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Fulltext Erythromycin induced torsade de pointes in a methadone maintenance patient: case report

Noor Zurani Md Haris Robson, Mohamad Hussain Habil

ASEAN Journal of Psychiatry, 2010;11(1):103-107.
MyJurnal

Objective: This case report highlights the risk of Torsade de Pointes (TdP), a life threatening cardiac arrhythmia in a heroin dependent patient receiving methadone substitution therapy who was prescribed erythromycin for upper respiratory tract infection. Method: We report a case of a 35-year-old Malay man on methadone maintenance treatment who developed TdP possibly due to drug interaction between methadone and erythromycin. Results: The
patient reported feeling unwell, chest pain and feeling dizzy after consuming 2 doses of erythromycin. ECG monitoring showed prolonged rate-corrected QT interval leading to TdP. The patient was admitted to the ward where the cardiac arrhythmia ceased following methadone discontinuation. This cardiac arrhythmia was most likely due to drug interaction between methadone and erythromycin (an enzyme inhibitor) which led to an increase in methadone concentration and potentiated the adverse effects. Conclusion: As methadone is a beneficial treatment for heroin dependent patients, the risk of cardiac arrhythmia is of great concern. To avoid complications of drug interaction, patients on methadone therapy should be advised to seek medical assessment before taking other drugs. As TdP is life threatening, it is thus important that physicians and psychiatrists involved in the treatment of
heroin dependent patients on methadone substitution therapy be made aware of this risk.

Matched MeSH terms: Drug Interactions
Influence of sympathetic and AT-receptor blockade on angiotensin II and adrenergic agonist-induced renal vasoconstrictions in spontaneously hypertensive rats

Abdulla MH, Sattar MA, Khan MA, Abdullah NA, Johns EJ

Acta Physiol (Oxf), 2009 Mar;195(3):397-404.
PMID: 19183357 DOI: 10.1111/j.1748-1716.2008.01895.x

This study investigated the influence of angiotensin II (Ang II) receptor and adrenergic blockade on the renal vasoconstrictions caused by Ang II and adrenergic agonists in spontaneously hypertensive rats (SHR).

Matched MeSH terms: Drug Interactions
iMSEA: A Novel Metabolite Set Enrichment Analysis Strategy to Decipher Drug Interactions

Wang Y, Liu X, Dong L, Cheng KK, Lin C, Wang X, et al.

Anal Chem, 2023 Apr 18;95(15):6203-6211.
PMID: 37023366 DOI: 10.1021/acs.analchem.2c04603

Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.

Matched MeSH terms: Drug Interactions
Fulltext Role of bilastine in the management of allergic rhinitis and urticaria: an Asia-Pacific consensus statement

Mösges R, Lee DL, Abong J, Siasoco B, Chow SK, Leong JL, et al.

Asia Pac Allergy, 2016 Jan;6(1):56-66.
PMID: 26844221 DOI: 10.5415/apallergy.2016.6.1.56

The prevalence of allergic diseases is increasing globally, most particularly in middle- to low-income countries. This article examines the burden of allergic rhinitis and chronic urticaria in the Asia-Pacific region, unmet clinical needs, and the potential role of bilastine in the management of these conditions. An International Advisory Group meeting was convened in association with the Asian Pacific Society of Respirology Annual Congress in November 2014, followed by a literature review, and consensus-based outcomes from the meeting and literature review are described. Regional estimates of the prevalence of allergic rhinitis range from 10% to 50%, while little is known regarding the burden of urticaria in the Asia-Pacific region. A survey of allergy patients in the region identified fast, complete, and long-lasting symptom relief as the medication attributes most important to patients. International treatment guidelines for allergic rhinitis and urticaria advocate the first-line use of second-generation, no-sedating H1-antihistamines, such as bilastine, over their first-generation counterparts and a range of these agents are available to Asia-Pacific patients. The newer agents possess many of the properties of an "ideal" antihistamine (once daily administration, rapid and complete symptom relief, limited potential for drug-drug interactions, minimal side effects). The burgeoning prevalence of allergic diseases in the Asia-Pacific region and the uncontrolled symptoms that these patients experience demand a new antihistamine that offers the highest number of positive features according to the international guidelines.

Matched MeSH terms: Drug Interactions
Fulltext Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice

Lim AY, Segarra I, Chakravarthi S, Akram S, Judson JP

BMC Pharmacol., 2010;10:14.
PMID: 20950441 DOI: 10.1186/1471-2210-10-14

BACKGROUND: Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration.
RESULTS: Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs.
CONCLUSIONS: Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.

Matched MeSH terms: Drug Interactions
Fulltext Hypertensive bipolar: chronic lithium toxicity in patients taking ACE inhibitor

Masiran R, Abdul Aziz MF

BMJ Case Rep, 2017 Aug 28;2017.
PMID: 28847993 DOI: 10.1136/bcr-2017-220631

A patient with bipolar I disorder has been treated with lithium and haloperidol for the last 20 years and received an ACE inhibitor for his hypertension since 9 years ago. Despite regular clinic follow-ups and blood monitoring, he recently developed tremors and delirium. On hospital admission, serum level of lithium was far above toxic level. Mental state examination revealed an anxious and disorientated man with irrelevant speech. Immediate discontinuation of lithium resulted in slow reduction of serum lithium levels and gradual resolution of tremor but his delirium persisted for 2 weeks. His condition took a turn for the worse when he developed acute renal failure and arm abscess. We discussed about lithium toxicity and the vulnerability factors which have induced delirium and renal failure in this patient.

Matched MeSH terms: Drug Interactions
Fulltext Schizophrenia and anaesthesia

Constance LSL, Lansing MG, Khor FK, Muniandy RK

BMJ Case Rep, 2017 Nov 23;2017.
PMID: 29170175 DOI: 10.1136/bcr-2017-221659

Administering anaesthesia for elderly patients with chronic schizophrenia has always been a great challenge to anaesthetists. These patients will usually be on multiple antipsychotic drugs for many years and may lead to delayed awakening, cardiovascular instability, arrhythmias and sudden cardiac death during general anaesthesia. This case report is about the perioperative anaesthetic management of an elderly schizophrenic patient undergoing removal of femur implant. This article will explore important drug interactions and available options for a successful anaesthesia.

Matched MeSH terms: Drug Interactions
Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats

Yusoff NHM, Mansor SM, Müller CP, Hassan Z

Behav Brain Res, 2018 06 01;345:65-71.
PMID: 29499286 DOI: 10.1016/j.bbr.2018.02.039

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABAB receptor.

Matched MeSH terms: Drug Interactions
Fulltext Bacteriostatic antimicrobial combination: antagonistic interaction between epsilon-viniferin and vancomycin against methicillin-resistant Staphylococcus aureus

Basri DF, Xian LW, Abdul Shukor NI, Latip J

Biomed Res Int, 2014;2014:461756.
PMID: 24783205 DOI: 10.1155/2014/461756

Stilbenoids have been considered as an alternative phytotherapeutic treatment against methicillin-resistant Staphylococcus aureus (MRSA) infection. The combined effect of ε-viniferin and johorenol A with the standard antibiotics, vancomycin and linezolid, was assessed against MRSA ATCC 33591 and HUKM clinical isolate. The minimum inhibitory concentration (MIC) value of the individual tested compounds and the fractional inhibitory concentration index (FICI) value of the combined agents were, respectively, determined using microbroth dilution test and microdilution checkerboard (MDC) method. Only synergistic outcome from checkerboard test will be substantiated for its rate of bacterial killing using time-kill assay. The MIC value of ε -viniferin against ATCC 33591 and johorenol A against both strains was 0.05 mg/mL whereas HUKM strain was susceptible to 0.1 mg/mL of ε-viniferin. MDC study showed that only combination between ε-viniferin and vancomycin was synergistic against ATCC 33591 (FICI 0.25) and HUKM (FICI 0.19). All the other combinations (ε-viniferin-linezolid, johorenol A-vancomycin, and johorenol A-linezolid) were either indifferent or additive against both strains. However, despite the FICI value showing synergistic effect for ε-viniferin-vancomycin, TKA analysis displayed antagonistic interaction with bacteriostatic action against both strains. As conclusion, ε-viniferin can be considered as a bacteriostatic stilbenoid as it antagonized the bactericidal activity of vancomycin. These findings therefore disputed previous report that ε-viniferin acted in synergism with vancomycin but revealed that it targets similar site in close proximity to vancomycin's action, possibly at the bacterial membrane protein. Hence, this combination has a huge potential to be further studied and developed as an alternative treatment in combating MRSA in future.

Matched MeSH terms: Drug Interactions
Effects of iridoids on lipoxygenase and hyaluronidase activities and their activation by beta-glucosidase in the presence of amino acids

Ling SK, Tanaka T, Kouno I

Biol Pharm Bull, 2003 Mar;26(3):352-6.
PMID: 12612446

Enzyme inhibitory activities of 14 iridoids previously obtained from two Malaysian medicinal plants, Saprosma scortechinii and Rothmannia macrophylla, were evaluated in vitro using soybean lipoxygenase and bovine testis hyaluronidase. Most of the iridoids, including asperulosidic acid, paederosidic acid, and an epimeric mixture of gardenogenins A and B, did not show any effect on the enzyme activities, except for the bis-iridoids, which inhibited the lipoxygenase activity with their IC(50) values of approximately 1.3 times that of a known inhibitor, fisetin. Structural modification of asperulosidic acid and paederosidic acid through enzymatic hydrolysis by beta-glucosidase resulted in their inhibition towards the enzyme activities, and these activities were enhanced by the presence of some amino acids (lysine, leucine or glutamic acid) or ammonium acetate. Mixtures of gardenogenins A and B; isomers of non-glucosidic iridoids, incubated with amino acid or ammonium acetate did not show any inhibitory effect on the enzyme activities during the 6 h incubation period, except for lysine where spontaneous reaction between the iridoids and amino acid resulted in the inhibition of lipoxygenase activity. The results from these biomimetic reactions suggested that the iridoid aglycons and the intermediates formed by these reactive species could inhibit the enzyme activities, and thus substantiate previous reports that the formation of iridoidal aglycons is a prerequisite for the iridoid glycosides to demonstrate some of the biological activities. In addition, the results also indicated that it is worthwhile to further explore these intermediates as potential anti-inflammatory agents.

Matched MeSH terms: Drug Interactions
Cytochrome P450 2C9-natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data

Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, et al.

Biopharm Drug Dispos, 2018 Apr;39(4):205-217.
PMID: 29488228 DOI: 10.1002/bdd.2127

Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.

Matched MeSH terms: Drug Interactions
Evidence of an interaction between nifedipine and nafcillin in humans

Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC

Br J Clin Pharmacol, 2003 Jun;55(6):588-90.
PMID: 12814453

AIMS: Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to induce the metabolism of cyclosporin and warfarin, which are known substrates of cytochrome P-450 (CYP). However, there has not been any report to date on its possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4.
METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.
RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).
CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.

Matched MeSH terms: Drug Interactions
The effect of various drugs on the glucuronidation of zidovudine (azidothymidine; AZT) by human liver microsomes

Sim SM, Back DJ, Breckenridge AM

Br J Clin Pharmacol, 1991 Jul;32(1):17-21.
PMID: 1909542

1. Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the drug of proven efficacy available for the treatment of patients with AIDS or ARC. It is eliminated mainly by hepatic glucuronidation. Therefore, interference with this metabolic pathway may lead to enhancement of AZT effect or to increased toxicity of the drug. We have examined the effect of a number of drugs which themselves undergo glucuronidation on AZT conjugation by human liver microsomes in vitro. 2. AZT glucuronidation followed Michaelis-Menten kinetics. The apparent Km and Vmax values (mean +/- s.d., n = 5), were 2.60 +/- 0.52 mM and 68.0 +/- 23.4 nmol h-1 mg-1, respectively, as determined from Eadie-Hofstee plots. 3. Dideoxyinosine, sulphanilamide and paracetamol were essentially non-inhibitory at concentrations up to 10 mM (4 times the concentration of AZT in the incubation). The most marked inhibitory effects were seen with indomethacin, naproxen, chloramphenicol, probenecid and ethinyloestradiol, with enzyme activity decreased by 97.7, 94.9, 88.7, 83.4% and 79.0%, respectively, at a concentration of 10 mM. Other compounds producing some inhibition of AZT conjugation were oxazepam, salicylic acid and acetylsalicylic acid. 4. Further studies are necessary to characterise the inhibition observed but the method described enables a screen of potentially important drug interactions to be carried out.

Matched MeSH terms: Drug Interactions
Toxicity of single and combinations of lead and cadmium to the cyanobacteria Anabaena flos-aquae

Heng LY, Jusoh K, Ling CH, Idris M

Bull Environ Contam Toxicol, 2004 Feb;72(2):373-9.
PMID: 15106775
Matched MeSH terms: Drug Interactions
Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice

Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.

Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
PMID: 27495788 DOI: 10.1007/s00280-016-3120-9

PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.
METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.
RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p

Matched MeSH terms: Drug Interactions
A comprehensive review on potential drug-drug interactions of proton pump inhibitors with antidiabetic drugs metformin and DPP-4 inhibitors

Tasnim J, Hashim NM, Han HC

Cell Biochem Funct, 2024 Mar;42(2):e3967.
PMID: 38480622 DOI: 10.1002/cbf.3967

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP-4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP-4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP-4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP-4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.

Matched MeSH terms: Drug Interactions
siRNA-mediated inhibition of survivin gene enhances the anti-cancer effect of etoposide in U-937 acute myeloid leukemia cells

Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Ismail P, et al.

Cell Mol Biol (Noisy-le-grand), 2016 May 30;62(6):44-9.
PMID: 27262801

Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and siRNA-mediated silencing of survivin on U-937 acute myeloid leukemia cells. The AML cells were transfected with survivin specific siRNA and gene knockdown was confirmed by quantitative real time PCR and western blotting. Subsequently, U-937 cells were assessed for response to etoposide treatment and apoptosis rate was measured with flowcytometery. The cytotoxic effects in siRNA-etoposide group were measured and compared to etoposide single therapy group. Survivin siRNA effectively knocked down the mRNA and protein levels of survivin, which led to lower cell proliferation and enhanced apoptosis. Furthermore, combined treatment of etoposide and survivin siRNA synergistically increased the cell toxic effects of etoposide and its ability to induce apoptosis.

Matched MeSH terms: Drug Interactions
Effect of acetylcholine and morphine on bronchial smooth muscle contraction and its modulation by steroid hormones

Nabishah BM, Morat PB, Khalid BA, Kadir BA

Clin Exp Pharmacol Physiol, 1990 Dec;17(12):841-7.
PMID: 2092952

1. The effects of corticosteroid pretreatment on acetylcholine (ACH)-induced contraction of bronchial smooth muscle (BSM) were studied. 2. ACH dose-response curves for dexamethasone (DM)- and corticosterone (B)-treated but not deoxycorticosterone (DOC)-treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH. 3. Morphine enhanced BSM contraction in response to ACH by 20%. DM suppressed this enhancement. 4. These findings correlated well with the reduction of muscarinic receptor numbers in BSM by glucocorticoids in our previous study. In addition, glucocorticoids reduced the sensitivity of BSM to opioids.

Matched MeSH terms: Drug Interactions
Herbal medicines in Malaysia

Ang HH

Clin. Pharmacol. Ther., 2005 May;77(5):451.
PMID: 15900291
Matched MeSH terms: Herb-Drug Interactions
Potential drug-herb interaction with antiplatelet/anticoagulant drugs

Saw JT, Bahari MB, Ang HH, Lim YH

Complement Ther Clin Pract, 2006 Nov;12(4):236-41.
PMID: 17030294

This is a cross-sectional survey evaluating the use of herbal medicines in medical wards patients that may interfere with the effect of antiplatelet or anticoagulant therapy. Among the 250 patients participated, 42.4% (n=106) were taking herbs with 76 patients (71.7%) using herbs for the past 12 months. Overall, almost 31% (n=23, N=76) of patients were taking one or more of the specified herbal medicines [ginseng (Panax ginseng), garlic (Allium sativum), ginkgo (Gingko biloba) thought to interact with antiplatelet or anticoagulant therapy. The study showed that 21% (n=16, N=76) of patients co-ingested specified herbs with antiplatelet or anticoagulant therapy, of which half of them were at risk of potential drug-herb interactions. A large proportion of respondents involved in potential drug-herb interaction were elderly people (62.5%, n=5). However, more than 90% of herbal users did not disclose the use of herbal medicine to their health professionals. It is thus prudent for all care givers to be aware of the possibility of drug-herb interaction and inquire about herbal use from patients.

Matched MeSH terms: Herb-Drug Interactions*

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