Simultaneous determination of paracetamol, dextromethorphan, chlorpheniramine, pseudoephedrine and major impurities of paracetamol and pseudoephedrine by using capillary electrophoresis

Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.

Eficacia de la miel para el tratamiento de la tos aguda en niños atendidos en forma ambulatoria / Efficacy of honey for treatment of acute cough in pediatric outpatients

A partir de una consulta en la central de emergencias de un niño con tos aguda, el autor del artículo realiza una búsqueda bibliográfica para revisar la evidencia sobre el uso de la miel para aliviar este síntoma. Luego de la lectura crítica de una revisión sistemática, el autor concluye que ésta podría ser una alternativa elegible frente a los jarabes para la tos, por su perfil de seguridad y su posible beneficio en el alivio de la tos. (AU)

Based on a consultation at the emergency room of a child with acute cough, the author of this article performs a bibliographic search to review the evidence on the use of honey to alleviate this symptom. After the critical appraisal of a systematic review, the author concludes that honey could be an eligible alternative to cough syrups, due to its safety profile and its possible benefit in cough relief. (AU)

Management of the pseudobulbar affect (PBA) in Kabuki syndrome combined dextromethorphan-fluoxetine treatment as an alternative to dextromethorphan/quinidine

A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global Impression-Improvement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) ­ especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It's could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary. (AU)

Improved Bulbar Function in Amyotrophic Lateral Sclerosis after Nuedexta (Dextromethorphan and Quinidine) Treatment

Nuedexta (dextromethorphan and quinidine) is an Food and Drug Administration approved medication for pseudobulbar affect. Interestingly, this drug was recently reported to improve speech, swallowing, and the ability to handle oral secretions along with emotional lability in amyotrophic lateral sclerosis (ALS) patients with bulbar symptoms. We report a Korean ALS patient whose bulbar function improved after administering Nuedexta for 6 months, extending therapeutic choice of approach in treating ALS patients.

Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

Prediction and visualization of CYP2D6 genotype-based phenotype using clustering algorithms

This study focused on the role of cytochrome P450 2D6 (CYP2D6) genotypes to predict phenotypes in the metabolism of dextromethorphan. CYP2D6 genotypes and metabolic ratios (MRs) of dextromethorphan were determined in 201 Koreans. Unsupervised clustering algorithms, hierarchical and k-means clustering analysis, and color visualizations of CYP2D6 activity were performed on a subset of 130 subjects. A total of 23 different genotypes were identified, five of which were observed in one subject. Phenotype classifications were based on the means, medians, and standard deviations of the log MR values for each genotype. Color visualization was used to display the mean and median of each genotype as different color intensities. Cutoff values were determined using receiver operating characteristic curves from the k-means analysis, and the data were validated in the remaining subset of 71 subjects. Using the two highest silhouette values, the selected numbers of clusters were three (the best) and four. The findings from the two clustering algorithms were similar to those of other studies, classifying *5/*5 as a lowest activity group and genotypes containing duplicated alleles (i.e., CYP2D6*1/*2N) as a highest activity group. The validation of the k-means clustering results with data from the 71 subjects revealed relatively high concordance rates: 92.8% and 73.9% in three and four clusters, respectively. Additionally, color visualization allowed for rapid interpretation of results. Although the clustering approach to predict CYP2D6 phenotype from CYP2D6 genotype is not fully complete, it provides general information about the genotype to phenotype relationship, including rare genotypes with only one subject.

Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress / 药学学报

This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.

Borneol is an inducer of rat hepatic CYP2D activity in vivo / 药学学报

Borneol is a traditional Chinese medicine. In the past few years, many studies showed that borneol can improve the bioavailability of other drugs, promoting drugs to cross the blood-brain barrier, so the potential drug interactions between borneol and other medicines have attracted great attention, but the influence of borneol to CYP450 and its isoforms are rarely reported. In this research, male Wistar rats were orally administered by borneol for 7 days, then the mRNA and protein expression and the activities of CYP2D were detected, we also compared the pharmacokinetic parameters of CYP2D's specific substrate between control group and borneol group. The results show that borneol (33, 100 and 300 mg x kg(-1) x d(-1)) have no significant effect on CYP2D, while the activites of CYP2D increased 1.71, 1.97 and 2.89 times comparing to the control group. At the same time, borneol (300 mg x kg(-1) x d(-1)) caused the C(max) decreased 10.6% (P > 0.05), AUC(0-∞) decreased 27.5% (P < 0.01), CL/F increased 41.1% (P < 0.01), V(z)/F increased 23.1% (P > 0.05) of dextromethorphan. Our data provided that borneol speed up dextromethorphan's elimination in vivo. Since the activity of CYP2D can be induced by borneol, the metabolic interactions might happen when borneol and the substrate drug CYP2D are used together.

CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.</p><p><b>METHOD</b>Cocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes.</p><p><b>RESULT</b>Compared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).</p><p><b>CONCLUSION</b>Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.</p>

Serotonin Syndrome After an Overdose of Dextromethorphan and Chlorpeniramine: Two Case Reports

Dextromethorphan and chlorpeniramine are common ingredients of over-the-counter (OTC) cough pills. They are known to be safe when used alone, however, combination with other serotonergic drugs or use of an overdose can cause serotonergic toxicity. We report on a 43-year-old male and a 57-year-old female who ingested an overdose of antitussive drugs containing dextromethorphan and chlorpeniramine. They commonly presented with altered mentality and hyperreflexia on both upper and lower extremities. After conservative therapies, they were discharged with alert mentality. These cases are meaningful in that there are few cases of serotonin syndrome with an overdose of a combination of dextromethorphan and chlorpeniramine. Careful use with medication counseling for OTC cough pills is needed in order to prevent overdose of these ingredients.

Tosse: neurofisiologia, métodos de pesquisa, terapia farmacológica e fonoaudiológica / Cough: neurophysiology, methods of research, pharmacological therapy and phonoaudiology

Introdução: A tosse é o sintoma respiratório mais comum em crianças e adultos. Objetivo: Apresentar uma revisão sobre a neurofisiologia e os métodos para estudo do reflexo da tosse, bem como a farmacoterapia e terapia fonoaudiológica da tosse, baseada nos trabalhos publicados entre 2005 e 2010 e indexados nas bases Medline, Lilacs e Biblioteca Cochrane sob os unitermos "tosse" ou "antitussígenos". Síntese dos dados: O reflexo da tosse envolve ativação de múltiplos receptores vagais nas vias aéreas e de projeções neurais do núcleo do trato solitário para outras estruturas do sistema nervoso central. Técnicas experimentais permitem estudar o reflexo da tosse ao nível celular e molecular para desenvolver novos agentes antitussígenos. Não há evidências de que antitussígenos isentos de prescrição médica tenham eficácia superior à do placebo para o alívio da tosse. A terapia fonoaudiológica pode beneficiar pacientes com tosse crônica refratária ao tratamento farmacológico, sobretudo quando coexiste movimento paradoxal das pregas vocais. Comentários Finais: A abordagem multidisciplinar tem papel fundamental no diagnóstico etiológico e tratamento da tosse. O otorrinolaringologista deve informar os pacientes sobre os riscos dos antitussígenos de venda livre a fim de prevenir intoxicações e efeitos adversos, especialmente em crianças...

Introduction: The cough is the more common respiratory symptom in children and adults. Objective: To present a revision on the neurophysiology and the methods for study of the consequence of the cough, as well as the pharmacotherapy and phonoaudiology therapy of the cough, based on the works published between 2005 and 2010 and indexed in the bases Medline, Lilacs and Library Cochrane under them to keywords "cough" or "anti-cough". Synthesis of the data: The consequence of the cough involves activation of receiving multiples becomes vacant in the aerial ways and of neural projections of the nucleus of the solitary treatment for other structures of the central nervous system. Experimental techniques allow studying the consequence of the cough to the cellular and molecular level to develop new anti-cough agents. It does not have evidences of that anti-cough exempt of medical lapsing they have superior effectiveness to the one of placebo for the relief of the cough. The phonoaudiology therapy can benefit patients with refractory chronic cough to the pharmacological treatment, over all when paradoxical movement of the vocal folds coexists. Final Comments: The boarding to multidiscipline has basic paper in the etiological diagnosis and treatment of the cough. The otolaryngologist must inform the patients on the risks of the anti-cough of free sales in order to prevent adverse poisonings and effect, especially in children...

CYP2D6*1, CYP2D6*10 co-expressed with CYPOR in Bac-to-Bac expression system and activity determination / 药学学报

CYP2D6 is an important drug-metabolizing enzyme. The polymorphism of CYP2D6 leads to metabolism difference and the different reactions of drugs in the individuals and different races are normal phenomenon in clinical medication. CYP2D6*10 is an important subtype in Asian people and 51.3% Chinese are classified with this subtype. To obtain recombinant active CYP2D6*1/CYP2D6*10 in baculovirus system by optimizing coexpression with CYPOR, and detect their activity to catalyze dextromethorphan, three recombinants pFastBac-CYP2D6*1, pFastBac-CYP2D6*10 and pFastBac-CYPOR were constructed and transformed into DH10Bac cell to obtain the recombinant Bacmid-CYPOR, Bacmid-CYP2D6*1 and Bacmid-CYP2D6*10. And then the recombinant CYP2D6*1 and CYP2D6*10 virus were obtained by transfecting Sf9. Then homogenate protein activity was determined with dextromethorphan as substrate. The multiple of infection (MOI) and its ratio of recombinant CYP2D6 virus to CYPOR virus were adjusted by detecting the activity of the homogenate protein. The Km and Vmax are 26.67 +/- 2.71 micromol x L(-1) (n=3) and 666.7 +/- 56.78 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*1 to catalyze dextromethaphan. The Km and Vmax are 111.36 +/- 10.89 micromol x L(-1) (n=3) and 222.2 +/- 20.12 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*10 to catalyze dextromethorphan. There is significant difference between CYP2D6*1 and CYP2D6*10 for Vmax and Km (P < 0.01). The clearance ratio of CYP2D6*1 is 25.0 and the clearance ratio of CYP2D6*10 is 2.0. The expressed CYP2D6*1 and CYP2D6*10 are useful tools to screen the metabolism profile of many xenobiotics and endobiotics in vitro, which are benefit to understand individual metabolism difference.

CYP2D6 genotypes and phenotypes in Chinese Han, Uygur and Kazakh populations / 药学学报

This study is to compare the influence of CYP2D6 *3 and *4 genotypes and phenotypes on the metabolic activity of CYP2D6 in Chinese Han, Uygur and Kazakh ethnic groups. Allele specific amplification (ASA) was used to determine the CYP2D6*3 and CYP2D6*4 genotypes. Phenotypes of CYP2D6 in all subjects were determined using dextromethorphan as probe drug by HPLC methods. Among the 132 Han subjects, one subject (0.76%) exhibited the *1/*3 combination, and one (0.76%) exhibited the *1/*4. Among the 136 Uygur subjects, 4 subjects (2.94%) showed the *1/*3 combination, 12 (8.82%) showed *1/*4, 4 (2.94%) showed *4/*4, and one (0.74%) showed *3/*4. Among the 116 Kazakh subjects, 2 (1.72%) exhibited the *1/*3 combination, 7 (6.03%) exhibited *1/1*4, and one (0.86%) showed *4/*4. This research revealed significant differences in the occurrence frequencies of the CYP2D6 genotype between Han and Uygur ethnic groups, as well as between Uygur and Kazakh populations. However, no difference was found between Han and Kazakh populations. In addition, the prevalence of PMs of the Uygur is comparable to that of the Caucasians. However, the molecular mechanism underlying the poor metabolism is different in these two populations.

Pharmacokinetic study of a new chewing gum dextromethorphan delivery system / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish an high-performance liquid chromatography (HPLC)-based method for analysis of the pharmacokinetics and relative bioavailability of dextromethorphan chewing gum tablets in rabbits.</p><p><b>METHODS</b>The pharmacokinetic parameters and the relative bioavailability of dextromethorphan chewing gum preparation in rabbits were compared with those of the commercially available chewing dextromethorphan tablets using 3P97 software.</p><p><b>RESULTS</b>Pharmacokinetic analysis of the new dextromethorphan chewing gum tablets showed a AUC of 488.76 ∓ 175.00 ng.ml(-1).h, C(max) of 95.45 ∓ 17.53 ng/ml, and t(max) of 1.83 ∓ 0.57 h as compared with the corresponding parameters of 370.13 ∓ 90.56 ng.ml(-1).h, 174.00 ∓ 47.88 ng.ml, and 1.04 ∓ 0.14 h for the commercially available chewing tablets. The relative bioavailability of the new chewing gum medicine system was (140.73 ∓ 65.91)%.</p><p><b>CONCLUSION</b>The new dextromethorphan chewing gum preparation shows an increased AUC((0→)), decreased C(max), and prolonged t(max) in comparison with the commercially available chewing tablets, with also a greatly enhanced relative bioavailability.</p>

Normal-phase LC method for simultaneous analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in tablet formulation

A simple, precise, and accurate method and validated for the analysis of pseudophedrin hydrochloride, dextromethrophan hydrobromide chlorpheniramine maleate, and paracetamol in tablet formulations. The method has shown adequate separation of the four ingredients from each other. Separation was achieved on a silica column [5 micro m, 125 X 4,6 mm inner diameter] using a mobile phase consisting of methanaol/ammonium dihyddrogen phosphate buffer [90:10, v/v] at a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is validated in accordance with USP requirements for new methods for assay determination, which include accuracy, precision, selectivity, linearity and range, probustness and ruggedness. The current method demonstrates good linearity over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r[2] of 0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide with r[2] of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine maleate with r[2] of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol with r[2] of 0.991. The average recovery of the method is 99.7%, 98.1%, and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide, chlorpheniramien maleate, and paracetamol, respectively. The degree of reproducibility of the results obtained as a result of small deliberate variations in the method parameters and by changing analytical operator has proven that the method is robust and rugged

Screening of codeine, dextromethorphan & dextropropoxyphene for their genotoxicity in swiss albino mice.

Background & objectives: It is mandatory for all new drugs to be tested for their potential genotoxicity in addition to general toxicity testing. Some old drugs have not been tested adequately for their genotoxic effects as these were in use before the regulations were enforced. The present study therefore aims to explore the genotoxic potential of some commonly used opioids like codeine, dextromethorphan and dextropropoxyphene in swiss albino mice. Methods: Therapeutic equivalent doses of codeine, dextromethorphan and dextropropoxyphene were given orally. Single dose for acute study and multiple doses (repeated every 24 h for 7 times) in additional groups of mice (n=5 in each) for subacute study. Cyclophosphamide served as positive control while normal saline as negative control. About 0.5 ml of blood was collected by retroorbital sinus for comet assay and later the mice were sacrifi ced to aspirate the femoral bone marrow for micronucleus test. Percentage of micronucleated polychromatic erythrocytes (MnPCE) and comet tail length were calculated in micronucleus assay and comet assay respectively, which served as markers of genotoxicity. Results: Signifi cant Signififi (P<0.001) increase in comet tail length and % MnPCE was observed in both acute and subacute studies of cyclophosphamide group, whereas codeine, dextromethorphan and dextropropoxyphene treated groups did not show any signifi cant changes. Interpretation & conclusion: The results indicated that codeine, dextromethorphan and dextropropoxyphene were devoid of genotoxicity in mice.

[Comparison of the effects of preemptive gabapentin and dextromethorphan on the postoperative pain after open prostatectomy]

Preemptive administration of gabapentin and dextromethorphan has been shown to be effective for reduction of postoperative pain; but the effect of these two drugs has not yet been compared. The aim of the present study was to compare the effects of administration of gabapentin and dextromethorphan on the postoperative pain after open prostatectomy. In a randomized clinical trial, 80 adult males with ASA class of I, II and III who were candidate for open prostatectomy under spinal anesthesia in Shahid Hasheminejad Educational Center [in Tehran] were enrolled and randomly allocated to two groups of gabapentin [n=40] and dextromethorphan [n=40]. In dextromethorphan group, 60 mg of dextromethorphan syrup and in gabapentin group, 300 mg of gabapentin syrup were administered 2 hours preoperatively. During operation, the maximum height of block was determined at 5, 10 and 15 minutes after spinal anesthesia establishment. In postoperative period, at 1, 2, 12, and 24 hours, the pain intensity was measured through Visual Analogue Pain Scale [VAS]; and, overall opioid consumption and the time to first analgesic request were recorded as well. While the pain intensity in all the measurements was comparable between groups, at the 2nd hour, the pain was significantly lesser in gabapentin group [2.70 +/- 1.51 vs. 3.74 +/- 1.77, P=0.006]. Also, the time for the first analgesic request was comparable between study groups; however, the total dose of postoperative opioid consumption was lesser in gabapentin group [45.0 +/- 39.32 vs. 64.45 +/- 32.12 mg, P=0.018]. Moreover, the height of block showed no significant difference. Preemptive oral administration of 300 mg of gabapentin syrup in patients undergoing open prostatectomy under spinal anesthesia significantly lessens the pain intensity and the total dose of opioid consumption compared with 60 mg of dextromethorphan syrup. Meanwhile, the level of spinal anesthesia and the time for the first analgesic request were comparable between groups

Effects of dextromethorphan on dopamine dependent behaviours in rats.

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.

Excessive crying and irritability in infants due to drugs

This study was performed to see the extent and magnitude of drug induced excessive crying in infants and to know the causative drugs, from July 2005 to June 2006. It is a prospective and descriptive study. All children under 1 year of age, who presented with excessive crying of recent onset as the main complaint and were receiving some medicines were included in the study. After getting detailed history [particularly drug history], the problem was explained to the parents, the suspected drug was stopped and the patients were called back for follow up after 48-96 hours. If the crying had not stopped, the diagnosis was reconsidered and patient was excluded from study analysis. If the crying had stopped, it was assumed that the drug was the cause of excessive crying. All the included patients were studied for age, diagnosis, month of the year, geographical origin and the causative drugs. A total of 227 patients were included in the analysis; out of this, 44 [19.38%] were less than imonth of age while 183 patients [80.62%] were above 1 month, 143 patients were suffering from upper respiratory infection and 78 from wheezy chest. Majority of the patients presented during winter months. About 3/4th of the patients were from D. I. Khan district but the remaining 1/4th were from nearby and remote districts like Mianwali and Layyah. Most frequent causative drug was Rondec-D drops [Abbot] in 13o patients. Other drugs were various cough preparations, promethazine [Phenergan], brochodilators, anti-emetics, metronidazole, anti-histamines, various herbal preparations, phenolbarbitone and various anti-diarrhoeals in a decreasing order of frequency. This problem can be reduced by avoiding these medicines in below 1-2 years of age. It is therefore recommended that these above drugs should not be promoted for use in infants and Rondec-D drops and other similar preparations may be withdrawn from the market