Clinical Drug Interactions: A Holistic View

Pharmacokinetic (PK) drug-drug interactions (DDIs) give rise to adverse events and/or reduced efficacy. Comprehensive, systematic and mechanistic approaches have been applied in the evaluation, propagation and management of the interaction potential of a new drug during its development and clinical use. However, the role of drug metabolite(s) in DDIs was not extensively investigated. Recently, regulatory bodies have proposed that metabolites at ≥25% of the parent drug's area under the time-concentration curve (AUC) and/or >10% of the total drug-related exposure should be investigated in vitro for DDI potential. This review aimed to identify the drugs and their metabolites meeting the official guidance's criteria for DDI studies, and to assess whether the eligible drugs caused significant clinical PK DDIs and furthermore whether the metabolites contributed to the observed PK DDIs. Eighty seven drugs were eligible and nearly 45% (39/87) drugs were not reported with clinical PK DDIs. About 78% (68/87) drugs demonstrated inhibitory and/or inducible effects on drug-metabolizing enzymes and/or drug transporters; while the remaining 19 (22%) parent drugs showed no such effects. For 8 drugs (~9%), their metabolites were able to inhibit and/or induce the drug-metabolizing enzymes and drug transporters. Three drugmetabolite pairs were found to be the perpetrators of the complex PK DDIs. Our retrospective analysis suggested that the PK DDI risks caused by metabolites alone might not be high, which is somewhat different from the conclusions from some other studies on this topic. However, circulating drugs often work as perpetrators of PK DDIs suggesting a need for more efforts to characterize the roles of their metabolites. Our study should be of value in stimulating discussions among the scientific community on this important topic.

Background: Self-medication with over-the-counter (OTC) medications is common among medical students. It is influenced by many factors, such as age, sex, income, self-care orientation, and medical knowledge. A high level of education and professional status are predictive factors for self-medication. Unfortunately, especially in developing countries, professional health care is relatively expensive and in some cases not readily available making self-medication an obvious choice of healthcare service. Furthermore, it has been noted that purchase of drugs that can only be purchased with a doctor's prescription in developed countries are OTC in developing countries. Students are expected to have proper knowledge, attitude, and practice (KAP) towards OTC medications and subsequent adverse drug reactions (ADRs). Objective: This study aimed to assess the KAP of OTC medication use and related factors among medical students, Uofk 2022. Methods: A cross-sectional study was conducted. Data were collected using a self-administered questionnaire from 377 students from year 1 to year 6 University of Khartoum, Faculty of Medicine.Then the data was analyzed using Statistical Package for Social Sciences (SPSS) version 24. Chi-square analysis was conducted and multivariable logistic regression analysis was used to determine the association between KAP and OTC use and its related adverse effects. Result: A total of 393 students participated in the study. The majority of the respondents (75.2%) reported that they practice self-medication. Fever & headache (76%), cough & common cold (48.5%), and abdominal cramps (45.7%)) were the most common conditions for which the students go for self-medication while analgesics (85.2%) followed by antispasmodics (72.4%) were the most commonly used classes of drugs. Minor illnesses (55.9%) and a desire for quick relief 171 (25%) were the main reasons for the self-medication practice with OTC medications. Conclusion: Self-medication is widely practiced among medical students. Significant problems and malpractices were identified, such as sharing of OTC medications, the use of expired medicines, storage of OTC medications, and not reading expiry dates. Table 1: Knowledge of the Study Participants Towards OTC Medication Use; N=393 Knowledge About OTC drugs: - Count Column Valid % All OTC (over the counter) drugs are safe and effective Yes 183 46.7%

In recent years, the non-medical use of prescription drugs (without a doctor's prescription) has increased dramatically. Less attention has been paid to the intentional misuse of over-the-counter (OTC) medications. Misuse of OTC medications has negative health consequences similar to those of illicit drugs, including psychosis, tachycardia, seizures and agitation. When mixed with alcohol or other drugs, these medications can also be dangerous: OTC-related emergency room visits increased 70% from 2004 to 2008. This study examined the intentional misuse of OTC medications, the non-medical use of prescription drugs, the use of alcohol and illicit drugs, and psychological factors in two samples of young adults (ages 18-25) from different areas of the United States (Total N = 1,197). Overall, 18.6% of the Colorado sample and 13.0% of the Virginia sample reported lifetime misuse of an OTC medication. Participants who reported misusing OTC medications were also significantly more likely to report using marijuana, ecstasy, cocaine, and non-medical use of prescription analgesics, stimulants, anxiolytics, and sedatives. Participants who reported misusing OTC medications were more than twice as likely to report hazardous alcohol use, relative to individuals who denied misusing OTC medications. Individuals who had misused OTC medications scored significantly higher in sensation seeking and hopelessness and reported more symptoms of depression, anxiety, and somatic distress, relative to those who denied OTC misuse. Results suggest that a considerable minority of young adults are jeopardizing their health with the misuse of OTC medications as part of a pattern of polysubstance use.

Background: While there are benefits for over-the-counter medication (OTC) use, there are serious risks associated with OTC usage. These include self-misdiagnosis, possible delay in receiving needed therapy, use of suboptimal therapy, and increased resistance to antimicrobial agents. The patterns of (OTC) usage among adolescents remains largely understudied. The objectives of this study are: (1) to determine the profile of OTC use among adolescents from the United Arab Emirates (UAE); and (2) to determine the biological or physical, psychological or behavioral, and social predictors of OTC use among the UAE adolescent population. Methods: In a cross-sectional study, we collected data on the prevalence of OTC use for a sample of 6,363 adolescents aged 13 to 20 years. We also collected demographic, socioeconomic, residential, and behavioral data. Analysis consisted of descriptive statistics, and bivariate and multivariate analyses. Logistic regression modelling was employed to examine predictors of over-the-counter medication use. Results: Overall, 51% of participants in this study reported OTC use. The most common form of OTC used was acetaminophen. Significant predictors of OTC use include nationality (UAE, GCC, Arab/Middle East, Arab/Africa, Western, Other), needed health care but did not receive it, sex (female), age (15–18 years), any medical diagnosis, unconventional drug use, spending more than 5 hours using TV and computer daily, and using prescription medicine. Conclusions: Considering the high prevalence of OTC use among adolescents from the UAE, public health policies and strategies that promote appropriate use of OTC in this population are needed.

Healthcare access and delivery faces significant global and local challenges. This article aimed to explore the public's use of pharmacy services and aimed to obtain 200 completed surveys across eight districts of Bristol, UK, from non-registered pharmacy premises. Respondents reported as follows: 1) ability to order a repeat prescription (79.47%), 2) ability to collect a repeat prescription (72.63%), 3) ability to collect an acute prescription (66.84%), ability to purchase over the counter (OTC) medicines (59.79%), 4) followed by asking for specific advice on prescription medicines (48.42%), and 5) minor ailments (44.15%). Respondents had used the pharmacy at least once for collecting a repeat prescription for a routine medication (59.47%) or acute prescription (55.79%) and for buying OTC medicines (47.89%). Majority of respondents never approached a community pharmacist to specifically ask advice on medicines (51.32%). Participants had not ever approached a community pharmacist for minor ailment/health advice (71.58%).

Healthcare access and delivery faces significant global and local challenges. This article aimed to explore the public's use of pharmacy services and aimed to obtain 200 completed surveys across eight districts of Bristol, UK, from non-registered pharmacy premises. Respondents reported as follows: 1) ability to order a repeat prescription (79.47%), 2) ability to collect a repeat prescription (72.63%), 3) ability to collect an acute prescription (66.84%), ability to purchase over the counter (OTC) medicines (59.79%), 4) followed by asking for specific advice on prescription medicines (48.42%), and 5) minor ailments (44.15%). Respondents had used the pharmacy at least once for collecting a repeat prescription for a routine medication (59.47%) or acute prescription (55.79%) and for buying OTC medicines (47.89%). Majority of respondents never approached a community pharmacist to specifically ask advice on medicines (51.32%). Participants had not ever approached a community pharmacist for minor ailment/health advice (71.58%).

To investigate self-reported beliefs and perceived sensitivity to medicines and their effects in relation to self-reported use of medicines and herbal remedies. A survey sent to 13,931 randomly selected Swedish adults included the Beliefs about Medicines Questionnaire-General (BMQ-General) Questionnaire and the Perceived Sensitivity to Medicines Scale (PSM). The survey also asked about individuals' use of prescribed and over-the-counter (OTC) medicines and herbal remedies in the past month. We examined all associations between scores on the BMQ-General subscales and PSM in relation to the use of medicines and herbal remedies, using analysis of covariance adjusted for potential confounders. Among 7099 respondents, those using herbal remedies exclusively believed strongly that prescription and OTC medicines are harmful and overprescribed. Respondents using prescription and OTC medicines reported more positive beliefs [coefficient 0.67 (95% CI 0.47-0.87) and 0.70 (95% CI 0.51-0.90)] on the benefits of medicines compared with those using herbal remedies [-0.18 (95% CI -0.57-0.20)]. Perceived sensitivity to medicines was higher among those using herbal remedies only [1.25 (95% CI 0.46-2.03)] compared with those using no medicines (reference 0) or prescription [-0.44 (95% CI -0.84 to -0.05)] or OTC [-0.27 (95% CI -0.66-0.12)] medicines alone. Respondents using prescription and/or OTC medicines reported stronger positive beliefs about the benefits of medicines in general, supporting the hypothesis that beliefs influence medicine use. Therefore, addressing beliefs and concerns about medicines during patient counselling may influence medicine use, particularly regarding unintentional non-adherence.

Although overshadowed by the prescription drug market, the over‐the‐counter (OTC) drug market should not be ignored. In 2003, sales in the United States, the five major European markets (France, Germany, Italy, Spain, and the United Kingdom), and Japan exceeded $40 billion (at retail prices), and the market has strong prospects for the future. Governments and other payers are increasingly looking to OTC drugs as a means of reducing their burgeoning expenditures on prescription medicines. The potential transfer of many drugs from prescription status to nonprescription status—a process known as Rx‐to‐OTC switching—could invigorate the self‐medication market in the coming decade. In this article, we examine the current OTC environment in seven of the world's major pharmaceutical markets (United States, France, Germany, Italy, Spain, United Kingdom, and Japan), and we discuss the trends that will likely fuel its growth.

Self-medication is a medication process based on complaints or symptoms up to the drug selection stage by themselves. Percentage of self-medication behavior in Kediri City increases every year so information about self-medication is needed. The class of drugs that can be used for self-medication are over the counter (OTC) drugs which are a class of over-the-counter drugs and limited over-the-counter drugs. These drugs can be purchased without a doctor's prescription, safe and effective if used according to the instructions for use. This activity aims to change the mindset and perspective of the community to be able to respond appropriately to how to use drugs by themselves. Community service activities in the form of counseling using the lecture method combined with a question and answer session, completed the pretest and posttest questionnaires, and last session is the distribution of leaflets regarding the use of OTC drugs. The target of the activity is the community in the Ngampel Village, Kediri City. There was an increase in knowledge about the use of OTC drugs in the community in Ngampel Village, Kediri City after being given counseling. We hope that after participating in counseling, people's knowledge will increase in using OTC drugs properly.

Organic anion-transporting polypeptide 4C1 (OATP4C1) is an organic anion transporter expressed in the basolateral membrane of the renal proximal tubules. It plays a major role in the urinary excretion of both exogenous drugs and endogenous compounds. Our previous studies have indicated the importance of OATP4C1 in pathologic and physiologic conditions; however, the majority of its pharmacologic characteristics remained unclear. Therefore, to provide essential information for clinical drug therapy decisions and drug development, we clarified drug interactions mediated by OATP4C1. To elucidate potential drug interactions via OATP4C1, we screened 53 representative drugs commonly used in clinical settings. Next, we evaluated the IC50 values of drugs that inhibited OATP4C1 by more than 50%. To apply our results to clinical settings, we calculated the drug-drug interaction (DDI) indices. The screening analysis using an OATP4C1-expressing cell system demonstrated that 22 out of 53 therapeutic drugs inhibited OATP4C1-mediated triiodothyronine transport. In particular, OATP4C1-mediated transport was strongly inhibited by 10 drugs. The IC50 values of 10 drugs-nicardipine, spironolactone, fluvastatin, crizotinib, levofloxacin, clarithromycin, ritonavir, saquinavir, quinidine, and verapamil-obtained in this study were 51, 53, 41, 24, 420, 200, 8.5, 4.3, 100, and 110 µM, respectively. The IC50 values of these drugs were higher than the plasma concentrations obtained in clinical practice. However, ritonavir showed the highest DDI index (1.9) for OATP4C1, suggesting that it may strongly influence this transporter and thus cause drug interactions seen in clinical settings. Our finding gives new insight into the role of OATP4C1 in clinical DDIs.

PXR interaction with p53: a meeting of two masters

Stimulatory effect on the transport mediated by organic anion transporting polypeptide 2B1

Histochemistry of Zinc and Copper

Drug transporters are widely expressed in organs and tissue barriers throughout human and animal bodies. Studies over the last two decades have identified various ATP-binding cassette and solute carrier transporters that play critical roles in the absorption, distribution, metabolism, and elimination of drugs and xenobiotics. This special section contains more than 20 original manuscripts and reviews that cover the most recent advances in the areas of drug transporter research, including the basic biology and function of transporters, expression of drug transporters in organ and tissue barriers, the mechanisms underlying regulation of transporter expression, transporter-mediated drug disposition in animal models, and the development and utilization of new technologies in drug transporter study, as well as pharmacokinetic modeling and simulation to assess transporter involvement in drug disposition and drug-drug interactions. We believe that the topics covered in this special section will advance our understanding of the roles of transporters in drug disposition, efficacy, and safety.

Water is one of the most crucial factors for enabling the normal functioning of physiological and biochemical processes in the body. An animal's body contains 40-75% water, depending on its age. The domestic donkey originates from the arid, dry regions of Eastern Africa. Such conditions do not allow for easy daily access to water sources. Except for pregnant females and mothers with young foals, other categories of donkeys do not go to drink water every day if the water sources are far away. Due to their high water needs, females with foals and pregnant donkeys go to water sources daily. A donkey can drink up to 25 liters of water in one session. In this way, they create water reserves and do not have to travel to distant water sources every day. For donkeys to drink water, it must be fresh and organoleptically clean. They will remain thirsty and refuse to drink stagnant or dirty water. A donkey needs 8-10 liters of water per 100 kg of body weight every day.