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Fulltext Digoxin toxicity: clinical and laboratory assessment

Ong HT, Ch'ng SL, Masduki A, Chandrasekharan N

Med J Malaysia, 1989 Dec;44(4):296-301.
PMID: 2520037

A prospective study to correlate clinical digoxin toxicity with serum digoxin levels was carried out in 67 patients of whom 24 were clinically toxic and 43 were asymptomatic. The patients were clinically diagnosed to be toxic based on typical cardiac arrhythmias (n = 11) or non-cardiac symptoms (n = 13). Blood samples were collected at least six hours after the last digoxin dose and the sera assayed for digoxin using a radioimmunoassay method. The mean serum digoxin level in the toxic group (x1 = 2.09 +/- 1.28 ng/ml) was significantly higher than in the non-toxic group (x2 = 1.20 +/- 0.75 ng/ml), p less than 0.01. All the non-toxic patients had serum digoxin levels below 3 ng/ml. However, there was a considerable overlap of serum digoxin levels between the two groups of patients. Serum level cannot be the sole criterion in diagnosing digoxin toxicity. Nevertheless, raised serum digoxin levels especially above 3 ng/ml, in the presence of suggestive clinical features is strongly suggestive of toxicity.

Matched MeSH terms: Digoxin/administration & dosage; Digoxin/adverse effects*; Digoxin/blood
Clinical judgement perplexed by initially undisclosed use of herbal medicine and unexpected cross-reactivity of immunoassay

Liu KT, Lee CW

Malays J Pathol, 2017 Aug;39(2):189-192.
PMID: 28866703

We report a case of symptomatic bradycardia caused by consumption of a Chinese herbal medicine which was initially undisclosed to the attending emergency physician. The scientific name of the herb is Panax japonicus. Electrocardiogram revealed sinus bradycardia. Laboratory tests were normal except for the detection of a high serum digoxin level. Further interrogation of the patient eventually disclosed ingestion of the herb which, however, did not contain any digoxin. Other active ingredients in the herb include various types of ginsenoside. These are digoxin-like substances that had caused the observed false-positive detection of digoxin by fluorescence polarization immunoassay due to cross-reactivity. Our case-report provides an important insight about a blind-spot in the field of laboratory medicine (clinical pathology), namely, the false positive detection of digoxin due to crossreactivity in the immunoassay when we come across digoxin-like substances in clinical scenarios, which has barely received attention in the medical literature. It also conveys a clear educational message that with full understanding of the laboratory methodology and its mechanistic rationale there are actually some tricks-of-the-trade that allow us to optimize the specificity of the biochemical tests and the treatment of digoxin-like substances overdose.

Matched MeSH terms: Digoxin/analysis; Digoxin/immunology
The inhibitory effects of mitragynine on P-glycoprotein in vitro

Rusli N, Amanah A, Kaur G, Adenan MI, Sulaiman SF, Wahab HA, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2019 04;392(4):481-496.
PMID: 30604191 DOI: 10.1007/s00210-018-01605-y

Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.

Matched MeSH terms: Digoxin/pharmacology
Detection of Epstein-Barr virus DNA in nasopharyngeal carcinoma using a non-radioactive digoxigenin-labelled probe

Permeen AM, Sam CK, Pathmanathan R, Prasad U, Wolf H

J Virol Methods, 1990 Mar;27(3):261-7.
PMID: 2157729

The presence of Epstein Barr virus (EBV) DNA in biopsies from the post-nasal space (PNS) of patients suspected of nasopharyngeal carcinoma (NPC) was detected by in situ cytohybridization with an EBV DNA probe labelled with the novel labelling compound digoxigenin. The digoxigenin probe was hybridised to cryostat sections of NPC biopsies and subsequently detected by an enzyme immunoassay procedure. It was found that in situ cytohybridization using the digoxigenin probe was much more rapid and sensitive (96 h compared to five weeks) than the current method of using 3H-labelled probe. Using the digoxigenin EBV probe, it was found that in all the eighteen NPC biopsies tested, EBV DNA was detected in malignant epithelial cells and infiltrating lymphocytes. EBV DNA was also detected in some normal epithelial cells in these NPC biopsies. EBV DNA was not detected in epithelial cells of non-malignant biopsies.

Matched MeSH terms: Digoxin/analogs & derivatives*
Fulltext Intrauterine management of fetal supraventricular tachycardia (SVT) with cardiac failure

Muniswaran G, Japaraj RP, Asri Ranga AR, Cheong HK

Med J Malaysia, 2015 Dec;70(6):371-2.
PMID: 26988216 MyJurnal

Fetal arrhythmias are not uncommon in pregnancy. The diagnosis can be established on routine ultrasound scan. Fetal supraventricular tachycardia (SVT) is the most common cause of fetal tachycardia. If left undiagnosed and untreated, these fetuses may develop cardiac failure, hydrops fetalis and eventually death. We report two fetuses diagnosed antenatally to have fetal SVT. Both fetuses were in cardiac failure and were successfully treated with maternal administration of antiarrhythmic medications. Digoxin, and in severe instances, a combination with flecanaide significantly improved fetal outcomes and prevented fetal mortality. The long term prognosis of such patients are good.

Matched MeSH terms: Digoxin
Fulltext Knowledge, perceptions, and attitudes toward complementary and alternative medicines among pharmacy students of a Malaysian public university

Jamshed SQ, Khan MU, Ahmad A, Elkalmi RM

J Pharm Bioallied Sci, 2016 3 10;8(1):34-8.
PMID: 26957866 DOI: 10.4103/0975-7406.171686

BACKGROUND: The use of complementary and alternative medicine (CAM) is consistently on the rise worldwide. Consumers often consider pharmacists as a major source of information about CAM products and their safety. Due to the limitation of data, it is worth exploring the knowledge, perceptions, and attitudes of pharmacy students toward CAM.
OBJECTIVE: The objective of this study was to explore the knowledge, perceptions, and attitudes of pharmacy students regarding the use of CAM in Malaysia.
MATERIALS AND METHODS: A cross-sectional study was conducted for 3 months among Bachelor of Pharmacy students in a public sector University of Malaysia. A pretested, self-administered questionnaire, comprised four sections, was used to collect the data from 440 participants. Descriptive analysis was used, and Chi-square test was used to test the association between dependent and independent variables.
RESULTS: Of 440 questionnaire distributed, 287 were returned giving a response rate of (65.2%). The results showed that 38.6% participants gave correct answers when asked about the use of herbal products with digoxin. Majority of the participants were knowledgeable about supplementary therapy (25.3%) while the lack of knowledge was mostly evident in traditional Chinese medicines (73.7%). Majority of the students were either neutral (49.5%) or disagreed that (42.8%) CAM use is unsafe. Females were more in disagreement to the statements than males (P = 0.007). Majority of students also agreed to use CAM therapies for their health and well-being (51.2%).
CONCLUSION: The study revealed that pharmacy students did not have adequate knowledge of CAM though their attitudes and perceptions were relatively positive.

Matched MeSH terms: Digoxin
Fulltext Evaluation of blood sampling times and indications for therapeutic drug monitoring services

Aishah Hamzah, Ab Fatah Ab Rahman

Malaysian Journal of Pharmaceutical Science, 2008;6(1):1-11.
MyJurnal

The appropriateness of sampling times and indications for monitoring of serum drug concentrations for the purpose of therapeutic drug monitoring (TDM) were evaluated at three hospitals on the east coast of Malaysia. Appropriateness criteria for indication and sampling were adapted from previously published criteria and with input from local TDM pharmacists. Six drugs were chosen, namely gentamicin, digoxin, carbamazepine, phenobarbital, phenytoin, and valproic acid. A total of 265 TDM requests were evaluated. Appropriateness of the indication for TDM ranged from 77.4% to 82%, while that for sampling ranged from 34.2% to 62.1%. There were no significant differences between the three hospitals in both categories of appropriateness. Among different drug groups, the percentage of appropriate indication was found to be highest with antiepileptic drugs. Antiepileptic drugs, however, had the lowest rate of appropriate sampling. Overall, findings from the three hospitals showed very encouraging results with almost 80% of the requests considered as appropriately indicated. However, the percentage of appropriateness of sampling was lower, and thus may require further investigation.

Matched MeSH terms: Digoxin
Fulltext Fetal supraventricular tachycardia--a case report

Soh EBS, Raman S, Chia PMK

Med J Malaysia, 1998 Sep;53(3):280-3.
PMID: 10968167

A gravid patient with fetal supraventricular tachycardia is presented. A review of this rare condition and the present recommended mode of therapy are discussed.

Matched MeSH terms: Digoxin/therapeutic use
Structure and function of proprotein convertase subtilisin/kexin type 9 (PCSK9) in atherosclerosis

Zhang L, Hussain Z, Ren Z

Curr Drug Targets, 2019 Feb 14.
PMID: 30767742 DOI: 10.2174/1389450120666190214141626

BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.
OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.
RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.
CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

Matched MeSH terms: Digoxin