IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo
This document discusses multidrug resistant tuberculosis (MDR-TB) and the DOTS-Plus treatment guidelines. It provides background on the emergence of MDR-TB and the need for DOTS-Plus programs to treat patients resistant to first-line drugs. DOTS-Plus utilizes second-line drugs that are more toxic and difficult to administer. The standard Category IV regimen and dosages are described. Close monitoring is needed to detect adverse drug reactions early. Managing MDR-TB in special groups like pregnant women and those with HIV presents additional challenges.
This document describes a study that evaluated the pharmacokinetic/pharmacodynamic (PK/PD) relationships of a novel biotin carboxylase inhibitor called PD-0162819 against Haemophilus influenzae 3113 using in vitro infection models. Static concentration time-kill and one-compartment chemostat experiments were conducted. AUC/MIC ratio best explained efficacy compared to Cmax/MIC and T>MIC. Static effects and 99.9% killing were achieved at AUC/MIC values of 500 and 600, respectively. A semi-mechanistic PK/PD model was developed to describe bacterial growth and drug effects over time.
The document discusses pharmacokinetics and pharmacodynamics. It describes the four main processes of pharmacokinetics - absorption, distribution, metabolism and elimination - and how they determine the effects of drugs in the body. It also discusses factors that influence absorption and distribution of drugs. The document then covers pharmacodynamics concepts such as dose-response relationships, therapeutic indices, and interactions between drugs. Mechanisms of drug interactions including pharmacokinetic and pharmacodynamic interactions are explained. Common types of drug interactions and ways to prevent adverse drug effects are also summarized.
RNTCP guidelines for tuberculosis management by RxVichuZ! RxVichuZ
This document provides information on tuberculosis (TB) treatment guidelines according to the Revised National Tuberculosis Control Program (RNTCP) in India. It discusses the classification of anti-TB drugs into 5 groups and the classification of TB cases. It also summarizes the management principles and treatment regimens for multi-drug resistant TB, rifampin-resistant TB, mono-drug resistant TB, poly-drug resistant TB, extensive drug resistant TB, and INH-resistant TB as defined by the RNTCP. Standard intensive and continuation phase regimens are provided for each TB classification.
Paul Frohna -PK-PD Modeling and the QT issue (part 1- fda perspective)Paul Frohna
Dr. Paul Frohna, a biotech consultant with expertise in translational medicine and clinical pharmacology, presents an overview of the FDA's evolving perspectives on the QTc issue and the stand alone thorough QTc study.
Dose determination in preclinical and clinical studiesDrSahilKumar
This document discusses approaches for determining appropriate doses in preclinical and clinical studies. It covers considerations for in vitro, in vivo animal, and first-in-human clinical doses. For animal studies, a maximum tolerated dose is determined through dose range finding studies and acute toxicity studies. Regulatory toxicology studies use doses including a low dose at the no-observed-adverse-effect level, intermediate doses, and a high dose close to the maximum tolerated dose. For first-in-human studies, the estimated dose is typically 1/10 of the human equivalent dose calculated from the no-observed-adverse-effect level in the most appropriate animal species. Pharmacokinetic modeling and other drug properties may further inform safe starting doses
The presentation is about the dose selection for laboratory animal toxicology drug testing, explaining staged and staggered approach of dose selection.
Annual advances of traditional medicine toxicity in 2018LucyPi1
Abstract There were many researches concerning toxicology of traditional medicine (TM) and active natural products during the past 12 months. This annual toxicology review summarized different analysis methods of toxicology research, common evaluated models, toxic target organs, toxic mechanisms, and popular research issues and herbs in 2018. The emphasis was on hepatorenal toxicity induced by TM through cell apoptosis, metabolic disorder, oxidative stress, inflammatory damage, liver and renal fibrosis and even inducing carcinogenesis. Meanwhile, traditional herbs were listed in this review. Taken together, the herbs mentioned in this paper should be used with caution. Combination of TM, processing drugs, quality control and dose control can be used in the prevention of TM toxicology in the future.
Clinical pharmacology is a multidisciplinary science that studies the relationship between drugs and humans. It has a long history dating back to the 18th century. Clinical pharmacologists play important roles in patient care, teaching, and research. Their goals are to improve patient outcomes through rational drug use and the development of safer and more effective medicines. They conduct research studies in humans to better understand pharmacokinetics, pharmacodynamics, and pharmacogenetics which can help optimize drug therapy for individuals.
This document describes a study that evaluated the pharmacokinetic/pharmacodynamic (PK/PD) relationships of a novel biotin carboxylase inhibitor called PD-0162819 against Haemophilus influenzae 3113 using in vitro infection models. Static concentration time-kill and one-compartment chemostat experiments were conducted. AUC/MIC ratio best explained efficacy compared to Cmax/MIC and T>MIC. Static effects and 99.9% killing were achieved at AUC/MIC values of 500 and 600, respectively. A semi-mechanistic PK/PD model was developed to describe bacterial growth and drug effects over time.
The document discusses pharmacokinetics and pharmacodynamics. It describes the four main processes of pharmacokinetics - absorption, distribution, metabolism and elimination - and how they determine the effects of drugs in the body. It also discusses factors that influence absorption and distribution of drugs. The document then covers pharmacodynamics concepts such as dose-response relationships, therapeutic indices, and interactions between drugs. Mechanisms of drug interactions including pharmacokinetic and pharmacodynamic interactions are explained. Common types of drug interactions and ways to prevent adverse drug effects are also summarized.
RNTCP guidelines for tuberculosis management by RxVichuZ! RxVichuZ
This document provides information on tuberculosis (TB) treatment guidelines according to the Revised National Tuberculosis Control Program (RNTCP) in India. It discusses the classification of anti-TB drugs into 5 groups and the classification of TB cases. It also summarizes the management principles and treatment regimens for multi-drug resistant TB, rifampin-resistant TB, mono-drug resistant TB, poly-drug resistant TB, extensive drug resistant TB, and INH-resistant TB as defined by the RNTCP. Standard intensive and continuation phase regimens are provided for each TB classification.
Paul Frohna -PK-PD Modeling and the QT issue (part 1- fda perspective)Paul Frohna
Dr. Paul Frohna, a biotech consultant with expertise in translational medicine and clinical pharmacology, presents an overview of the FDA's evolving perspectives on the QTc issue and the stand alone thorough QTc study.
Dose determination in preclinical and clinical studiesDrSahilKumar
This document discusses approaches for determining appropriate doses in preclinical and clinical studies. It covers considerations for in vitro, in vivo animal, and first-in-human clinical doses. For animal studies, a maximum tolerated dose is determined through dose range finding studies and acute toxicity studies. Regulatory toxicology studies use doses including a low dose at the no-observed-adverse-effect level, intermediate doses, and a high dose close to the maximum tolerated dose. For first-in-human studies, the estimated dose is typically 1/10 of the human equivalent dose calculated from the no-observed-adverse-effect level in the most appropriate animal species. Pharmacokinetic modeling and other drug properties may further inform safe starting doses
The presentation is about the dose selection for laboratory animal toxicology drug testing, explaining staged and staggered approach of dose selection.
Annual advances of traditional medicine toxicity in 2018LucyPi1
Abstract There were many researches concerning toxicology of traditional medicine (TM) and active natural products during the past 12 months. This annual toxicology review summarized different analysis methods of toxicology research, common evaluated models, toxic target organs, toxic mechanisms, and popular research issues and herbs in 2018. The emphasis was on hepatorenal toxicity induced by TM through cell apoptosis, metabolic disorder, oxidative stress, inflammatory damage, liver and renal fibrosis and even inducing carcinogenesis. Meanwhile, traditional herbs were listed in this review. Taken together, the herbs mentioned in this paper should be used with caution. Combination of TM, processing drugs, quality control and dose control can be used in the prevention of TM toxicology in the future.
Clinical pharmacology is a multidisciplinary science that studies the relationship between drugs and humans. It has a long history dating back to the 18th century. Clinical pharmacologists play important roles in patient care, teaching, and research. Their goals are to improve patient outcomes through rational drug use and the development of safer and more effective medicines. They conduct research studies in humans to better understand pharmacokinetics, pharmacodynamics, and pharmacogenetics which can help optimize drug therapy for individuals.
RNTCP in India has gone a lot of updates in the resent times. The recent updates in RNTCP in India have been summarised in this presentation. Management of Drug sensitive and Drug Resistant TB have been included in the presentation.
This document discusses advances in monitoring pharmacotherapeutics and drug delivery system design. It begins with definitions of pharmacotherapy and the need for monitoring it to ensure safe and effective use of drugs. It then discusses factors like adverse drug reactions, rational drug use, and improving patient compliance. Recent advances in monitoring discussed include microscopy techniques for examining drug fate and distribution in tissues. The document also discusses trends in pharmaceutical product design like controlled release and targeted delivery systems. Specific advances highlighted include prodrug approaches, nanocarrier systems, and delivery methods like Ocusert inserts and buccal patches.
The document discusses the process of drug discovery and development. It has 5 main stages: drug discovery, pre-clinical testing, clinical trials (phases I-III), regulatory approval, and post-marketing surveillance. Drug discovery involves screening compounds for pharmacological activity through random testing, serendipitous findings, or rational drug design. Pre-clinical testing involves extensive animal studies to evaluate safety, efficacy, and adverse effects. Clinical trials in humans have 3 phases to further assess these factors before regulatory approval and marketing of the drug. Post-approval monitoring continues to study long-term safety and efficacy.
The document discusses repurposed drugs and safety monitoring during the COVID-19 pandemic. It describes how known drugs are being used in a different context than originally approved to treat COVID-19. Two such drugs are chloroquine/hydroxychloroquine and remdesivir. While initial studies of hydroxychloroquine showed promise in vitro, subsequent large trials found no significant benefits. Remdesivir was found to decrease recovery time based on NIH trials but the WHO recommends against its use due to low certainty of benefit. Both drugs present drug interaction risks that require careful safety monitoring.
This document introduces key concepts in pharmacology. It defines drug, pharmacology, clinical pharmacology, and therapeutics. An ideal drug is effective, safe, and selective, but no drug is truly ideal. The objective of drug therapy is to provide maximum benefit with minimum harm. How individuals respond depends on administration, pharmacokinetics, pharmacodynamics, and individual variations.
The document outlines the key stages of drug discovery:
1. Target identification involves finding the specific biomolecule target of a drug.
2. Target validation helps evaluate the potential of a target through assays and screening to find initial hits.
3. Lead discovery uses screening methods like molecular modeling or combinational chemistry to identify initial compounds ("leads") that interact with the target.
4. Lead optimization chemically modifies the leads to improve efficacy, safety and other drug properties.
5. Pre-clinical safety involves animal testing, toxicity studies and formulation before clinical trials in humans.
The bacteria that cause tuberculosis (TB) can develop resistance to the antimicrobial drugs used to cure the disease. Multidrug-resistant TB (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs.
The 2 reasons why multidrug resistance continues to emerge and spread are mismanagement of TB treatment and person-to-person transmission. Most people with TB are cured by a strictly followed, 6-month drug regimen that is provided to patients with support and supervision. Inappropriate or incorrect use of antimicrobial drugs, or use of ineffective formulations of drugs (such as use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals.
In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited and expensive, recommended medicines are not always available, and patients experience many adverse effects from the drugs. In some cases even more severe drug-resistant TB may develop. Extensively drug-resistant TB, XDR-TB, is a form of multidrug-resistant TB with additional resistance to more anti-TB drugs that therefore responds to even fewer available medicines. It has been reported in 117 countries worldwide.
Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs or detect resistance patterns. These tests can be molecular in type (such as Xpert MTB/RIF) or else culture-based. Molecular techniques can provide results within hours and have been successfully implemented even in low resource settings.
New WHO recommendations aim to speed up detection and improve treatment outcomes for MDR-TB through use of a novel rapid diagnostic test and a shorter, cheaper treatment regimen. At less than US$ 1000 per patient, the new treatment regimen can be completed in 9–12 months. Not only is it less expensive than current regimens, but it is also expected to improve outcomes and potentially decrease deaths due to better adherence to treatment and reduced loss to follow-up.
Solutions to control drug-resistant TB are to:
cure the TB patient the first time around
provide access to diagnosis
ensure adequate infection control in facilities where patients are treated
ensure the appropriate use of recommended second-line drugs.
In 2015, an estimated 480 000 people worldwide developed MDR-TB, and an additional 100 000 people with rifampicin-resistant TB were also newly eligible for MDR-TB treatment. India, China, and the Russian Federation accounted for 45% of the 580 000 cases. It is estimated that about 9.5% of these cases were XDR-TB.
The document provides an overview of the drug development process from discovery of a lead compound through clinical trials and regulatory approval. Key steps include identifying a biological target, using high-throughput screening to discover lead compounds, conducting preclinical testing on lead compounds, and then Phase I-III clinical trials on humans to test safety and efficacy before regulatory approval and marketing. The process takes over a decade and costs billions due to extensive testing required to bring a new medicine to patients.
This document discusses multidrug-resistant tuberculosis (MDR-TB), which kills over 5,000 people per day globally and is a major public health crisis. MDR-TB is highly prevalent in many developing countries and is increasingly difficult to treat due to genetic mutations that make the tuberculosis bacteria resistant to multiple drugs. Proper treatment requires identifying the right combination of at least 4-6 effective drugs through culture and sensitivity testing, directly observing patients to ensure proper adherence, and treating for a minimum of 18-24 months. However, MDR-TB treatment faces many challenges including limited diagnostic capacity, improper prescribing practices, and socioeconomic factors affecting patient compliance.
This document discusses fixed dose drug combinations (FDDCs), including their definitions, types, rationality, advantages, and disadvantages. It defines FDDCs as combinations of two or more active pharmaceutical ingredients formulated as a single medicine. FDDCs can be rational if they have complementary mechanisms of action, decrease resistance, and increase efficacy and compliance while decreasing adverse effects. However, irrational FDDCs lack pharmacological justification and may increase side effects and costs without additional benefit. The document also notes issues with overpromotion of irrational FDDCs in India and efforts to better regulate these combinations.
1) The document discusses principles of antimicrobial therapy, including how antimicrobial drugs work by selectively killing microorganisms without harming host cells.
2) Selection of the best antimicrobial agent requires identifying the infecting organism, determining its drug susceptibility, considering the infection site and patient factors like immunity or organ function, and weighing the drug's safety, cost and ability to reach the infection site.
3) Antimicrobial therapy aims to rapidly identify pathogens, start immediate empiric treatment when needed, and later adjust therapy based on identification and susceptibility results while considering host barriers, drug properties, and toxicity risks.
The document discusses MARDI's research on herbal medicines and toxicology studies. It notes that while herbs are commonly used as traditional medicines, safety issues exist like contamination, adverse herb effects, and herb-drug interactions. MARDI conducts research to identify safe and effective herbal therapies, including toxicity studies. The aim is to commercialize Malaysian herbs by meeting regulatory standards, resolving safety issues, and integrating herbal medicine into the healthcare system. Standard documents like GMP certificates and toxicity test reports are needed to export herbal products.
Comparison of Pharmacology and Toxicologyshabeel pn
- Pharmacology is the study of drugs and their effects on the body, while toxicology is the study of harmful chemicals and their health effects.
- Key concepts in both fields include dose, route of exposure/administration, and dose-response relationships, though exposures are often involuntary in toxicology versus voluntary drug administration.
- Both disciplines examine distribution, metabolism, and excretion of substances in the body, and interactions between substances can be additive, synergistic, or antagonistic.
This document provides an introduction to the field of pharmacology. It defines pharmacology as the science of drug action and explains that it has two main branches: pharmacokinetics and pharmacodynamics. Pharmacokinetics refers to how the body affects drugs, involving absorption, distribution, metabolism and excretion of drugs. Pharmacodynamics refers to how drugs affect the body by binding to receptors to elicit therapeutic or adverse effects. The document discusses important pharmacokinetic concepts like volume of distribution, half-life and clearance that determine drug dosing. It also explains the process of drug metabolism and excretion. Overall, the document outlines key concepts in pharmacology to understand drug action and properties.
Clinical pharmacology studies how medications act in the human body. It has several key areas of focus: pharmacodynamics examines the effects of drugs and their mechanisms of action; pharmacokinetics studies how the body absorbs, distributes, metabolizes and eliminates drugs. Pharmacogenetics explores genetic factors influencing individual responses to medications. Receptors play an important role in how drugs produce their effects, and drugs can act through different receptor types or mechanisms to produce their intended or side effects.
Pharmacology is the study of how drugs interact with living organisms. It involves studying the physicochemical properties, mechanisms of action, absorption, distribution, metabolism, and excretion of drugs, as well as their clinical uses and adverse effects. Pharmacology has two main divisions: pharmacodynamics, which is what the drug does to the body, and pharmacokinetics, which is what the body does to the drug. The scope of pharmacology includes areas like chemotherapy, toxicology, therapeutics, pharmacoeconomics, pharmacogenomics, pharmacoepidemiology, pharmacotherapeutics, pharmacovigilance, and clinical pharmacology.
This document discusses the management of tuberculosis (TB) and multidrug-resistant TB (MDR TB). It provides an overview of TB trends worldwide and in Canada, including risk factors. It describes the medical management of TB, including diagnosis, treatment principles, drug susceptibility testing, and treatment duration. The document presents two case studies of patients with poly-resistant and MDR TB to illustrate their complex management and treatment challenges over many months to years. Management of MDR TB requires individualized treatment based on drug susceptibility, multiple drugs including intravenous options, and strict adherence to therapy.
The document discusses definitions, types, epidemiology, causes, and management of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). It defines MDR-TB as resistance to at least isoniazid and rifampicin, and XDR-TB as MDR-TB plus resistance to a fluoroquinolone and one second-line injectable drug. It notes that MDR-TB prevalence is highest in previously treated patients and discusses the role of laboratory testing in designing effective treatment regimens. It provides guidelines for managing MDR/XDR-TB, including using a combination of effective drugs and directly observed therapy.
This document provides an overview of multidrug-resistant tuberculosis (MDR TB). It defines the different types of drug-resistant TB and discusses the epidemiology and mechanisms of drug resistance. It emphasizes the importance of proper diagnosis and treatment for managing drug-resistant TB. The key points are that improper or incomplete treatment can cause drug resistance to develop, MDR TB requires testing to identify resistance and an individualized treatment regimen using second-line drugs, and treatment must be closely monitored for at least 18-24 months.
RNTCP in India has gone a lot of updates in the resent times. The recent updates in RNTCP in India have been summarised in this presentation. Management of Drug sensitive and Drug Resistant TB have been included in the presentation.
This document discusses advances in monitoring pharmacotherapeutics and drug delivery system design. It begins with definitions of pharmacotherapy and the need for monitoring it to ensure safe and effective use of drugs. It then discusses factors like adverse drug reactions, rational drug use, and improving patient compliance. Recent advances in monitoring discussed include microscopy techniques for examining drug fate and distribution in tissues. The document also discusses trends in pharmaceutical product design like controlled release and targeted delivery systems. Specific advances highlighted include prodrug approaches, nanocarrier systems, and delivery methods like Ocusert inserts and buccal patches.
The document discusses the process of drug discovery and development. It has 5 main stages: drug discovery, pre-clinical testing, clinical trials (phases I-III), regulatory approval, and post-marketing surveillance. Drug discovery involves screening compounds for pharmacological activity through random testing, serendipitous findings, or rational drug design. Pre-clinical testing involves extensive animal studies to evaluate safety, efficacy, and adverse effects. Clinical trials in humans have 3 phases to further assess these factors before regulatory approval and marketing of the drug. Post-approval monitoring continues to study long-term safety and efficacy.
The document discusses repurposed drugs and safety monitoring during the COVID-19 pandemic. It describes how known drugs are being used in a different context than originally approved to treat COVID-19. Two such drugs are chloroquine/hydroxychloroquine and remdesivir. While initial studies of hydroxychloroquine showed promise in vitro, subsequent large trials found no significant benefits. Remdesivir was found to decrease recovery time based on NIH trials but the WHO recommends against its use due to low certainty of benefit. Both drugs present drug interaction risks that require careful safety monitoring.
This document introduces key concepts in pharmacology. It defines drug, pharmacology, clinical pharmacology, and therapeutics. An ideal drug is effective, safe, and selective, but no drug is truly ideal. The objective of drug therapy is to provide maximum benefit with minimum harm. How individuals respond depends on administration, pharmacokinetics, pharmacodynamics, and individual variations.
The document outlines the key stages of drug discovery:
1. Target identification involves finding the specific biomolecule target of a drug.
2. Target validation helps evaluate the potential of a target through assays and screening to find initial hits.
3. Lead discovery uses screening methods like molecular modeling or combinational chemistry to identify initial compounds ("leads") that interact with the target.
4. Lead optimization chemically modifies the leads to improve efficacy, safety and other drug properties.
5. Pre-clinical safety involves animal testing, toxicity studies and formulation before clinical trials in humans.
The bacteria that cause tuberculosis (TB) can develop resistance to the antimicrobial drugs used to cure the disease. Multidrug-resistant TB (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs.
The 2 reasons why multidrug resistance continues to emerge and spread are mismanagement of TB treatment and person-to-person transmission. Most people with TB are cured by a strictly followed, 6-month drug regimen that is provided to patients with support and supervision. Inappropriate or incorrect use of antimicrobial drugs, or use of ineffective formulations of drugs (such as use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals.
In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited and expensive, recommended medicines are not always available, and patients experience many adverse effects from the drugs. In some cases even more severe drug-resistant TB may develop. Extensively drug-resistant TB, XDR-TB, is a form of multidrug-resistant TB with additional resistance to more anti-TB drugs that therefore responds to even fewer available medicines. It has been reported in 117 countries worldwide.
Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs or detect resistance patterns. These tests can be molecular in type (such as Xpert MTB/RIF) or else culture-based. Molecular techniques can provide results within hours and have been successfully implemented even in low resource settings.
New WHO recommendations aim to speed up detection and improve treatment outcomes for MDR-TB through use of a novel rapid diagnostic test and a shorter, cheaper treatment regimen. At less than US$ 1000 per patient, the new treatment regimen can be completed in 9–12 months. Not only is it less expensive than current regimens, but it is also expected to improve outcomes and potentially decrease deaths due to better adherence to treatment and reduced loss to follow-up.
Solutions to control drug-resistant TB are to:
cure the TB patient the first time around
provide access to diagnosis
ensure adequate infection control in facilities where patients are treated
ensure the appropriate use of recommended second-line drugs.
In 2015, an estimated 480 000 people worldwide developed MDR-TB, and an additional 100 000 people with rifampicin-resistant TB were also newly eligible for MDR-TB treatment. India, China, and the Russian Federation accounted for 45% of the 580 000 cases. It is estimated that about 9.5% of these cases were XDR-TB.
The document provides an overview of the drug development process from discovery of a lead compound through clinical trials and regulatory approval. Key steps include identifying a biological target, using high-throughput screening to discover lead compounds, conducting preclinical testing on lead compounds, and then Phase I-III clinical trials on humans to test safety and efficacy before regulatory approval and marketing. The process takes over a decade and costs billions due to extensive testing required to bring a new medicine to patients.
This document discusses multidrug-resistant tuberculosis (MDR-TB), which kills over 5,000 people per day globally and is a major public health crisis. MDR-TB is highly prevalent in many developing countries and is increasingly difficult to treat due to genetic mutations that make the tuberculosis bacteria resistant to multiple drugs. Proper treatment requires identifying the right combination of at least 4-6 effective drugs through culture and sensitivity testing, directly observing patients to ensure proper adherence, and treating for a minimum of 18-24 months. However, MDR-TB treatment faces many challenges including limited diagnostic capacity, improper prescribing practices, and socioeconomic factors affecting patient compliance.
This document discusses fixed dose drug combinations (FDDCs), including their definitions, types, rationality, advantages, and disadvantages. It defines FDDCs as combinations of two or more active pharmaceutical ingredients formulated as a single medicine. FDDCs can be rational if they have complementary mechanisms of action, decrease resistance, and increase efficacy and compliance while decreasing adverse effects. However, irrational FDDCs lack pharmacological justification and may increase side effects and costs without additional benefit. The document also notes issues with overpromotion of irrational FDDCs in India and efforts to better regulate these combinations.
1) The document discusses principles of antimicrobial therapy, including how antimicrobial drugs work by selectively killing microorganisms without harming host cells.
2) Selection of the best antimicrobial agent requires identifying the infecting organism, determining its drug susceptibility, considering the infection site and patient factors like immunity or organ function, and weighing the drug's safety, cost and ability to reach the infection site.
3) Antimicrobial therapy aims to rapidly identify pathogens, start immediate empiric treatment when needed, and later adjust therapy based on identification and susceptibility results while considering host barriers, drug properties, and toxicity risks.
The document discusses MARDI's research on herbal medicines and toxicology studies. It notes that while herbs are commonly used as traditional medicines, safety issues exist like contamination, adverse herb effects, and herb-drug interactions. MARDI conducts research to identify safe and effective herbal therapies, including toxicity studies. The aim is to commercialize Malaysian herbs by meeting regulatory standards, resolving safety issues, and integrating herbal medicine into the healthcare system. Standard documents like GMP certificates and toxicity test reports are needed to export herbal products.
Comparison of Pharmacology and Toxicologyshabeel pn
- Pharmacology is the study of drugs and their effects on the body, while toxicology is the study of harmful chemicals and their health effects.
- Key concepts in both fields include dose, route of exposure/administration, and dose-response relationships, though exposures are often involuntary in toxicology versus voluntary drug administration.
- Both disciplines examine distribution, metabolism, and excretion of substances in the body, and interactions between substances can be additive, synergistic, or antagonistic.
This document provides an introduction to the field of pharmacology. It defines pharmacology as the science of drug action and explains that it has two main branches: pharmacokinetics and pharmacodynamics. Pharmacokinetics refers to how the body affects drugs, involving absorption, distribution, metabolism and excretion of drugs. Pharmacodynamics refers to how drugs affect the body by binding to receptors to elicit therapeutic or adverse effects. The document discusses important pharmacokinetic concepts like volume of distribution, half-life and clearance that determine drug dosing. It also explains the process of drug metabolism and excretion. Overall, the document outlines key concepts in pharmacology to understand drug action and properties.
Clinical pharmacology studies how medications act in the human body. It has several key areas of focus: pharmacodynamics examines the effects of drugs and their mechanisms of action; pharmacokinetics studies how the body absorbs, distributes, metabolizes and eliminates drugs. Pharmacogenetics explores genetic factors influencing individual responses to medications. Receptors play an important role in how drugs produce their effects, and drugs can act through different receptor types or mechanisms to produce their intended or side effects.
Pharmacology is the study of how drugs interact with living organisms. It involves studying the physicochemical properties, mechanisms of action, absorption, distribution, metabolism, and excretion of drugs, as well as their clinical uses and adverse effects. Pharmacology has two main divisions: pharmacodynamics, which is what the drug does to the body, and pharmacokinetics, which is what the body does to the drug. The scope of pharmacology includes areas like chemotherapy, toxicology, therapeutics, pharmacoeconomics, pharmacogenomics, pharmacoepidemiology, pharmacotherapeutics, pharmacovigilance, and clinical pharmacology.
This document discusses the management of tuberculosis (TB) and multidrug-resistant TB (MDR TB). It provides an overview of TB trends worldwide and in Canada, including risk factors. It describes the medical management of TB, including diagnosis, treatment principles, drug susceptibility testing, and treatment duration. The document presents two case studies of patients with poly-resistant and MDR TB to illustrate their complex management and treatment challenges over many months to years. Management of MDR TB requires individualized treatment based on drug susceptibility, multiple drugs including intravenous options, and strict adherence to therapy.
Similar to IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo
The document discusses definitions, types, epidemiology, causes, and management of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). It defines MDR-TB as resistance to at least isoniazid and rifampicin, and XDR-TB as MDR-TB plus resistance to a fluoroquinolone and one second-line injectable drug. It notes that MDR-TB prevalence is highest in previously treated patients and discusses the role of laboratory testing in designing effective treatment regimens. It provides guidelines for managing MDR/XDR-TB, including using a combination of effective drugs and directly observed therapy.
This document provides an overview of multidrug-resistant tuberculosis (MDR TB). It defines the different types of drug-resistant TB and discusses the epidemiology and mechanisms of drug resistance. It emphasizes the importance of proper diagnosis and treatment for managing drug-resistant TB. The key points are that improper or incomplete treatment can cause drug resistance to develop, MDR TB requires testing to identify resistance and an individualized treatment regimen using second-line drugs, and treatment must be closely monitored for at least 18-24 months.
This document discusses rational use of over-the-counter (OTC) medications. It provides examples of common OTC drug categories and explains that rational use means using the appropriate medication, in the proper dose, for the right duration and indication. Irrational or improper use can lead to antimicrobial resistance, adverse reactions, financial costs, and erosion of patient confidence in the healthcare system. Factors contributing to irrational use include lack of knowledge and unethical drug promotion. Improving rational use requires guidelines, education, availability of essential medicines, and eliminating financial incentives for improper prescribing. Several examples of irrational fixed-dose drug combinations are also provided that combine drugs with different mechanisms or indications.
The document provides an overview of the National Tuberculosis Elimination Programme (NTEP) in India. It discusses the evolution and structure of NTEP, as well as the STOP TB and End TB strategies. It outlines the treatment regimens for drug-sensitive and drug-resistant TB, including special considerations for pregnancy, lactation, children, and those with HIV/diabetes. It also describes the Nikshay surveillance system and 99DOTS adherence monitoring program. The overall goal of NTEP is to eliminate TB in India by 2025 through improved detection, treatment, and prevention.
Recent advances in management of tuberculosis finalVaibhav Watts
1) The document summarizes recent updates to WHO guidelines for the treatment and management of tuberculosis, including recommendations for shorter MDR-TB regimens, the use of bedaquiline and delamanid, and starting ART for all TB/HIV patients.
2) It also discusses changes to the Indian RNTCP guidelines in 2017, including implementing a daily drug regimen over intermittent dosing, modifications for TB/HIV coinfection treatment, and extending the continuation phase for certain TB types.
3) New drugs and regimens for both drug-susceptible and drug-resistant TB are highlighted, as well as the increased use of molecular diagnostic tests.
The document summarizes guidelines from the WHO on treating drug-resistant tuberculosis. It provides definitions for various drug-resistant TB types and recommendations for treatment regimens. For rifampicin-susceptible, isoniazid-resistant TB, it recommends a 6-month regimen containing rifampicin, ethambutol, pyrazinamide, and levofloxacin. For multidrug- or rifampicin-resistant TB, it recommends a 9-12 month all-oral regimen containing bedaquiline when resistance to fluoroquinolones has been excluded and the patient has not been exposed to the regimen's second-line drugs for over 1 month. The guidelines are based on evidence
This study evaluated the utilization pattern of antibiotics at a tertiary care teaching hospital in North Karnataka, India by analyzing 250 patient prescriptions. The most commonly prescribed antibiotic classes were cephalosporins and fluoroquinolones. Comparison to clinical guidelines found deviations in diagnostic testing and treatment. For many conditions like pneumonia and bronchitis, sputum testing was not performed before antibiotic prescription. Overall antibiotic use could be more rational by adhering closer to treatment guidelines. Pharmacist involvement in drug use evaluation programs may help improve antibiotic use and patient outcomes.
Multi-drug resistant tuberculosis (MDR-TB) arises from inadequate or incomplete treatment that allows bacteria to develop resistance to multiple drugs. MDR-TB bacteria resist key first-line drugs like isoniazid and rifampin and require lengthy treatment with second-line drugs. The development of drug resistance threatens global TB control and highlights the need for improved diagnostics, treatment monitoring, and antibiotic stewardship to limit resistance.
Recent advances in multi drug resistant tuberculosis &rntcpNursing Path
Tuberculosis persists as a global public health problem, with multi-drug resistant TB found in many countries including India. Studies have found MDR TB levels between 2-14% in some areas of India. The emergence of drug resistant TB can be prevented through adequate case finding, prompt diagnosis and effective treatment under DOTS programs. DOTS Plus programs were established to diagnose and treat MDR TB through quality assured drug susceptibility testing and the use of second line drugs administered properly under DOTS Plus guidelines. Contact management is also important to prevent the spread of MDR TB.
RNTCP.pptx revised national tuberculosis programSupriyaBatwalkar
Tuberculosis is one of the top 10 causes of death worldwide, with 10.4 million new cases and 1.7 million deaths in 2016. India has the highest TB burden globally, accounting for over one-fifth of new cases. The document discusses the history and strategies of India's National Tuberculosis Control Programme and Revised National Tuberculosis Control Programme, including the introduction of DOTS strategy. It provides data on TB incidence, prevalence, and mortality in India as well as information on diagnosis, treatment regimens, drug-resistant TB, and the National Strategic Plan 2017-2025's goals to eliminate TB in India.
DOTS (Directly Observed Treatment Short Course) is a WHO-recommended strategy for tuberculosis (TB) treatment involving direct observation of patients taking anti-TB drugs. It ensures patients take the right drugs, at the right doses, and at the right intervals, observed by a healthcare worker or community member. DOTS includes a standardized short course combination chemotherapy regimen, case detection by sputum smear microscopy, an uninterrupted supply of drugs, and a recording and reporting system to assess treatment results. Successful implementation of DOTS requires government commitment and funding for long-term TB control.
This document provides an outline and presentation on multi-drug resistant tuberculosis (MDR-TB). It defines MDR-TB as resistance to at least isoniazid and rifampicin. Globally in 2018, there were an estimated half million new cases of rifampicin-resistant TB and 3.4% of new TB cases had MDR-TB. Drug resistance is generated through spontaneous mutations and having previous TB treatment or exposure increases risk. Diagnosis involves smear, Xpert, culture and line probe assays. Treatment involves longer regimens with second line drugs for 18-20 months.
An Essential Drug List, also known as a core drug list or medication list, is a carefully selected inventory of medications that are deemed essential for addressing the most prevalent health conditions within a specific population or country. It serves as a key component of national drug policies and pharmaceutical programs, ensuring the availability, accessibility, and affordability of essential medicines. The list is typically developed based on rigorous criteria, taking into consideration the medications' safety, efficacy, cost-effectiveness, and suitability for primary healthcare settings.
Rational Drug Therapy refers to the systematic and evidence-based approach to prescribing medications, aiming to maximize therapeutic benefits while minimizing the risk of adverse effects. It involves following established therapeutic guidelines and clinical protocols to ensure that medications are prescribed in a manner that is appropriate for the patient's condition, taking into account factors such as age, weight, co-existing conditions, drug interactions, and individual response. Rational drug therapy promotes the use of medications based on sound scientific evidence, emphasizing the principles of efficacy, safety, and cost-effectiveness to optimize patient outcomes and improve overall healthcare quality.
The National Tuberculosis Control Programme and Revised National Tuberculosis Control Programme were implemented in India to deal with the tuberculosis problem. The objectives are to reduce infection rates through case detection, treatment, and BCG vaccination. In the 1990s, the programmes suffered from management issues and inadequate funding. The RNTCP adopted the DOTS strategy recommended by the WHO to improve cure rates and case detection through direct observation of treatment. Treatment involves a two-phase regimen administered under direct observation at least initially. Nurses play an important role in treating TB patients through home visits, education, and contact screening.
The document discusses tuberculosis (TB) treatment, including:
1. The goals of TB treatment are to cure patients, prevent death from active TB, prevent relapse, decrease transmission, and prevent acquired drug resistance.
2. Directly Observed Treatment, Short-course (DOTS) involves decentralized diagnosis and treatment based on existing health facilities, good program management, and an evaluation system.
3. Treatment of drug-resistant TB and extensively drug-resistant TB (XDR-TB) requires specialized multi-drug regimens using second-line drugs.
Introduction to rational use of drugs and role of pharmacist in rational use...Adhin Antony Xavier
This document discusses strategies for promoting rational use of drugs in healthcare systems. It recommends establishing a national drug regulatory authority to oversee drug quality, developing treatment guidelines and an essential drug list. Healthcare professionals should be provided drug information and undergo continuing education on rational prescribing. Generic names should be used and drugs prescribed according to their intended therapeutic uses and appropriate dosages. Quality of drugs must be ensured and irrational self-medication discouraged through public education. Monitoring drug use through indicators can help evaluate prescribing practices and promote rational drug utilization.
The presentation included treatment principles of Tuberculosis with first line drugs as per the recent RNTCP guidelines in India on DAILY ATT.
Similar to IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo (20)
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Correlation of Estrogen and Progesterone Receptor expression in Breast Canceriosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...iosrphr_editor
The current study was carried out in District Abbottabad aimed to determine the common urinary
tract infections in local community to determine the epidemiology of significant diseases in asymptomatic patients
of renal disorder. In this study a total of 1000 urine samples were examined during 3rd February to 1st April 2015
from patients attending Ayub Teaching Hospital Abbottabad by using dipstick and microscopic analysis of urine.
There were 638 females and 362 males patients examined during this period. The range of age groups is between
1.5 years to 80 years. Results of this study was reported as Pyuria 11%, Proteinuria 21.1%, Hematuria 10.4%,
Epithelial Cells 8.2%, pH 7.8 %, Granular casts 7.3%, Triple phosphate 6.6%, Calcium oxalate 6.4%, Glycosuria
6.3%, Bacteria 6.2% and mucous 4.1%. This study concludes that routing urinalysis should be performed for all
individuals to diagnose the asymptomatic diseases that will help in simple therapeutic measurements as urinalysis
is a simple step to determine the root of Urinary tract disorders.
Chest sonography images in neonatal r.d.s. And proposed gradingiosrphr_editor
BACKGROUND : Lung sonography has been used to monitor the patients of R.D.S. in
N.I.C.U. in recent times.
AIMS : To Describe and Grade the changes of R.D.S. by lung sonography.
SETTING & DESIGN : Tertiary care institutional set up in a rural medical college.
STUDY DURATION : September 2014 to May 2015. Follow-up variable, upto 2 weeks.
PROSPECTIVE, ANALYTICAL STUDY.
MATERIALS AND METHODS -This was a single institute study approved by the institutional ethics
committee. Prior informed consent was obtained from the parents. 100 consecutive patients admitted in
N.I.C.U. WITH gestational age < 36 weeks with respiratory complaints were enrolled. Chest x-ray was
obtained within few hours of admission and lung sonography was performed within 24 hours. Follow – up
sonography was performed as and when necessary. Sonography image was graded and correlated with chest
xray and clinical picture
The Comprehensive Review on Fat Soluble Vitaminsiosrphr_editor
This review article deals with brief description of fat soluble vitamins with figures and tables
showing statistical analytical data duly quoting the references wherever necessary. The word “soluble” actually
means “able to be dissolved.” Whether a vitamin is classified as 'fat-soluble' or 'water-soluble' has to do with
how the vitamin is absorbed, stored and removed from the body. Vitamins are tiny organic compounds with a
huge impact on the health and well-being of the body. The body needs a small amount of fat soluble vitamins in
order to stay in optimal health. Fat soluble vitamins play an important role in keeping the body healthy and
functioning from immune system and muscle and heart function, easy flow and clotting of blood as well as eye
health. They are critical to health and wellness–particularly reproductive health and wellness. Low-fat, no-fat
and vegan diets are woefully lacking in fat soluble vitamins. However a diet based on traditional foods can
naturally provide these vitamins. Science is still learning about many of the functions of vitamins. "Too much
vitamin A, D, or K can lead to increased levels that are unhealthy and can cause serious health consequences.
Diseased conditions leading to decreased fat absorption leads to decreased absorption of vitamins. The fatsoluble
vitamins work most safely and effectively when obtained them from natural foods within the context of a
diet rich in all their synergistic partners. If fat soluble vitamins are stored for lengthy time they generate threat
for toxicity than water soluble vitamins and such situation even aggravated, provided they are consumed in
excess. Vitamin products, above the legal limits are not considered food supplements and must be registered as
prescription or non-prescription (over-the-counter drugs) due to their potential side effects. Vitamin A and E
supplements do not provide health benefits for healthy individuals, instead they may enhance mortality, and it is
held proved that beta-carotene supplements can be harmful to smokers
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
The document describes a case study of an 18-year-old female patient who developed toxic epidermal necrolysis as a severe adverse reaction to the drug sulfasalazine, which she had been taking for ankylosing spondylitis. She was admitted to the intensive care unit and treated with high dose corticosteroids, fluid replacement, and supportive care. She improved with treatment and was discharged with only post-inflammatory hypopigmentation.
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
Hemolytic disease of newborn (HDN) is an important cause of hyperbilirubinemia in the
neonatal period,and delayed diagnosis and treatment may lead to permanent brain damage. Traditional
neonatal treatment of HDN is intensive phototherapy and exchange transfusion.Intravenous
immunoglobulin(IVIgG) has been introduced as an alternative therapy to exchange transfusion. This study was
conducted to assess the effect of IVIG in HDN .
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.iosrphr_editor
Nervous fibrolipomatous hamartoma is said to be a rare tumor-like condition involving the peripheral
nerves,in which the epineurium and perineurium are enlarged and distorted by excess of fatty and fibrous tissue
s that infiltrate between and around nerve boundaries. The median nerve is more likely to develop a hamartoma
than other nerves with a predilection for the carpal tunnel.
A fibrolipomatous hamartoma – is a rare, benign, congenital lesion most commonly found in the median nerve,
usually at the level of the wrist or hand.
We report a case of this rare condition in ulnar nerve.
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...iosrphr_editor
This study examined self-medication practices for oral health problems among dental patients in Bangalore, India. The study found that 100% of the 175 dental patients surveyed practiced self-medication. Toothache was the most common triggering factor reported. Analgesics and herbal remedies were commonly used for self-treatment. Most participants consulted pharmacists for advice on self-medication and would see a dentist only if problems persisted after self-medicating. The high prevalence of self-medication indicates a need for education programs to increase awareness of risks.
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...iosrphr_editor
Aim: To study the clinico-haematological profile malaria in a rural hospital of Tripura.
Material and methods: A cross-sectional hospital-based study was done from at Kulai District
Hospital,Tripura. This hospital based cross sectional study was done on 60 confirmed cases of falciparum
malaria (either by peripheral smear or rapid diagnostic test) admitted in Kulai District Hospital. A case sheet
proforma was prepared and data (demographic profile,clinical feature, investigation, treatment, and
complication) from all indoor patients was collected and analyzed.
Result: Out of 60 patients, 40(66.6%) were males and 20 (33.4%) were females. Most of the patients were
between the age group 21-40 years with the highest prevalence between the age group of 21-30. Fever was the
most common symptom. Anemia was present in 42(70%) patients, out of which 6(10%) patients had severe
anemia. Thrombocytopenia was present in 36(60%) patients.Abnormal liver function tests were observed in
26(43.3%) subjects while abnormal kidney function tests were observed in16(26.6%) patients. All the 60
patients received Artemisinin based antimalarial drugs.
Conclusion: Early detection, prompt management, and adequate supportive therapy may reduce mortality due
to falciparum cerebral malaria.
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...iosrphr_editor
The document summarizes a study that tested the antibacterial activity of extracts from three species of wild ginger plants from Indonesia (Zingiber zerumbet, Zingiber amaricans, and Zingiber aromaticum) against Mycoplasma gallisepticum, a pathogen that causes respiratory disease in chickens. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, and terpenoids in the plant extracts. Disc diffusion and minimum inhibitory concentration assays showed that ethanol extracts of dried rhizomes had the strongest inhibitory effects against the pathogen, with minimum inhibitory concentrations ranging from 7.8 to 31.2 mg/ml. The results suggest that extracts from these wild ginger plants
A case of allergy and food sensitivity: the nasunin, natural color of eggplantiosrphr_editor
Abstract: Allergies and food sensitivities can both be considered as "adverse reactions individualistic" to food.
Are pathological and individual forms because they affect a few individuals in way rather serious; immediate
or delayed reactions occur instead with simple effects histamine, or, in severe cases with respiratory and
anaphylactic shock
The eggplant (Solanum melongena L.) is known to cause food allergies in some Asian countries, but detailed
studies on allergies caused by eggplant are lacking, however, it was highlighted the presence of allergens in
edible parts of eggplant with preponderance in the peel .
The purpose of this study was to propose an extraction method rapid, efficient and cost of natural dye from
waste products from the food industry, such as the peels of eggplant, from which it was extracted, isolated and
purified the nasunin,a colored molecule in red-fuchsia.
Nasusin was tested on 58 patients to evaluate the potential sensitizing effect on the skin. The results demonstrate
that allergenic effects are negligible and therefore the nasunin can be used as a colorant in various industrial
sectors with a certain safety margin
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...iosrphr_editor
NMR analysis allowed complete assignments of three known mogrol glycosides, Mogroside IIA2 (1),
II E (2)and IIIA1 (3), isolated from the extracts of Luo Han Guo. Herein, complete 1H and 13C NMR
assignmentsof all threemogrosidesare described based on NMR experiments (1H NMR, 13C NMR, COSY,
HSQC-DEPT, HMBC, NOESY and 1DTOCSY) and mass spectral data.
Nanoemulsion and Nanoemulgel as a Topical Formulationiosrphr_editor
: Nanoemulsion is referred type of emulsion with uniform and extremely small droplet size in the range
of 20-200 nm. Nanoemulsion provides numerous advantages over other carrier such as polymeric nanoparticle
and liposomes, including low cost preparation procedure, high hydrophilic and lipophilic drug loading system
to enhance the longer shelf live upon preserving the therapeutic agents. Incorporating the preparation of
nanoemulsion with hydrogel matrix to produce nanoemulgel exhibited by the two separate systems that forming
it. Nanoemulgel possesses the properties of thixotropic, non-greasy, effortlessly spreadable, easily be removed,
emollient, not staining, soluble in water, longer shelf life, bio-friendly, translucent and agreeable appearance.
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...iosrphr_editor
Aim:Since several factors have been shown to influence the clearance of methotrexate, the purpose of this study
was to identify potential relationships between patient covariates and the methotrexate clearance estimates and
deduce a pharmacokinetic model for the estimation of methotrexate clearance in Egyptian pediatric ALL
patients that may help dosage adjustment and achieve target steady-state plasma concentrations in a similar
sittings.
Patients and methods: A total of 94 pediatric patients with B-cell ALL, of whom 70 were the studied population
and 24 were the test population, were treated with four courses of HDMTX doses 2.5 gm/m2
(low-risk arm) or 5
gm/m2
(standard-/high-risk arm) given every other week by intermittent intravenous infusions over 24 hours as
a part of their treatment protocol. Patients were monitored for the 24 hour MTX concentration and the systemic
methotrexate clearance was calculated for each methotrexate dose
Epidemiology of Tuberculosis (TB) in Albania 1998-2009iosrphr_editor
Abstract : In Albania, many people erroneously think that tuberculosis (TB) is a disease of the past-an illness
that no longer constitutes a public health threat. Surveillance is an integral part of tuberculosis (TB) control.
Albania has a highTB notification rate and there are doubts about underreporting. The evolution of the
incidence of tuberculosis is presented, together with more detailed figures over the period 1998-2009. These
figures were obtained by the monthly forms (called 14/Sh) compared with the individual notification data.
Objective: To examine the distribution and sources of increased tuberculosis (TB) morbidity and reporting
system deficiencies in the Albania from 1998 through 2009. Metodology: The study is descriptive one conductet
during the period 1998-2009. The statistical analysis is based on data reported from regional level (regional
epidemiological departments) to the central level (Public Health Institute). Results: The main findings were:
discordance between the collected data (individual form) and reported data (monthly form); tuberculosis
incidence rate shows little oscillations which ranges from 6.67 to 9.2 cases/100.000 population; 50% of the
regions show a lack of information on the confirmation of diagnosis and laboratory examination type used for
confirmation. Conclusion: TB disease in high-risk populations where it is difficult to detect, diagnose, and treat;
limitations of current control measures and the need for new tests and treatments, including an effective
vaccine; improving information system, regulation of individual form and personnel training.
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...iosrphr_editor
Study on total phenol and antioxidantactivity ofsugar apple fruits of various solvent, part of fruits, and level of ripening. Solvent extraction used were 80% (v/v) methanol, 50% (v/v) acetone, boiling water, and 50% (v/v) ethanol. Part of fruits thatbeen used for samples were seed and peel which are normally by products of sugar apple processing, level of ripening were unripe, and ripe sugar apple fruits. Total phenol was determined by Folin-ciocalteau method. Total antioxidant was quantified by 1,1-diphenyl-2-picrylhydrazyl(DPPH) method.Therewas a difference in type of solvent, part of fruits, and level of ripeningon total phenol and antioxidant concentration of sugar apple fruits. Seeds have higher total phenol concentration than peels of this fruits. Unripe sugar apple fruits have higher total phenol and antioxidant than ripe fruit. The best solvent for phenol extraction was ethanol 50%butthe best solvent for antioxidant extraction was acetone 50%.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...iosrphr_editor
Non-steroidal anti-inflammatory drugs are the most widely used "over the counter" medication all over the world despite their complications in different major organs. Present studies envisaged for knowing the occurrence and severity of adverse drug reactions from NSAIDs in different ethnic communities of Sikkim. A cross sectional study was undertaken in the medicine outpatients department of a secondary and tertiary care hospital. The patients belonging to Nepalese, Bhutias, Lepchas ethnic communities and others community (settlers from other parts of India) were included to analyzed the data based on the age and gender, ethnicity and ADRs, drugs and ADRs. Severity assessment was done using Hartwing and Siegel scale and causality assessment by Naranjo scale. Total 109 cases of ADRs, predominating in female were detected. Nepalese were the most affected and Gastrointestinal tract (GIT) being the most affected organ in them. Diclofenac showed maximum number of ADRs in all the communities. Maximum number of cases occurred on single day use (40.36%) of drugs. All the cases were belonging to the "possible category" and the maximum being the mild (72.48%) in nature. It is advisable to consider the ethnic/racial differences equally with other factors, to improve the safety and efficacy of a drug.
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo
1. IOSR Journal of Pharmacy (IOSRPHR)
ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 62-68
www.iosrphr.org
Multidrug Resistant Tuberculosis; a Pharmacological view based
on Revised National Tuberculosis Control Programme
DOTS-Plus Guidelines.
Harminder Singh1*, Kamalpreet Kaur2, Girish P3
1-3
(Department of Pharmacology, Guru Gobind Singh, Medical College, Baba Farid University of Health
Sciences, Faridkot, Punjab.
Abstract––Directly Observed Therapy Strategy (DOTS) -Plus is a part of DOTS program that adds
approach for multidrug resistance tuberculosis (MDR-TB) diagnosis, management, and treatment. WHO
approved DOTS-Plus program began in 2000 and was established to encourage access to high quality
second line drugs for appropriate use in MDR-TB control programs. The top priority is to prevent the
emergence of MDR-TB by ensuring a low default rate of cases treated with first-line anti-TB drugs. If
MDR-TB has emerged in a certain area, it should be treated in addition to improving the basic treatment.
In this situation, accurate and reliable drug susceptibility testing, methods to support patients in order to
ensure direct observation of complete treatment and the use of maximally effective regimens must be
ensured. Second-line drugs should not be held back in patients with MDR-TB rather they have a good
chance of cure with it, hence the treatment, if it is to be provided, should be optimally selected and
administered. This review is highlighting the pharmacological view point of second line anti tubercular
drug incorporated in DOTS-Plus therapy for MDR-TB.
Keywords––DOTS-Plus therapy, DOTS, MDR-TB, Adverse drug reactions, Drug resistant
I. INTRODUCTION
Multidrug resistance tuberculosis is defined as a form of tuberculosis (TB) due to Mycobacterium (M)
tuberculosis that is resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. This form
of TB was documented in nearly every country surveyed by the World Health Organization.1, 2
With the implementation of the internationally accepted Directly Observed Therapy( DOTS) strategy
for TB control and its essential component of standardized short-course chemotherapy (SCC), a comprehensive
control strategy is available that, when followed properly, prevents the emergence of drug resistance. All
currently optional regimens are based upon the first-line drugs isoniazid, rifampicin, pyrazinamide, ethambutol
and streptomycin.3
Unfortunately, some of the same principles promoting resistance in patients in the 1950s remain intact
and prevalent today, in combination with other new factors: lack of adherence to treatment, use of low quality
drugs, improper diagnosis of TB patients, and lack of use of standard SCC.4
It is known that, MDR-TB patients are resistant to at least the two anchor drugs of SCC, a supplement
to the DOTS strategy is now needed for the management of these patients. This is further supported by evidence
showing that SCC offers cure rates of on average 52% and 29% in new MDR-TB patients and re-treatment
MDR-TB cases, respectively.5
To address MDR-TB in low- and middle-income settings, the World health organization (WHO) and
its partners created “DOTS- Plus for MDR-TB” a management strategy built upon the foundation and principles
of DOTS. The first WHO endorsed DOTS-Plus programmes began in 2000. At that time, the Green Light
Committee (GLC) was established to promote access to high quality second-line drugs for appropriate use in TB
control programmes.6
Magnitude of the MDR-TB problem in India
Data from studies conducted by Tuberculosis Research Centre (TRC) and National Tuberculosis
Institute (NTI), have found MDR-TB levels of less than 1% to 3% in new cases and around 12% in re-treatment
cases. 7, 8
Revised National Tuberculosis Control Programme (RNTCP) has recently undertaken two; community
based state level drug resistance surveillance (DRS) studies in Gujarat and Maharashtra. These surveys have
62
2. Multidrug Resistant Tuberculosis; a Pharmacological view based…..
been conducted as per a common generic protocol based on internationally accepted methodology and have
estimated the prevalence of MDR-TB to be about 3% in new cases and 12-17% in re-treatment case.9
Causes of drug-resistant tuberculosis
Table.1 summarizes the common causes of inadequate treatment. However it should be stressed that MDR-TB
is a man-made phenomenon – poor treatment, poor drugs and poor adherence lead to the development of MDR-
TB.4 (fig.1)
Table.1 Common causes of inadequate treatment
Providers/Programmes: Drugs: Patients:
Inadequate regimens Inadequate supply/quality Inadequate drug intake
-Absence of guidelines or -Non-availability of certain -Poor adherence (or poor
inappropriate guidelines drugs (Out of stock or delivery DOT)
-Non-compliance with disruptions) -Lack of information
guidelines -Poor quality -Non-availability of free drugs
-Inadequate training of health -Poor storage conditions -Adverse drug reactions
staff -Wrong dosages or -Social and economic barriers
-No monitoring of treatment combination -Malabsorption
-Poorly organized or funded -Substance abuse disorders
TB control programmes
Revised National Tuberculosis Control Programme, DOTS-Plus Guidelines FEB-2009
Fig.1 Acquired and primary resistance mechanism.
The RNTCP views the treatment of MDR-TB patients as a “standard of care” issue. Recognizing that
the treatment of MDR-TB cases is very complex, the treatment will follow the internationally recommended
DOTS-Plus guidelines and will be done in designated RNTCP DOTS-Plus sites.
63
3. Multidrug Resistant Tuberculosis; a Pharmacological view based…..
DOTS-PLUS: Category IV regimen for MDR-TB
RNTCP will be using a Standardized Treatment Regimen (Cat IV) for the treatment of MDR-TB cases
under the programme. Cat IV regimen comprises of 6 drugs (Kanamycin, Ofloxacin, Ethionamide,
Pyrazinamide, Ethambutol and Cycloserine) during 6-9 months of the Intensive Phase and 4 drugs (Ofloxacin,
Ethionamide, Ethambutol and Cycloserine) during the 18 months of the Continuation Phase. P-aminosalicylic
acid (PAS) is included in the regimen as a substitute drug if any bactericidal drug (Kanamycin, Ofloxacin,
Ethionamide and Pyrazinamide) or 2 bacteriostatic (Ethambutol and Cycloserine ) drugs are not tolerated .9
Table.2 DOTS compared to DOTS-Plus Strategy
DOTS DOTS-Plus
DOTS prevent emergence of drug resistant TB and DOTS –Plus design to cure MDR-TB using second
MDR-TB line drugs.
Make primarily use of 1 st line drugs that are less Make use of 2nd line drugs that are more toxic and
expensive. expensive, difficult to treat, less effective to
administrate and often poorly tolerated.
DOTS- Plus needed in area where MDR-TB has
emerged due to previous inadequate TB control.
DOTS-Plus only recommended in setting where
DOTS strategy is fully in place to prevent against the
development of further drug resistance.
Revised National Tuberculosis Control Programme, DOTS-Plus Guidelines FEB-2009
Drug dosages and administration
All drugs should be given in a single daily dosage under directly observed treatment (DOT) by a DOT
provider (Table.3). All patients will receive drugs under direct observation for 6 days of the week. On the 7th
day (Sunday) the oral drugs will be administered unsupervised whereas injection kanamycin will be omitted. If
intolerance occurs to the drugs, ethionamide, cycloserine and PAS may be split into two dosages and the
morning dose administered under DOT. The evening dose will be self-administered. The empty blister packs of
the self-administered doses will be checked the next morning during DOT. Pyridoxine at a dose of 100mg
should be administered to all patients on an RNTCP Category IV regimen.
Table.3 Dosage and weight band recommendations
Drugs 16-25 Kgs 26-45 Kgs >45 Kgs
Kanamycin 500 mg 500 mg 750 mg
Ofloxacin 400 mg 600 mg 800 mg
(Levofloxacin) (200 mg ) (500 mg ) (750 mg )
Ethionamide 375 mg 500 mg 750 mg
Ethambutol 400 mg 800 mg 1000 mg
Pyrazinamide 500 mg 1250 mg 1500 mg
Cycloserine 250 mg 500 mg 750 mg
PAS 5gm 10gm 12gm
Pyridoxine 50 mg 100 mg 100 mg
Revised National Tuberculosis Control Programme, DOTS-Plus Guidelines FEB-2009
Monitoring for early detection of adverse reactions
Close monitoring of patients is necessary to ensure that the adverse effects of Category IV anti-TB drugs
(DOTS-Plus regimens) are recognized early by the DOT provider (table.4).10 DOTS makes it possible to closely
monitor patients and addresses the following:
Monitoring for early detection of adverse reactions
Commonly encountered adverse reactions with second line drugs
Strategies for managing adverse reactions.
64
4. Multidrug Resistant Tuberculosis; a Pharmacological view based…..
Table.4 Common adverse reactions to the drugs used
Kanamycin (Aminoglycosides) 11,12 Ototoxicity, nephrotoxicity, vertigo, electrolyte imbalance.
Ofloxacin (Quinolones)13,14 Gastro intestinal symptoms: diarrhea, vomiting, and abdominal pain,
central nervous system (CNS): dizziness and convulsions,
phototoxicity and photosensitivity, tendinopathy and tendinitis
nephrotoxicity skin rash cardiotoxicity arthralgia
Ethambutol Visual disturbance
Pyrazinamide Arthralgia , hyperuricaemia , hepatitis,
pruritis with or without rash
Ethionamide Gastro-intestinal: epigastric discomfort, anorexia, nausea, metallic
taste, vomiting, excessive salivation, and sulfurous belching
psychiatric: hallucination and depression ,hepatitis ,hypothyroidism
and goitre with prolonged administration, gynaecomastia, menstrual
disturbances, impotence, acne, headache, and peripheral neuropathy
Cycloserine. 15 CNS: dizziness, slurred speech, convulsions, headache, tremor, and
insomnia , psychiatric: confusion, depression, altered behaviour, and
suicidal tendency, hypersensitivity reaction
PAS Gastro-intestinal: anorexia, nausea, vomiting, and abdominal
discomfort, skin rash, hepatic dysfunction
hypokalemia, hypothyroidism and goitre with prolonged
administration.
Revised National Tuberculosis Control Programme, DOTS-Plus Guidelines FEB-2009
Adverse effects, suspected drugs, and management strategies
Gastro-intestinal symptoms (nausea and vomiting): This may be due to the bulk of drugs and/or due to
ethionamide, PAS, pyrazinamide and ethambutol. Patients who complain of nausea or vomiting can be advised
to take the drugs embedded in a banana. If vomiting persists, drugs will be administered one hour after one
tablet of domperidone and/or a course of proton pump inhibitor or H2 receptor inhibitor (omeprazole,
famotidine, ranitidine).
Giddiness: Giddiness could be due to aminoglycosides, ethionamide, quinolone and/or pyrazinamide.
Whenever a patient complains of giddiness, over sleepiness or poor concentration, patients need to be
counseled.
Ocular toxicity: Whenever a patient complains of blurring of vision or disturbance in colour vision, ethambutol
should be withheld.
Renal toxicity: Common offending drug is an aminoglycoside. During treatment, blood urea and serum
creatinine should be done every month for the first three months after treatment initiation and then every three
months thereafter whilst injection kanamycin is being administered.
Arthralgia: The offending drugs are likely to be pyrazinamide and/or quinolones. Patients who complain of
arthralgia will be prescribed paracetamol 500mg three times a day or aspirin 300mg three times a day. If there is
no improvement after one week, a non-steroidal anti-inflammatory drug will be prescribed (e.g. ibuprofen
200mg three times a day).
Cutaneous reactions: If there is a generalized erythematous rash, especially if it is associated with fever and/or
mucous membrane involvement, all drugs should be withheld immediately. When the rashes subside, the
medications can be restarted one by one, at intervals of 2-3 days. The order of reintroduction will be ethambutol,
cycloserine, ethionamide, quinolones, kanamycin and lastly pyrazinamide.
Hepatitis: This could be due to the combined effect of potentially hepatotoxic drugs such as pyrazinamide and
ethionamide. If the liver function test results are abnormal ethionamide and pyrazinamide are to be withheld,
and the other drugs continued.
Neurological symptoms: In case of peripheral neuropathy the common offending drugs are cycloserine and
ethionamide. To prevent the occurrence of such adverse reaction, all patients on an RNTCP Category IV
regimen should receive daily pyridoxine 100mg. If peripheral neuropathy develops, an additional 100mg
pyridoxine will be given. In case of seizures the offending drug could be either quinolones and/or cycloserine. If
a patient develops seizures these drugs will be withheld and the patient will be referred to a neurologist for
opinion.
Psychiatric disturbances: The common offending drugs are cycloserine, quinolones and/or ethionamide. In
cases of suicidal tendencies and other psychiatric disturbances, the first offending drug is cycloserine, followed
65
5. Multidrug Resistant Tuberculosis; a Pharmacological view based…..
by ethionamide and quinolones. These drugs will be withheld and further management of the patient will be
done in consultation with the psychiatrist. 16
Vestibulo-auditory disturbances: Offending drug is usually the aminoglycosides. Patient may present with
tinnitus, unsteady gait or loss of hearing. Aminoglycoside will be withheld and patient referred for a specialist
opinion.
Hypothyroidism: The offending drugs are usually PAS and/or ethionamide and the combination of these drugs
may increase the possibility for the same. Patients may present with slowing of activities, puffiness of face
and/or thyroid swelling. Patients need to be evaluated for hypothyroidism and if present, may be treated with
thyroxin.
MDR-TB in special situations
DOTS-Plus (MDR-TB) in pregnancy: teratogenicity has been demonstrated in only a few of the drugs used to
treat MDR-TB, all except ethambutol have uncertain safety information available. This all makes treating MDR-
TB during pregnancy very challenging
All women of childbearing age who are receiving MDR-TB therapy should be advised to use birth
control measures because of the potential consequences for both mother and fetus resulting from frequent and
severe adverse drug reactions. It should be remembered that oral contraceptives might have decreased efficacy
due to vomiting and drug interactions with MDR-TB drugs. 17,18,19
MDR-TB with HIV co-infection
The treatment of HIV positive individual with MDR-TB is the same as for HIV negative patients. However
treatment is more difficult and adverse events more common. (table.5)
Table.5 DOTS-Plus regimen’s Interaction potential with antiretroviral drugs:
DOTS-Plus Protease inhibitor NNRTIs NRTIs
regimen’s drug
classes
Aminoglycosides Interactions unlikely. Use Interactions unlikely Use standard Interactions unlikely Use
standard doses but monitor doses but monitor renal function standard doses but monitor
renal function. renal function
Thioamides: Risk of hepatoxicity with Risk of hepatoxicity with No studies have been
tipranavir Efavirenz and nevirapine. performed, interactions
and darunavir. difficult to predict.
Cycloserine No studies have been Monitor for psychiatric morbidity No studies have been
performed with efavirenz. performed
Fluoroquinolone Interactions with ofoxacin, Cause prolongation of the QT Oral absorption is reduced
levofoxacin or gatifoxacin interval and should be used with by buffered drugs.No
Are not predicted. caution with other agents that do studies have been
Cause prolongation of the the same, including efavirenz.21 performed, interactions
QT interval and should be difficult to predict.
used with caution with
other agents that do the
same, including PIs.20
PAS: No studies have been No studies have been performed No studies have been
performed but interactions But interactions unlikely. performed
unlikely. But interactions unlikely.
NNRTIs, non nucleoside reverse transcriptase inhibitors; NRTIs, nucleoside reverse transcriptase
inhibitors; PI, protease inhibitor. Other possible reinforcing drugs (Third line drugs)
Amoxicillin with clavulanic acid: Beta-Lactam antibiotics have had a very limited role in the treatment of TB
because mycobacteria produce beta-lactamase. Amoxicillin with clavulanic acid has been used at high doses in
multi drug regimens against TB with some success. 22 Amoxicillin is commonly used in individuals with HIV
infection and interactions with antiretroviral are unlikely. The addition of a beta-lactamase inhibitor to
amoxicillin greatly improves its in vitro activity against M. tuberculosis. 23
Clarithromycin: a semi-synthetic, second generation macrolide, clarithromycin, is effective against
Mycobacterium avium-complex, and other NTM (Non-tubercular mycobacteria) including M. para tuberculosis.
It is also recommended in the treatment of infections caused by Mycobacterium marinum and Mycobacterium
66
6. Multidrug Resistant Tuberculosis; a Pharmacological view based…..
fortuitum complex. It has been shown to cause a reduction in the bacillary load and clinical improvement of M.
avium disease in AIDS patients. When administered orally it undergoes first- pass metabolism so that the
bioavailability is 55%. It can also be given intravenously. Interactions between Clarithromycin and several
antiretroviral have been studied. Simultaneous co-administration of Clarithromycin reduces zidovudine
concentrations, but no reduction is seen if Clarithromycin and zidovudine are given at least 2hrs apart. 24
Linezolid : Linezolid is a new synthetic antibacterial agent of the oxazolidinone class, which has recently been
used in Successful regimens against MDR-TB.25 However, long term toxicities are concerning. Linezolid can
cause reversible myelosuppression 26,27 and should be used cautiously in patients with preexisting cytopaenias,
including those with anemia on zidovudine. Prolonged courses of linezolid have been associated with lactic
acidosis and optic or peripheral neuropathy and appear to inhibit mitochondrial protein synthesis. 28,29,30 It
would therefore be advisable not to co-administer other drugs, which suppress mitochondrial activity such as
didanosine, stavudine, and to a lesser extent zidovudine.
Clofazimine: Clofazimine is a substituted iminophenazine bright-red dye that inhibits mycobacterial growth
and binds preferentially to mycobacterial DNA causing inhibition of transcription. The MlCs of clofazimine
against M. tuberculosis have not been published. Adverse reactions include discoloration of the skin,
gastrointestinal upset, severe and life-threatening abdominal pain and organ damage caused by clofazimine
crystal deposition, and asymptomatic discoloration of the eye. 31, 32
Amikacin: Amikacin, an aminoglycoside, is highly bactericidal against M. tuberculosis. It is given five days a
week in a dose of 15 mg/kg/day as a single dose, usually by intramuscular injection. The major side effect of
amikacin is nephrotoxicity and vestibular damage. Hearing loss, hypocalcaemia, hypokalaemia and
hypomagnesaemia are other side effects. In comparison to kanamycin, it is less ototoxic and less painful. 33
Capreomycin: Capreomycin is an aminoglycoside which is bactericidal against M. tuberculosis. It is given in a
dose of 15 mg/kg/day intramuscularly with maximum of 1 Gram. It is toxic to the eighth cranial nerve, causing
high frequency hearing loss in 3.2 to 9.4% of patients before vestibular dysfunction occurs. Renal toxicity is
somewhat more common with capreomycin than with streptomycin, and it may be associated with electrolyte
disturbances secondary to tubular damage. It is suggested that in elderly patients when there is similar
susceptibility to capreomycin and amikacin, capreomycin should be used since older patients seem to experience
more renal and ototoxic effects with amikacin than with capreomycin.33
II. CONCLUSION
DOTS is a established cost-effective TB treatment strategy. A blend of technical and managerial
components, DOTS quickly makes infectious cases non-infectious and breaks the cycle of transmission. Using
DOTS also prevents the development of drug-resistant strains of TB that are often fatal and very expensive to
cure.34Multi-drug-resistant TB is both an individual misfortune and a manifestation of poor program
performance. The top priority is to prevent the emergence of MDR-TB by ensuring a low default rate of cases
treated with first-line anti-TB drugs. If MDR-TB has emerged in a certain area, it should be treated in addition
to improving the basic treatment. In this situation, accurate and reliable dug susceptibility testing, methods to
support patients in order to ensure direct observation of complete treatment, and the use of maximally effective
regimens must be ensured. Patients with MDR-TB have a good chance for a cure with second-line drugs, hence
the treatment, if it is to be provided, should be optimally selected and administered.35 Second-line drugs should
not be kept in reserve and the treatment observation must be ensured.
Second-line TB drugs include in DOTS-Plus strategy are characterized by varied metabolic pathways.
Some of these are among the oldest antimicrobials introduced into clinical practice, others have been newly
approved.
Pharmacology of second-line TB drugs is elementary to managing MDR-TB in the shadow of
escalating HIV epidemic especially where patients are intolerant of first-line TB drugs. MDR-TB is emerging
epidemic and its management is challenging. Further needs to be done in resource-poor settings, in which the
burden of HIV/ TB co-infection is greatest. The burden of MDR-TB can be reduced by better implementation of
DOTS to rapidly identify, trace and re-instate treatment in poorly adherent patients receiving first-line TB drugs.
So even though we have DOTS-Plus (second line TB drugs) the crucial element of whole strategy is to
strengthening of DOTS (first line TB drugs) to preclude emergence of MDR-TB.
67
7. Multidrug Resistant Tuberculosis; a Pharmacological view based…..
REFERENCES
[1]. Pablos-Méndez A, Raviglione MC, Laszlo A, et al. Global surveillance for antituberculosis drug resistance, 1994-1997. N Engl J
Med 1998;338:1641-49.
[2]. Espinal MA, Laszlo A, Simonsen L, et al. Global trends in resistance to antituberculosis drugs. N Engl J Med 2001;344:1294-
1303.
[3]. World Health Organization. Treatment of tuberculosis (rev 3). WHO/CDS/TB/2003.313. Geneva: WHO, 2003.
[4]. Lambregts-van Weezenbeek C S B, Veen J. Control of drug- resistant tuberculosis. Tubercle Lung Dis 1995; 76: 455-459.
[5]. Espinal MA, Kim SJ, Suarez PG, et al. Standard short-course chemotherapy for drug-resistant tuberculosis; treatment out- comes
in six countries. JAMA 2000;283:2537-45.
[6]. World Health Organization. DOTS-Plus: preliminary results and emerging issues. Proceedings of the Meeting of the Stop TB
Working Group on DOTS-Plus for MDR-TB. Tallinn, Estonia. 10-12 April 2002. WHO/CDS/TB/2002.307. Geneva: WHO,
2002.
[7]. Mahadev B, Kumar P, Agarwal SP, Chauhan LS, Srikantaramu N. Surveillance of drug resistance to anti-tuberculosis drugs in
districts of Hoogli in West Bengal and Mayurbhanj in Orissa. Indian J Tuberc 2005:52;5-10.
[8]. Paramasivan CN, Venkataraman P, Chandrasekaran V, Bhat S,Narayanan PR. Surveillance of drug resistance in tuberculosis in
two districts of South India. Int J Tuberc Lung Dis 2002:6;479-484.
[9]. Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare. DOTS-Plus Guidelines FEB-
2009. Nirman Bhavan, New Delhi: Revised National Tuberculosis Control Programme. p. 39-54.
[10]. Furin JJ, Mitnick CD, Shin SS et al. Occurrence of serious adverse effects in patients receiving community-based therapy for
multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2001;5:648-55.
[11]. Moore RD, Smith CR, Lietman PS. Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J
Infect Dis 1984;149:23–30.
[12]. de Jager P, van Altena R. Hearing loss and nephrotoxicity in long-term aminoglycoside treatment in patients with tuberculosis.
Int J Tuberc Lung Dis 2002;6:622–27.
[13]. Arora VK, Tumbanatham A. Severe arthropathy with ofloxacin in two cases of MDR tuberculosis. Int J Tuberc Lung Dis
1998;2:941-3.
[14]. Yew WW, Chan CK, Chau CH, et al. Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with
ofloxacin/levofloxacin containing regimens. Chest 2000;117:744–51.
[15]. Akula SK, Aruna AS, et al. Cycloserine-induced Stevens-Johnson syndrome in an AIDS patient with multidrug- resistant
tuberculosis. Int J Tuberc Lung Dis 1997;1:187-90.
[16]. Vega P, Sweetland A, Acha J, et al. Psychiatric issues in the management of patients with multidrug-resistant tuberculosis. Int J
Tuberc Lung Dis 2004;8:749–758.
[17]. Drobac PC, del Castillo H, Sweetland A, Anca G, Joseph JK, Furin J, Shin S. Treatment of multidrug-resistant tuberculosis
during pregnancy: long-term follow-up of 6 children with intrauterine exposure to second-line agents. Clin Infect Dis
2005;40:1689-92.
[18]. Shin S, Guerra D, Rich M, Seung KJ, Mukherjee J, Joseph K, Hurtado R, Alcantara F, Bayona J, Bonilla C, Farmer P, Furin J.
Treatment of multidrug-resistant tuberculosis during pregnancy: a report of 7 cases. Clin Infect Dis 2003;36:996-1003.
[19]. Duff P. Antibiotic selection in obstetric patients. Infect Dis Clin North Am.1997;11:1-12.
[20]. Anson BD,Weaver JG, Ackerman MJ, Akinsete O, Henry K, January CT, et al. Blockade of HERG channels by HIV protease
inhibitors. Lancet 2005;365:682–86.
[21]. Castillo R, Pedalino RP, El-Sherif N, Turitto G. Efavirenz-assoCiated QT prolongation and torsade de pointes arrhythmia. Ann
Pharmacother 2002;36:1006–8.
[22]. Nadler JP, Berger J, Nord JA, Cofsky R, Saxena M. Amoxicillin-clavulanic acid for treating drug-resistanct Mycobacterium
tuberculosis. Chest 1991;99:1025-26.
[23]. Wong CS, Palmer GS, Cynamon MH. In vitro susceptibility of Mycobacterium tuberculsis, Mycobacterium bovis and
Mycobacterium kansasii to amoxycillin and ticarcillin in combination with clavulanic acid. J Antimicrob Chemother
1968;22:663-6.
[24]. Polis MA, Piscitelli SC, Vogel S,Witebsky FG,Conville PS, Petty B, et al. Clarithromycin lowers plasma zidovudine levels In
persons with human immuno deficiency virus infection. Antimicrob Agents Chemother 1997;41:1709-14.
[25]. Fortún J, Martín-Dávila P, Navas E, Pérez-Elías MJ, Cobo J, Tato M, et al. Linezolid for the treatment of multidrug Resistant
tuberculosis. J Antimicrob Chemother 2005;56:180-5.
[26]. Green SL, Maddox JC, Huttenbach ED. Linezolid and reversible myelosuppression. JAMA 2001;285:1291.
[27]. Bishop E, Melvani S, Howden BP, Charles PG, Grayson ML. Good clinical outcomes but high rates of adverse reactions During
linezolid therapy for serious infections: a proposed Protocol for monitoring therapy in complex patients. Antimicrob Agents
Chemother 2006;50:1599-1602.
[28]. De Vriese AS, Coster RV, Smet J, Seneca S, Lovering A, Van Haute LL, et al. Linezolid –induced inhibition of mitochondrial
protein synthesis. Clin Infect Dis 2006;42:1111-17.
[29]. Garrabou G, Soriano A, López S, Guallar JP, Giralt M, Villarroya F, et al. Reversible inhibition of mitochondrial protein
synthesis during linezolid-related hyperlactatemia. Antimicrob Agents Chemother 2007;51:962-67.
[30]. Rubinstein E, Isturiz R, Standiford HC, Smith LG, Oliphant TH, Cammarata S, et al. Worldwide assessment of linezolidís
clinical safety and tolerability: comparator-controlled phase III studies. Antimicrob Agents Chemother 2003;47:1824-31.
[31]. Arbiser JL, Moschella SL.Clofazimine: are view of its medical Uses and mechanisms of action. J Am Acad Dermatol
1995;32:241-47.
[32]. Holdiness MR. Clinical pharmacokinetics of clofazimine: a review. Clin Pharmacokinet 1989; 16:74–85.
[33]. HoYI,Chan CY,Cheng AF. In-vitro activities of aminoglycoside-aminocyclitols against mycobacteria. J Antimicrob Chemother
1997; 40:27–32.
[34]. WHO, Geneva, Switzerland. What is DOTS? A guide to understanding the WHO recommended TB control strategy known as
DOTS 1999; WHO/CDS/CPC/TB/99.270:5
[35]. Frieden TR, Khatri GR. Multi Drug Resistant Tuberculosis In: Tuberculosis, Epidemiology and Control, Vol. 1. New Delhi:
WHO, Regional Office for South East Asia; p. 105-15.
68