv and Hepatitis C Prevalence Among Persons Who Died of a Drug Overdose

To describe the sociodemographic characteristics and HIV and Hepatitis C prevalence among persons who died of a drug overdose in the Vancouver metropolis health region in 1998. Methods: A retrospective review was conducted on all overdose death files in the Vancouver/Richmond health region reported to the Office of the Chief Coroner. The files included, autopsy, toxicology, virology, and coroner reports. External linkages were done to determine the proportion of individuals on antiretro-viral treatment. Contingency analyses were conducted to determine factors associated with Hepatitis C and HIV seropositivity. Results: Data on a total of 199 deaths were obtained from the coroner's office. Of these 37 (18.6%) were female and 162 (81.4%) were male. A total of 25 (12.6%) deaths were among persons of First Nations descent and 134 (73.6%) were among chronic drug users. The median age at death was 38 years (Interquartile range [IQR]: 32–45 years). The drug most commonly responsible for overdose was heroin [89 (47.3%) deaths]. A total of 91 (45.7%) deaths were tested for HIV and 95 (47.7%) deaths were tested for HCV. Of those deaths, 28 (29.8%) were HIV-positive and 78(78.0%) were HCV-positive. Conclusion: Our analysis suggests that those dying of illicit drug overdose in Vancouver during 1998, are largely comprised of older, male, chronic injection drug users. Rates of HIV and HCV positivity are very high in this group.     

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

Introduction

4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission. This medication has been studied and used in many disease processes hallmarked by poor neuronal transmission in both the central and peripheral nervous systems including: multiple sclerosis (MS), spinal cord injuries (SCI), botulism, Lambert-Eaton syndrome, and myasthenia gravis. It has also been postulated as a potential treatment of verapamil toxicity and reversal agent for anesthesia-induced neuromuscular blockade. To date, there have been limited reports of either intentional or accidental 4-AP toxicity in humans. Both a case of a patient with 4-AP toxicity and review of the literature are discussed, highlighting commonalities observed in overdose.

Case Report

A 37-year-old man with progressive MS presented with diaphoresis, delirium, agitation, and choreathetoid movements after a presumed 4-AP overdose. 4-AP concentration at 6 h was 140 ng/mL. With aggressive benzodiazepine administration and intubation, he recovered uneventfully.

Discussion

The commonalities associated with 4-AP toxicity conforms to what is known about its mechanism of action combining cholinergic features including diaphoresis, altered mental status, and seizures with dopamine-related movement abnormalities including tremor, choreoathetosis, and dystonia. Management of patients poisoned by 4-AP centers around good supportive care with definitive airway management and controlling CNS hyperexcitability aggressively with gamma-aminobutyric acid agonist agents. Adjunctive use of dopamine antagonists for extrapyramidal effects after sedation is a treatment possibility. As 4-aminopyridine recently received Federal Drug Administration approval for the treatment of ambulation in patients with MS, physicians should be keenly aware of its presentation, mechanism of action, and management in overdose.