scholarly journals A Systematic Review on Anti-tubercular Therapy Induced Hepatotoxicity

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Rashi Bahugunaa ◽  
Devesh Joshia ◽  
Yogesh Joshi
Keyword(s):  
Side Effects ◽  
Medical Staff ◽  
Cytochrome P450 Enzyme ◽  
Atp Production ◽  
Adequate Education ◽  
P450 Enzyme ◽  
Low Bmi ◽  
Anti Tubercular Therapy ◽  
Cytochrome P 450 ◽  
Primary Compound

Tuberculosis is the leading cause of major morbidities and mortalities around the globe. One in every three persons suffers from tubercular infection in their lifetime. Antitubercular therapy-induced hepatitis occurs due to toxicity from the primary compound, metabolite, or an immunologically mediated response. Risk factors associated with hepatotoxicity are age, sex, low BMI, hypoalbuminemia, alcohol consumption, HIV, hepatitis B, and C. There are 6 major pathways by which anti-TB drugs are involved in hepatotoxicity including hampering of intracellular calcium homeostasis, derangement of actin fibril assembly that occurs next to the canaliculus, the drug binds to the heme-containing cytochrome p-450 and forms enzyme-drug adduct and produces an immune response, The enzyme- drug addict when gets incorporated to vesicle acts as antigen for the production antibodies, some drugs also inhibit the ? oxidation and respiration and hence reduction in ATP production hence damaging cell and mitochondrial DNA, and some directly leads to apoptosis. Isoniazid is being metabolized to acetyl-isoniazid followed by hydrolysis to acetyl hydrazine via cytochrome P450 enzyme which produces toxic metabolites responsible for hepatotoxicity. Rifampicin activates the cytochrome enzyme and hence stimulates the production of harmful toxic materials leading to ATT-induced hepatotoxicity. It is the duty of the he pharmacist / medical staff has to provide the patient with adequate education about diseases and to inform them about their therapy regarding possible side effects and side effects. Pharmacists / medical staff must also train patients to comply with medication.

Use of antidepressants in a modern globalized society

2010 ◽  
Vol 7 (03) ◽  
pp. 162-168 ◽  
Author(s):  
T. Haslemo ◽  
L. Tanum
Keyword(s):  
Treatment Outcome ◽  
Genetic Factors ◽  
Enzyme System ◽  
Therapeutic Drug ◽  
Cytochrome P450 Enzyme ◽  
Relevant Factor ◽  
The World ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Cytochrome P 450

SummaryDepression is a highly prevalent condition throughout the world. Ethnicity is reported to influence treatment outcome with antidepressants in a number of ways, including both cultural and genetic factors. Non-genetic factors such as the type of diet, beliefs about depression and attitudes towards treatment with antidepressants are proposed to directly influence medication adherence and the rate of remission. Genetic factors are mainly expressed through inter-individual variance in drug metabolism and must be born in mind when antidepressants are prescribed in a multi-ethnic society. Recent advances in molecular biology have revealed substantial variance in the Cytochrome-P450 enzyme system, which is considered to be the most important and relevant factor for ethnic variance in the metabolism. This underscores the usefulness of therapeutic drug monitoring and individualization of treatment in clinical practice. This paper will briefly review factors related to ethnicity that may be of potential importance for treatment outcome and with a special emphasis on the ethnical diversity of cytochrome P-450 enzyme systems.

scholarly journals A Week of Oral Terbinafine Pulse Regimen Every Three Months to Treat all Dermatophyte Onychomycosis

2019 ◽  
Vol 5 (3) ◽  
pp. 82
Author(s):  
Anarosa B. Sprenger ◽  
Katia Sheylla Malta Purim ◽  
Flávia Sprenger ◽  
Flávio Queiroz-Telles
Keyword(s):  
Side Effects ◽  
Fungal Infections ◽  
Pulse Therapy ◽  
Pharmacokinetic Data ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Group 2 ◽  
Treat All ◽  
Long Pulse ◽  
Oral Terbinafine

Terbinafine has proved to treat numerous fungal infections, including onychomycosis, successfully. Due to its liver metabolization and dependency on the cytochrome P450 enzyme complex, undesirable drug interaction are highly probable. Additionally to drug interactions, the treatment is long, rising the chances of the appearance of side effects and abandonment. Pharmacokinetic data suggest that terbinafine maintains a fungicidal effect within the nail up to 30 weeks after its last administration, which has aroused the possibility of a pulse therapy to reduce the side effects while treating onychomycosis. This study’s goal was to evaluate the effectiveness of three different oral terbinafine regimens in treating onychomycosis due to dermatophytes. Sixty-three patients with onychomycosis were sorted by convenience in three different groups. Patients from group 1 received the conventional terbinafine dose (250 mg per day for 3 months). Group 2 received a monthly week-long pulse-therapy dose (500 mg per day for 7 days a month, for 4 months) and group 3 received a 500 mg/day dose for 7 days every 3 months, totaling four treatments. There were no statistical differences regarding the effectiveness or side effects between the groups. Conclusion: A quarterly terbinafine pulse regimen can be a possible alternative for treating onychomycosis caused by dermatophytes.

Polymorphisms in alcohol metabolizing genes ADH2 and ADH3 and susceptibility to pancreatitis in alcoholics

2017 ◽  
Vol 6 (03) ◽  
pp. 5297
Author(s):  
Vedangi Aaren* ◽  
Godi Sudhakar ◽  
Girinadh L.R.S.
Keyword(s):  
Frequency Distribution ◽  
Ethanol Metabolism ◽  
Alcoholic Pancreatitis ◽  
Cytochrome P450 Enzyme ◽  
Increased Risk ◽  
Significant Difference ◽  
Pcr Rflp ◽  
P450 Enzyme ◽  
Acute Alcoholic Pancreatitis ◽  
Acute And Chronic Pancreatitis

In both developed and developing countries, overuse of alcohol is a considered as the major cause of acute and chronic pancreatitis. Prolonged overconsumption of alcohol for 5–10 years typically precedes the initial attack of acute alcoholic pancreatitis. It is observed that only a minority (around 5%) of alcoholics develop pancreatitis. It is now established that the pancreas has the capacity to metabolize ethanol. Previous studies have shown that there are two major pathways of ethanol metabolism, oxidative and non-oxidative. Oxidative ethanol metabolism involves the conversion of ethanol to acetaldehyde, a reaction that is catalysed by aldehyde dehydrogenase (ADH) with contributions from cytochrome P450 enzyme (CYP2E1) and possibly also catalase. Genetic factors regulating alcohol metabolism could predispose in developing alcoholic pancreatitis (AP). We investigated the association of polymorphisms in ADH enzymes with the alcoholic pancreatitis in North coastal Andhra Pradesh. Patients with alcoholic pancreatitis (AP; n = 100), alcoholic controls (AC; n = 100), and healthy controls (HC; n = 100) were included in the study. Blood samples were collected from the subjects in EDTA coated vials. DNA was extracted and genotyping for ADH2 and ADH3 was done by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism). The products were analysed by gel electrophoresis. The frequency distribution of ADH3*1/*1 genotype was significantly higher in AP group (54%) compared with AC (35%), and HC (42%), and was found to be associated with increased risk of alcoholic pancreatitis. There was no statistically significant difference between the frequency distribution of ADH3*1/*1, ADH3*1/*2, and ADH3*2/*2 genotypes between AC and HC. There was no statistically significant difference between the frequency distribution of ADH2*1/*1, ADH2*1/*2, and ADH2*2/*2 genotypes in AP compared with AC and HC. This study shows that carriers of ADH3*1/*1 individuals consuming alcohol are at higher risk for alcoholic pancreatitis than those with other genotypes such as ADH3*1/*2 and ADH3*2/*2. 

scholarly journals Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

2021 ◽  
Author(s):  
E. Heinonen ◽  
M. Blennow ◽  
M. Blomdahl-Wetterholm ◽  
M. Hovstadius ◽  
J. Nasiell ◽  
...  
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Plasma Concentrations ◽  
Relative Difference ◽  
Interindividual Variation ◽  
Therapeutic Drug ◽  
Cytochrome P450 Enzyme ◽  
Second Trimester ◽  
P450 Enzyme ◽  
Placental Passage

Abstract Purpose Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. Method Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. Results Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. Conclusion Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. Trial registration The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

The role of cytochrome P450 enzyme genetic variants in cannabis hyperemesis syndrome—A case report

2021 ◽  
Author(s):  
Maxim Kuzin ◽  
Franziskos Xepapadakos ◽  
Isabel Scharrer ◽  
Marc Augsburger ◽  
Chin‐Bin Eap ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Genetic Variants ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Cannabis Hyperemesis Syndrome

scholarly journals Assessment of the Aromatase Inhibitory Activity of Ma-Huang-Tang (MHT) and Its Active Compounds

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Dong Ho Jung ◽  
Joo Tae Hwang ◽  
Bo-Jeong Pyun ◽  
Song Yi Yu ◽  
Byoung Seob Ko
Keyword(s):  
Herbal Medicines ◽  
Inhibitory Effect ◽  
Aromatase Activity ◽  
Cytochrome P450 Enzyme ◽  
Active Components ◽  
Glycyrrhizae Radix ◽  
Potent Inhibition ◽  
P450 Enzyme ◽  
Medicine Prescription ◽  
Ma Huang

Aromatase, a cytochrome P450 enzyme that converts androgens into estrogens, is an important drug target for hormone-dependent diseases. The purpose of this study was to elucidate the aromatase inhibitory effects of Ma-Huang-Tang (MHT), a traditional Korean herbal medicine prescription, and to identify its active ingredients. In this study, the inhibitory effect of MHT on aromatase activity was observed using dibenzylfluorescein (DBF) and KGN cells, and the dose-dependent effect of MHT was verified (IC50 values of 251 μg/mL and 246 μg/mL as determined by the two methods, respectively). Furthermore, among the six herbal medicines that constitute MHT, Ephedrae Herba, Cinnamomi Ramulus, and Glycyrrhizae Radix et Rhizoma showed the most potent inhibition of aromatase activity. Furthermore, upon identification of the active MHT compounds, three markers from Glycyrrhizae Radix et Rhizoma, liquiritin (5), liquiritin apioside (6), and liquiritigenin (7), were verified (IC50 values of 530 μM, 508 μM, and 1.611 mM and 499 μM, 522 μM, and 1.41 mM as determined by the two methods, respectively). In addition, their contents were confirmed to be 15.58, 19.80, and 2.22 mg/g, respectively, by HPLC/DAD analysis. These results indicate that the aromatase inhibitory effect of MHT results from the synergistic action of its active components and that MHT has potential as a preventive agent against aromatase activity.

Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male ruminants

2003 ◽  
Vol 77 (10) ◽  
pp. 555-560 ◽  
Author(s):  
Miroslav Machala ◽  
Pavel Soucek ◽  
Jir� Neca ◽  
Robert Ulrich ◽  
Jir� Lamka ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Species Comparisons ◽  
Hepatic Cytochrome

scholarly journals Evidence that high variation in antral follicle count during follicular waves is linked to alterations in ovarian androgen production in cattle

Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 713-720 ◽  
Author(s):  
F Mossa ◽  
F Jimenez-Krassel ◽  
J K Folger ◽  
J L H Ireland ◽  
G W Smith ◽  
...  
Keyword(s):  
Serum Testosterone ◽  
Antral Follicle ◽  
Antral Follicle Count ◽  
Cytochrome P450 Enzyme ◽  
Follicular Waves ◽  
Androgen Synthesis ◽  
Thecal Cells ◽  
P450 Enzyme ◽  
Ovulatory Follicles ◽  
And Function

Androgens have an important role in ovarian follicular growth and function, but circulating androgen concentrations are also associated with ovarian dysfunction, cardiovascular disease, and metabolic disorders in women. The extent and causes of the variation in androgen production in individuals, however, are unknown. Because thecal cells of follicles synthesize androstenedione and testosterone, variation in production of these androgens is hypothesized to be directly related to the inherently high variation in number of healthy growing follicles in ovaries of individuals. To test this hypothesis, we determined whether thecal CYP17A1 mRNA (codes for a cytochrome P450 enzyme involved in androgen synthesis), LH-induced thecal androstenedione production, androstenedione concentrations in follicular fluid, and circulating testosterone concentrations were lower in cattle with relatively low versus high number of follicles growing during follicular waves and whether ovariectomy reduced serum testosterone concentrations. Results demonstrated that cattle with a low follicle number had lower (P<0.05) abundance of CYP17A1 mRNA in thecal cells, reduced (P<0.01) capacity of thecal cells to produce androstenedione in response to LH, lower (P<0.01) androstenedione concentrations in ovulatory follicles, and lower (P<0.02) circulating testosterone concentrations during estrous cycles compared with animals with high follicle number. Also, serum testosterone in cattle with low or high follicle number was reduced by 63 and 70%, respectively, following ovariectomy. In conclusion, circulating androgen concentrations are lower in cattle with low versus high number of follicles growing during follicular waves, possibly because of a reduced responsiveness of thecal cells to LH.

scholarly journals Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients

2018 ◽  
Vol 28 (1) ◽  
pp. 56-62
Author(s):  
Cahit Kural ◽  
Arzu Kaya Kocdogan ◽  
Gulcin Güler Şimşek ◽  
Serpil Oğuztüzün ◽  
Pınar Kaygın ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Brain Tissue ◽  
Pituitary Adenomas ◽  
Normal Brain ◽  
Cytochrome P450 Enzyme ◽  
Intracranial Tumors ◽  
Glutathione S Transferase ◽  
Normal Brain Tissue ◽  
Tissue Samples ◽  
P450 Enzyme

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP­1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

Drug Interactions of Macrolides: Emphasis on Dirithromycin

1997 ◽  
Vol 31 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Vish S Watkins ◽  
Ron E Polk ◽  
Jennifer L Stotka
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Ethinyl Estradiol ◽  
Enzyme System ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
Kidney Transplant Recipients ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Clinically Significant

Objective To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides. Data Sources A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company. Data Synthesis Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug–drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug–drug interactions. Conclusions Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin.

Sign in / Sign up

Export Citation Format

Share Document