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   Table of Contents - Current issue
Coverpage
April-June 2018
Volume 9 | Issue 2
Page Nos. 63-120

Online since Tuesday, September 4, 2018

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EDITORIAL  

Supplementary protection certificates are detrimental to medicine affordability p. 63
Vijay Thawani
DOI:10.4103/jpp.JPP_68_18  
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REVIEW ARTICLES Top

Comprehensive review on methadone-induced QT prolongation and torsades p. 66
Jennifer M Treece, Mohammad Al Madani, George El Khoury, Ola Khraisha, James E Martin, Steven J Baumrucker, Christopher A Neglia, Timir K Paul
DOI:10.4103/jpp.JPP_163_17  
An alternative analgesic to morphine is methadone, which is used to control chronic pain and is used in opioid rehabilitation treatment programs due to methadone having a long half-life and being relatively inexpensive as compared to extended-release forms of morphine. Despite its benefits, methadone accumulates in adipose tissue due to being lipophilic, binds strongly to plasma proteins, and is metabolized in the liver by the cytochrome P450 system causing methadone levels to be variable and subject to influence according to the individual body compositions and concurrent use of cytochrome P450 inhibitors. In addition to methadone being able to cause both respiratory and central nervous system depression, methadone can also prolong the QT interval and cause potentially life-threatening arrhythmias including torsades de pointes. The susceptibility of unintentional overdosing of methadone due to its varied pharmacologic properties and potentially fatal induction of arrhythmias may cause the risks of methadone use to outweigh its benefits and therefore must be closely monitored.
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Terlipressin-Induced ischemic complications: A systematic review of published case reports p. 76
Phulen Sarma, Gaurav Muktesh, Rahul Solomon Singh, Abhishek Mishra, Ashutosh Singh, Rakesh Kumar Ruhela, Harish Kumar, Narendra Dhaka, Bikash Medhi
DOI:10.4103/jpp.JPP_23_18  
Terlipressin is used in the management of variceal bleeding and hepatorenal syndrome. Ischemic complications are rare, but serious adverse effects of terlipressin therapy can be fatal. In this context, we reviewed all the published case reports of terlipressin-induced ischemic complications, and data were collected regarding the part of body affected by ischemic complication, latency, geographical variation, different treatment strategies and their outcome, and other relevant information. After an exhaustive search in different databases, 33 published cases were found. The ischemic complications affected virtually every part of the body. Peripheral gangrene was the most common ischemic complication followed by ischemic complications of more proximal parts such as thigh and abdominal wall. Other parts affected were heart, colon, small intestine, scrotum, etc. Most cases were managed conservatively. Although in few cases, other treatment options were also explored, knowledge of this dreaded complication and different management strategies is necessary for early identification of this adverse effect and early management so as to prevent fatality.
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RESEARCH PAPERS Top

Frequency of chemotherapy medication errors: A systematic review p. 86
Ramkumar Ashokkumar, Sureshkumar Srinivasamurthy, Janet J Kelly, Scott C Howard, Subramani Parasuraman, Chakradhara Rao S. Uppugunduri
DOI:10.4103/jpp.JPP_61_18  
Objective: To synthesize peer-reviewed knowledge on the frequency of different types of chemotherapy medication errors. Methods: The data were collected from studies published between January 1, 2000, and March 3, 2018, and are identified through online resources such as Medline/PubMed, PubMed Central, Agency for Healthcare Research, and Quality and the Cochrane Library. The manuscripts published in peer-reviewed scientific journals in English language were included in the study. Initially, 19,723 articles were retrieved and finally 11 were found to be eligible to include in the review and were assessed for quality. Error percentages were calculated from the ratio of error type (numerator) to sample size (denominator: medication orders or prescriptions). Results: Overall, the chemotherapy medication errors ranged from 0.004% to 41.6% among various studies. Chemotherapy medication errors ranged from 0.1% to 24.6% in prescribing, 0.40% to 0.50% in preparation, 0.03% in dispensing, and 0.02% to 0.10% in administering phases. Conclusion: Prescribing phase had the highest number of chemotherapy medication errors reported, and least was reported during dispensing phase. We also noticed a need for harmonization for reporting of medication errors.
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Investigation of hERG1b influence on hERG channel pharmacology at physiological temperature p. 92
Aziza El Harchi, Dario Melgari, Henggui Zhang, Jules C Hancox
DOI:10.4103/jpp.JPP_158_17  
Objective: To compare the inhibitory potencies of selected drugs (chloroquine, fluoxetine, cisapride, and ebastine [EBA]) on human Ether-a-go-go-Related Gene (hERG) potassium channel current carried by either hERG1a or co-expressed hERG 1a/1b channel isoforms. Materials and Methods: Measurements of hERG current (IhERG) were made at 37°C from HEK-293 cells expressing either the hERG1a isoform or co-expressing hERG1a and 1b isoforms. A standard “square” waveform voltage protocol was used to elicit IhERG, and tail current measurements were used to construct concentration-response relations for each drug. Results: For fluoxetine, cisapride, and chloroquine, the observed potencies of inhibition of IhERGwere similar between hERG1 and 1a/1b expression conditions. Further experiments in which the hERG1b isoform was expressed alone also failed to show different potencies from hERG1a for these drugs. Fluoxetine was also tested at room temperature and showed similar potencies against hERG 1a and 1a/1b. EBA was more potent against hERG1a than hERG1a/1b with respective half maximal inhibitory concentration (IC50) values of 32 nM ( 95% confidence interval [CI] 24 nM–43 nM) and 185 nM (CI 114 nM–304 nM), a 5.8-fold difference. At ambient temperature, EBA was also more potent against hERG1a than 1a/1b, with a 2.4-fold difference in IC50. Conclusion: Comparison of these findings with prior planar patch-clamp data suggests that automated patch-clamp data on hERG1a/1b versus hERG 1a at ambient temperature cannot automatically be extrapolated to manual patch clamp at 37°C. The results with EBA highlight that, during hERG screening of novel drugs, there is a case for promising candidates to incorporate some measurements on hERG1a/1b as well as hERG1a channels.
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Adverse drug reactions at an addiction psychiatry center: A cross-sectional analysis p. 104
Siddharth Sarkar, Rakesh K Chadda, Anusha Thota, Naveen Kumar Dhagudu, Thota Prasad
DOI:10.4103/jpp.JPP_41_18  
Objective: To perform a cross sectional analysis of anticipated and unanticipated adverse drug reactions occurring at an addiction psychiatry center. Materials and Methods: This observational analysis presents data on the ADRs reported by the health-care professionals at a tertiary care public-funded treatment center. The types of ADRs encountered over a period of 12 months are presented along. Results: A total of 251 ADRs were encountered in patients with substance use disorders. Of them, 23% were unlabeled adverse reactions. At the center, tramadol was the most common medication implicated for ADR, followed by naltrexone and disulfiram. The most common adverse event reported was loss of appetite (n = 26). According to the system organ classification, gastrointestinal (18.7%) and psychiatric symptoms (18.7%) were the most common systems implicated. Conclusion: The current findings provide opportunities for sensitization of health-care professionals. This will help in promoting safer drug use in the field of addiction psychiatry.
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Tumor necrosis factor-alpha − 308 gene polymorphism in the association between gestational diabetes mellitus and chronic periodontitis in South Indian population p. 109
Dhayanand John Victor, Sangeetha Subramanian, Prakash Ponnudurai Samuel Gnana, Bob Jacob Joseph
DOI:10.4103/jpp.JPP_45_18  
Objective: To investigate if tumor necrosis factor-alpha (TNF-α) G308A polymorphism influences the association between generalized chronic periodontitis (GCP) and gestational diabetes mellitus (GDM) in South Indian population. Materials and Methods: Clinical parameters were recorded in 99 CP patients who were categorized into two groups. The control group consisted of 49 individuals without GDM. The test group included fifty GCP patients with GDM. Genomic deoxyribonucleic acid was extracted from all the participants. The locus − 308 of TNF-α has frequently been associated with CP and DM, and hence this locus has been chosen for the study. Genotyping was carried out using allele-specific-polymerase chain reaction, and the frequencies of genotype were analyzed between the groups. Results: The distribution of genotype and allele frequencies showed significant differences between the study groups. The frequency of GA genotype was significantly higher in CP patients with GDM compared to patients without GDM (P = 0.014). The frequency of A allele was also significantly higher in GDM patients (31%) than non-GDM patients (13%) with CP. Conclusion: TNF-α G308A polymorphism could be a risk factor for the association between GDM and CP in South Indian population.
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RESEARCH LETTER Top

Impact of educational intervention on the awareness of disposal of leftover/expired medicines among health care professionals p. 113
Manoj Goyal, Monika Bansal, Anurag Bajpai, Aboobecker Siddique, RK Srivastava
DOI:10.4103/jpp.JPP_44_18  
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CASE REPORT Top

Dapsone-Induced methemoglobinemia: Blue cures blue p. 117
Basil Jose, Josephine Valsa Jose, Mobin Paul
DOI:10.4103/jpp.JPP_16_18  
Dapsone, a sulfone group antibiotic, was traditionally used for the treatment of leprosy. It has potent anti-inflammatory and immunosuppressive properties. Hence later, its use has been expanded to conditions such as acne vulgaris, dermatitis herpetiformis, chronic immune thrombocytopenia, pemphigoid, malaria, and cutaneous leishmaniasis. Dapsone is less expensive and effective second-line treatment used in chronic immune thrombocytopenia (c ITP). It is metabolized in the liver by cytochrome P-450 enzymes to potent oxidants that are responsible for the adverse hematological complications like methemoglobinemia. We hereby report a case of dapsone-induced methemoglobinemia in an adult female patient used for the treatment of c ITP. She presented with hypoxia, fatigability, and improved subsequently on low-dose intravenous methylene blue. The patient was discharged without any complications. Initial assessment at Emergency services was suggestive of probable adverse drug reaction according to the WHO causality assessment scale and Naranjo algorithm. The preventability assessment was unpreventable according to Schumock and Thornton preventability assessment scale. A key to the diagnosis of methemoglobinemia is cyanosis with low-oxygen saturation and normal partial pressure of oxygen on arterial blood gas analysis. Treatment should be initiated immediately with IV methylene blue which acts by converting methemoglobin to normal hemoglobin, and thus, increasing the oxygen-carrying capacity of the red blood corpuscles. Dapsone-induced methemoglobinemia is rare but a life-threatening complication. Be cautious, when dapsone is used for the long-term treatment such as c ITP. Relevant pathophysiology and treatment principles are summarized in this case report to enhance awareness among physicians about this life-threatening adverse reaction to dapsone.
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