Chemotherapy uses chemical agents to treat diseases like infections and cancer. There are different types of chemotherapeutic agents that target different microorganisms and cancerous cells. Antibiotics are a major type of chemotherapeutic agent used to treat bacterial infections. For antibiotics to be clinically useful, they must selectively kill pathogens without harming the host and must reach the site of infection at effective concentrations. However, achieving this selectivity is complex and depends on interactions between the patient, drug, and pathogen.
This document discusses control of microorganisms through antimicrobial agents. It defines chemotherapy and antimicrobials, and notes that antibiotics are a type of antimicrobial. It describes how antimicrobial drugs work by exploiting biochemical differences between microbes and humans. It discusses the spectrum of antibiotic activity, mechanisms of antimicrobial action including inhibition of cell wall synthesis and protein synthesis, and selection of antimicrobial agents based on the organism, site of infection, and patient factors. Mechanisms of resistance and factors promoting resistance are also summarized.
The document discusses general principles of antimicrobial therapy and chemotherapy of infectious diseases. It covers topics such as the ideal properties of antimicrobial drugs, mechanisms of bacterial resistance, principles of antimicrobial selection and combination therapy. It also discusses appropriate and misuse of antimicrobial agents, highlighting the importance of judicious antibiotic use to prevent resistance.
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It covers their sources, mechanisms of action, spectrum of activity, types of action (bacteriostatic vs bactericidal), resistance to antibiotics, and prevention of drug resistance. The key topics covered are the different classes of antimicrobial agents, how they work to suppress microbes, developing resistance in bacteria, and the importance of responsible antibiotic use to prevent further resistance.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It covers their sources, mechanisms of action, spectrum of activity, types of action (bacteriostatic vs bactericidal), resistance to antibiotics, and prevention of drug resistance. The key topics covered are the different classes of antimicrobial agents, how they work to suppress microbes, developing resistance in bacteria, and the importance of responsible antibiotic use to prevent resistance.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It covers their sources, mechanisms of action, spectrum of activity, types of action (bacteriostatic vs bactericidal), resistance to antibiotics, and prevention of drug resistance. The key topics covered are the different classes of antimicrobial agents, how they work to suppress microbes, developing resistance in bacteria, and the importance of responsible antibiotic use to prevent further resistance.
GENERAL PRINCIPLES OF ANTIBIOTIC THERAPY.pptxShaanSinojia
To review about general principles of antibiotic therapy to understand more about their action and precautions while prescribing antibiotics to the patient.
This document discusses control of microorganisms through antimicrobial agents. It defines chemotherapy and antimicrobials, and notes that antibiotics are a type of antimicrobial. It describes how antimicrobial drugs work by exploiting biochemical differences between microbes and humans. It discusses the spectrum of antibiotic activity, mechanisms of antimicrobial action including inhibition of cell wall synthesis and protein synthesis, and selection of antimicrobial agents based on the organism, site of infection, and patient factors. Mechanisms of resistance and factors promoting resistance are also summarized.
The document discusses general principles of antimicrobial therapy and chemotherapy of infectious diseases. It covers topics such as the ideal properties of antimicrobial drugs, mechanisms of bacterial resistance, principles of antimicrobial selection and combination therapy. It also discusses appropriate and misuse of antimicrobial agents, highlighting the importance of judicious antibiotic use to prevent resistance.
There are many ways that drug-resistant infections can be prevented: immunization, safe food preparation, handwashing, and using antibiotics as directed and only when necessary. In addition, preventing infections also prevents the spread of resistant bacteria.The main cause of antibiotic resistance is antibiotic use. When we use antibiotics, some bacteria die but resistant bacteria can survive and even multiply. The overuse of antibiotics makes resistant bacteria more common. The more we use antibiotics, the more chances bacteria have to become resistant to them.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It covers their sources, mechanisms of action, spectrum of activity, types of action (bacteriostatic vs bactericidal), resistance to antibiotics, and prevention of drug resistance. The key topics covered are the different classes of antimicrobial agents, how they work to suppress microbes, developing resistance in bacteria, and the importance of responsible antibiotic use to prevent further resistance.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It covers their sources, mechanisms of action, spectrum of activity, types of action (bacteriostatic vs bactericidal), resistance to antibiotics, and prevention of drug resistance. The key topics covered are the different classes of antimicrobial agents, how they work to suppress microbes, developing resistance in bacteria, and the importance of responsible antibiotic use to prevent resistance.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It covers their sources, mechanisms of action, spectrum of activity, types of action (bacteriostatic vs bactericidal), resistance to antibiotics, and prevention of drug resistance. The key topics covered are the different classes of antimicrobial agents, how they work to suppress microbes, developing resistance in bacteria, and the importance of responsible antibiotic use to prevent further resistance.
GENERAL PRINCIPLES OF ANTIBIOTIC THERAPY.pptxShaanSinojia
To review about general principles of antibiotic therapy to understand more about their action and precautions while prescribing antibiotics to the patient.
This document discusses antimicrobial agents and chemotherapy. It begins by defining antibiotics as natural substances produced by microorganisms that suppress or kill other microorganisms. It then discusses antimicrobial agents, which include both naturally obtained and synthetic drugs that can attenuate microorganisms. Finally, it defines chemotherapeutic agents as drugs designed to inhibit or kill an infecting organism with minimal effect on the recipient. The document goes on to provide details on the classification, mechanisms, principles, development and prevention of antimicrobial resistance.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It defines these terms and describes the sources, mechanisms of action, types of action (bacteriostatic vs bactericidal), spectrum of activity, and resistance of antimicrobial agents. It emphasizes the importance of responsible antibiotic use to prevent further development of antibiotic resistance which threatens the end of the antibiotic era.
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
This document provides an overview of antibiotics, including their classification, mechanisms of action, and common types. It discusses how antibiotics are classified based on their mechanism of action, spectrum of activity, and mode of action. The major classes covered include penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. Specific antibiotics are given within each class with details on their indications, mechanisms, and side effects. Combination antibiotic therapy and developing antibiotic resistance are also summarized.
This document provides an overview of different classes of antibiotics, including their mechanisms of action, common uses, and side effects. It discusses penicillins, cephalosporins, carbapenems, monobactams, macrolides, ketolides, lincosamides, aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. It also covers topics like antibiotic resistance, combinations, ideal properties, and complications of antibiotic therapy.
This document provides an overview of antibiotics, including their classification, mechanisms of action, and common types. It discusses how antibiotics are classified based on their mechanism of action, spectrum of activity, and mode of action. The major classes covered include penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. Specific antibiotics are given within each class with details on their indications, mechanisms, and side effects. Combination antibiotic therapy and developing antibiotic resistance are also summarized.
This document summarizes chemotherapy and antibiotic resistance. It discusses:
- The development of chemotherapy from the 1850s onward, including the discovery of sulfa drugs, penicillin, and streptomycin.
- How chemotherapeutic agents work, including their therapeutic index and mechanisms of action. Common classes of antimicrobial drugs like sulfa drugs, penicillin, and cephalosporins are described.
- How bacteria develop resistance to antibiotics through mechanisms like preventing drug entry, pumping drugs out, and enzymatically inactivating drugs. Genetic mutations also allow bacteria to evade antibiotics.
This document provides information on chemotherapeutic drugs and antimicrobial mechanisms of action and resistance. It begins by outlining the learning objectives which are to describe the principles of chemotherapy, mechanisms of antimicrobial drug action and resistance, specific drug classes and their effects. It then discusses the basic principles of chemotherapy and antimicrobials before explaining various mechanisms of antimicrobial action and how selective toxicity is achieved. The document closes by discussing antimicrobial resistance and complications of drug therapy.
The document provides an overview of antibiotic resistance, including definitions of antibiotics and antibiotic resistance. It discusses mechanisms of antibiotic resistance such as enzyme modification, altered target sites, efflux pumps, and decreased membrane permeability. Causes of resistance include overuse and misuse of antibiotics in humans, agriculture, and health care settings. Management of resistance involves prudent antibiotic use, infection control, developing new antibiotics, and global cooperation. National action plans aim to combat resistance through improved awareness, surveillance, optimal antibiotic use, and investments in research.
The document summarizes a group presentation on antibiotic resistance. It begins with an introduction that defines antibiotic resistance and outlines the presentation topics. These include a brief history of antibiotics, factors contributing to resistance, examples of resistant bacteria, and mechanisms of resistance. It then discusses the concerns of physicians regarding resistant infections and strategies for managing resistance, such as prudent antibiotic use, development of new drugs, and controlling spread. It concludes that human overuse of antibiotics has led to widespread resistance and that improved hygiene and isolation can help control spread.
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.
antibiotics are necessary to treat infections and chemotherapeutic agents are also used for this purpose. Chemotherapeutic agents are also used in the treatment of cancers. These therapeutic agents have limitations, specific action and a set mode of action. We can say that they are selective. The antibiotics are natural as well as synthetic in nature and have specificity for action against the microorganisms. Chemotherapeutic agents are chemical in nature and are synthesised in labs. They are less selective in action.
The document provides an overview of pharmacology of antimicrobials including:
1. It classifies antimicrobials by the microorganism they affect such as antibacterial, antifungal, and antiviral drugs.
2. It discusses important concepts such as bacteriocidal vs. bacteriostatic effects, selective toxicity, and organism sensitivity.
3. It covers antimicrobial resistance including common mechanisms and factors that promote development of resistance.
Antimicrobial agents work by interfering with essential processes in microorganisms like bacteria, fungi and parasites. They are commonly used to treat infections caused by these microorganisms. There are several classes of antimicrobial agents classified based on their chemical structure and mechanisms of action. Some common mechanisms include inhibiting cell wall synthesis, disrupting cell membranes, and inhibiting protein or nucleic acid synthesis. Microorganisms can develop resistance to antimicrobial agents through various mechanisms such as enzymatic modification, target site alterations, and efflux pumps. Antibiotic sensitivity testing helps determine the most effective antibiotic for treating a bacterial infection.
What are antibiotics? How do antibiotics work? Antibiotic Mode Of Action. DETERMINANTS OF RATIONAL DOSING. CHEMOTHERAPEUTIC SPECTRA , Principles of Antibiotic Therapy .Empirical Antibiotic Therapy , Factors Influencing Antibiotic Choice. Prophylaxis for Selected Types of Surgery
This document provides an overview of basic principles of antimicrobial therapy. It discusses key terms like antimicrobial, pharmacodynamics, pharmacokinetics and selective toxicity. It also covers topics like antibiotic resistance, restricted antibiotics, selection of antibiotics, antibiotic combinations, classification of antimicrobials by category and common drugs and their indications and adverse drug reactions. The document serves as a comprehensive reference on fundamental concepts in antimicrobial treatment and management.
This document discusses antibiotics, including their classification, mechanisms of action, uses, and side effects. It covers several classes of antibiotics such as penicillins, cephalosporins, and their generations. Antibiotics work by inhibiting bacterial cell wall synthesis, disrupting cellular membranes, or interfering with protein, nucleic acid, or folic acid synthesis. Their use requires consideration of the infecting organism, patient factors, and development of resistance. Combination antibiotic therapy can have additive, synergistic, or antagonistic effects.
Rational Use of Antibiotics. Infection was a major cause of morbidity and mortality, before the development of antibiotics.
The treatment of infections faced a great challenge during those periods.
Later in 1928, the discovery of Penicillin, a beta-lactam antibiotic, by Alexander Fleming opened up the golden era of antibiotics.
It marked a revolution in the treatment of infectious diseases and stimulated new efforts to synthesize newer antibiotics.
The period between the 1950s and 1970s is considered the golden era of discovery of novel antibiotic classes, with very few classes discovered since then.
Antibiotic resistance occurs when bacteria change in response to antibiotic use, making infections harder to treat. Bacteria, not humans or animals, become resistant. This leads to higher medical costs, prolonged hospital stays, and increased deaths. Antibiotic resistance threatens global health and can affect anyone, of any age, in any country. It occurs naturally but also because of misuse of antibiotics in humans and farm animals. This is making many infections like pneumonia, tuberculosis, and gonorrhea more difficult to treat.
Principles of antimicrobial therapy - PharmacologyAreej Abu Hanieh
This document discusses antimicrobial therapy and antibiotic selection and use. It provides information on:
- How antimicrobials target biochemical differences between microbes and humans
- Factors to consider when selecting an antibiotic, including the microbe, site of infection, and patient factors
- How bacteriostatic and bactericidal drugs work differently
- Key concepts regarding pharmacodynamics and pharmacokinetics of antimicrobial drugs
- Common classes of antibiotics like penicillins, cephalosporins, aminoglycosides and their mechanisms of action
This document discusses antimicrobial agents and chemotherapy. It begins by defining antibiotics as natural substances produced by microorganisms that suppress or kill other microorganisms. It then discusses antimicrobial agents, which include both naturally obtained and synthetic drugs that can attenuate microorganisms. Finally, it defines chemotherapeutic agents as drugs designed to inhibit or kill an infecting organism with minimal effect on the recipient. The document goes on to provide details on the classification, mechanisms, principles, development and prevention of antimicrobial resistance.
This document discusses antimicrobial agents including antibiotics, antimicrobial agents, and chemotherapeutic agents. It defines these terms and describes the sources, mechanisms of action, types of action (bacteriostatic vs bactericidal), spectrum of activity, and resistance of antimicrobial agents. It emphasizes the importance of responsible antibiotic use to prevent further development of antibiotic resistance which threatens the end of the antibiotic era.
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
This document provides an overview of antibiotics, including their classification, mechanisms of action, and common types. It discusses how antibiotics are classified based on their mechanism of action, spectrum of activity, and mode of action. The major classes covered include penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. Specific antibiotics are given within each class with details on their indications, mechanisms, and side effects. Combination antibiotic therapy and developing antibiotic resistance are also summarized.
This document provides an overview of different classes of antibiotics, including their mechanisms of action, common uses, and side effects. It discusses penicillins, cephalosporins, carbapenems, monobactams, macrolides, ketolides, lincosamides, aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. It also covers topics like antibiotic resistance, combinations, ideal properties, and complications of antibiotic therapy.
This document provides an overview of antibiotics, including their classification, mechanisms of action, and common types. It discusses how antibiotics are classified based on their mechanism of action, spectrum of activity, and mode of action. The major classes covered include penicillins, cephalosporins, macrolides, aminoglycosides, fluoroquinolones, and tetracyclines. Specific antibiotics are given within each class with details on their indications, mechanisms, and side effects. Combination antibiotic therapy and developing antibiotic resistance are also summarized.
This document summarizes chemotherapy and antibiotic resistance. It discusses:
- The development of chemotherapy from the 1850s onward, including the discovery of sulfa drugs, penicillin, and streptomycin.
- How chemotherapeutic agents work, including their therapeutic index and mechanisms of action. Common classes of antimicrobial drugs like sulfa drugs, penicillin, and cephalosporins are described.
- How bacteria develop resistance to antibiotics through mechanisms like preventing drug entry, pumping drugs out, and enzymatically inactivating drugs. Genetic mutations also allow bacteria to evade antibiotics.
This document provides information on chemotherapeutic drugs and antimicrobial mechanisms of action and resistance. It begins by outlining the learning objectives which are to describe the principles of chemotherapy, mechanisms of antimicrobial drug action and resistance, specific drug classes and their effects. It then discusses the basic principles of chemotherapy and antimicrobials before explaining various mechanisms of antimicrobial action and how selective toxicity is achieved. The document closes by discussing antimicrobial resistance and complications of drug therapy.
The document provides an overview of antibiotic resistance, including definitions of antibiotics and antibiotic resistance. It discusses mechanisms of antibiotic resistance such as enzyme modification, altered target sites, efflux pumps, and decreased membrane permeability. Causes of resistance include overuse and misuse of antibiotics in humans, agriculture, and health care settings. Management of resistance involves prudent antibiotic use, infection control, developing new antibiotics, and global cooperation. National action plans aim to combat resistance through improved awareness, surveillance, optimal antibiotic use, and investments in research.
The document summarizes a group presentation on antibiotic resistance. It begins with an introduction that defines antibiotic resistance and outlines the presentation topics. These include a brief history of antibiotics, factors contributing to resistance, examples of resistant bacteria, and mechanisms of resistance. It then discusses the concerns of physicians regarding resistant infections and strategies for managing resistance, such as prudent antibiotic use, development of new drugs, and controlling spread. It concludes that human overuse of antibiotics has led to widespread resistance and that improved hygiene and isolation can help control spread.
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.
antibiotics are necessary to treat infections and chemotherapeutic agents are also used for this purpose. Chemotherapeutic agents are also used in the treatment of cancers. These therapeutic agents have limitations, specific action and a set mode of action. We can say that they are selective. The antibiotics are natural as well as synthetic in nature and have specificity for action against the microorganisms. Chemotherapeutic agents are chemical in nature and are synthesised in labs. They are less selective in action.
The document provides an overview of pharmacology of antimicrobials including:
1. It classifies antimicrobials by the microorganism they affect such as antibacterial, antifungal, and antiviral drugs.
2. It discusses important concepts such as bacteriocidal vs. bacteriostatic effects, selective toxicity, and organism sensitivity.
3. It covers antimicrobial resistance including common mechanisms and factors that promote development of resistance.
Antimicrobial agents work by interfering with essential processes in microorganisms like bacteria, fungi and parasites. They are commonly used to treat infections caused by these microorganisms. There are several classes of antimicrobial agents classified based on their chemical structure and mechanisms of action. Some common mechanisms include inhibiting cell wall synthesis, disrupting cell membranes, and inhibiting protein or nucleic acid synthesis. Microorganisms can develop resistance to antimicrobial agents through various mechanisms such as enzymatic modification, target site alterations, and efflux pumps. Antibiotic sensitivity testing helps determine the most effective antibiotic for treating a bacterial infection.
What are antibiotics? How do antibiotics work? Antibiotic Mode Of Action. DETERMINANTS OF RATIONAL DOSING. CHEMOTHERAPEUTIC SPECTRA , Principles of Antibiotic Therapy .Empirical Antibiotic Therapy , Factors Influencing Antibiotic Choice. Prophylaxis for Selected Types of Surgery
This document provides an overview of basic principles of antimicrobial therapy. It discusses key terms like antimicrobial, pharmacodynamics, pharmacokinetics and selective toxicity. It also covers topics like antibiotic resistance, restricted antibiotics, selection of antibiotics, antibiotic combinations, classification of antimicrobials by category and common drugs and their indications and adverse drug reactions. The document serves as a comprehensive reference on fundamental concepts in antimicrobial treatment and management.
This document discusses antibiotics, including their classification, mechanisms of action, uses, and side effects. It covers several classes of antibiotics such as penicillins, cephalosporins, and their generations. Antibiotics work by inhibiting bacterial cell wall synthesis, disrupting cellular membranes, or interfering with protein, nucleic acid, or folic acid synthesis. Their use requires consideration of the infecting organism, patient factors, and development of resistance. Combination antibiotic therapy can have additive, synergistic, or antagonistic effects.
Rational Use of Antibiotics. Infection was a major cause of morbidity and mortality, before the development of antibiotics.
The treatment of infections faced a great challenge during those periods.
Later in 1928, the discovery of Penicillin, a beta-lactam antibiotic, by Alexander Fleming opened up the golden era of antibiotics.
It marked a revolution in the treatment of infectious diseases and stimulated new efforts to synthesize newer antibiotics.
The period between the 1950s and 1970s is considered the golden era of discovery of novel antibiotic classes, with very few classes discovered since then.
Antibiotic resistance occurs when bacteria change in response to antibiotic use, making infections harder to treat. Bacteria, not humans or animals, become resistant. This leads to higher medical costs, prolonged hospital stays, and increased deaths. Antibiotic resistance threatens global health and can affect anyone, of any age, in any country. It occurs naturally but also because of misuse of antibiotics in humans and farm animals. This is making many infections like pneumonia, tuberculosis, and gonorrhea more difficult to treat.
Principles of antimicrobial therapy - PharmacologyAreej Abu Hanieh
This document discusses antimicrobial therapy and antibiotic selection and use. It provides information on:
- How antimicrobials target biochemical differences between microbes and humans
- Factors to consider when selecting an antibiotic, including the microbe, site of infection, and patient factors
- How bacteriostatic and bactericidal drugs work differently
- Key concepts regarding pharmacodynamics and pharmacokinetics of antimicrobial drugs
- Common classes of antibiotics like penicillins, cephalosporins, aminoglycosides and their mechanisms of action
The document discusses promoting fetal and maternal health through the nursing process of assessment, diagnosis, planning, and evaluation. It covers topics like health promotion during pregnancy, common discomforts at different stages, preventing exposure to teratogens, and addressing maternal stress. The overall goal is to describe strategies nurses can use to promote healthy behaviors and outcomes for both mother and baby.
This document discusses obstructive pulmonary disorders, specifically asthma, acute bronchitis, and chronic bronchitis. It provides details on the etiology, pathogenesis, clinical manifestations, diagnosis, and treatment of each condition. Asthma is characterized by airway inflammation and reversible airway obstruction. Acute bronchitis involves acute inflammation of the bronchi typically caused by viral or bacterial infections. Chronic bronchitis involves recurrent cough and mucus production for at least three months in two consecutive years, usually caused by long-term smoking.
PFA Training - Feb 2022 - part 1dddddddddddddddd.pptxmousaderhem1
This document provides training on supporting preparation for adulthood for young people with special educational needs. It discusses the importance of focusing on employment, independent living, community participation, and health from age 14. Schools are legally required to support preparation for adulthood as part of annual reviews for students with education, health, and care plans. The training emphasizes taking a person-centered approach and focusing on students' aspirations as they plan for transition to adult life. An overview of best practices and timelines is provided to guide education providers in effectively supporting students in preparing for adulthood.
Competency Based Education - Part FFFFFFFFFFFFFFFFFFFFFFFFI.pptxmousaderhem1
This document provides an overview of competency-based education (CBE) and the California Community Colleges' (CCCs) plans to implement CBE. It discusses:
1. The background and goals of CBE, including helping students achieve credentials faster and meeting the CCCs' Vision for Success.
2. Definitions of CBE from various sources and how it differs from traditional credit-based models by focusing on mastery of competencies over time spent.
3. The CCCs' plans to implement direct assessment CBE programs, including drafting new regulations, establishing a CBE pilot collaborative, and providing support for campuses.
4. An invitation to the next session which
This document provides an overview of competency-based education (CBE) programs in higher education. It defines CBE and discusses why institutions are adopting this model. It describes the characteristics of CBE programs, including being learner-centered, focusing on learning over time, allowing flexible pacing, and using authentic assessments. The document outlines some examples of CBE programs at institutions like Lipscomb University, Texas A&M University-Commerce, Brandman University, and the University of Michigan. It also discusses the roles of faculty in CBE programs and regulatory guidelines around CBE from the federal level.
Digestive System ooooooooooooooooooooooooooooooooooooooooooooooooooopptmousaderhem1
The document summarizes the key components and functions of the human digestive system. It describes the main phases and types of digestion, as well as the organization of the gastrointestinal tract. It provides details on the roles and processes of the mouth, esophagus, stomach, small intestine, large intestine, and accessory organs like the liver, gallbladder and pancreas in breaking down food and absorbing nutrients into the bloodstream.
GIT DRUG FFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFFmousaderhem1
The gastrointestinal tract extracts nutrients from food and converts it into an absorbable form. It is made up of several organs like the mouth, esophagus, stomach, small intestine, and large intestine. The gastrointestinal tract walls contain four layers - mucosa, submucosa, muscularis externa, and serosa - to aid in digestion and absorption of nutrients. Saliva aids in digestion and protects the oral cavity. It is produced by three pairs of salivary glands - parotid, submandibular, and sublingual glands - and contains water, enzymes, and antibodies.
Colorectal cancer (CRC) incidence varies globally, with higher rates in industrialized areas. CRC risk factors include genetic predisposition, inflammatory bowel disease, height, obesity, diet, lifestyle factors, and medication use. Diets high in vegetables and physical activity likely decrease CRC risk, while alcohol, red meat and processed meat probably or possibly increase risk. Factors such as fiber, folate, aspirin, and NSAIDs may also influence CRC risk, but evidence is currently insufficient. Overall, lifestyle and dietary modifications could help lower CRC incidence.
This document discusses neuromodulation techniques for the treatment of chronic pain, specifically noninvasive brain stimulation methods like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). It provides background on the pathophysiology of chronic pain and how plastic changes in the nervous system can lead to maladaptive changes. Several clinical studies applying TMS and tDCS over the motor cortex for different chronic pain conditions like spinal cord injury, fibromyalgia and visceral pain are summarized. The document acknowledges the promising initial results but also limitations and need for more research to optimize stimulation parameters and fully understand individual variability in responses.
This document discusses prostate cancer, including its definition, causes, risk factors, clinical manifestations, management, and nursing care. Prostate cancer is a malignant tumor that usually grows slowly and remains confined to the prostate gland for many years but can advance and spread to other tissues. Management may include radical prostatectomy surgery, hormonal therapy, radiation therapy, cryotherapy, or chemotherapy. Post-operative nursing care focuses on monitoring for complications, caring for urinary catheters, encouraging mobility, and providing routine post-operative support.
This study investigated the effects of conventional breathing exercises (BTE) and inspiratory muscle training (IMT) over 12 weeks on 60 adult asthma patients aged 40-65. Patients were randomly assigned to either BTE or IMT groups. Outcome measurements before and after the intervention found that while both groups improved asthma control test scores, only the IMT group saw a significant increase in forced vital capacity. The study concluded that a representative IMT protocol of 30 breaths twice daily at 50% of maximal inspiratory pressure can increase inspiratory muscle strength and improve functional capacity and physical activity in middle-aged and older adults with moderate to severe asthma.
The Clinical Nurse Leader (CNL) is a master's-prepared nurse who oversees care coordination and provides direct patient care. The CNL focuses on leadership, patient outcomes, the care environment, and management. CNL certification is granted by the Commission on Nurse Certification and requires an RN license, a master's degree from an accredited CNL program, and passing a certification exam.
The document discusses various vascular diseases including their symptoms, causes, risk factors, diagnostic tests, and treatment options. It covers conditions such as peripheral artery disease, deep vein thrombosis, varicose veins, Raynaud's phenomenon, and Buerger's disease. Diagnostic tests mentioned include Doppler ultrasound, ankle-brachial index testing, angiography, MRI, and CT angiography. Treatment may involve medications to improve blood flow, reduce clotting, or lower cholesterol. Surgery is also an option for some conditions.
Discuss methods of investigation in case of oroantal fistula.pptxmousaderhem1
This document discusses methods of investigating oroantral fistulas. It begins with defining an oroantral fistula as an abnormal connection between the oral cavity and maxillary sinus. It then outlines various investigation methods including patient history, physical examinations like the nose blowing test, mouth mirror test, and suction test. It also mentions using radiological exams like x-rays of the paranasal sinuses and orthopantomograms. The goal is to understand a patient's symptoms and clinically examine them to diagnose an oroantral fistula.
English Drug and Alcohol Commissioners June 2024.pptxMatSouthwell1
Presentation made by Mat Southwell to the Harm Reduction Working Group of the English Drug and Alcohol Commissioners. Discuss stimulants, OAMT, NSP coverage and community-led approach to DCRs. Focussing on active drug user perspectives and interests
Mental Health and well-being Presentation. Exploring innovative approaches and strategies for enhancing mental well-being. Discover cutting-edge research, effective strategies, and practical methods for fostering mental well-being.
As Mumbai's premier kidney transplant and donation center, L H Hiranandani Hospital Powai is not just a medical facility; it's a beacon of hope where cutting-edge science meets compassionate care, transforming lives and redefining the standards of kidney health in India.
At Apollo Hospital, Lucknow, U.P., we provide specialized care for children experiencing dehydration and other symptoms. We also offer NICU & PICU Ambulance Facility Services. Consult our expert today for the best pediatric emergency care.
For More Details:
Map: https://cutt.ly/BwCeflYo
Name: Apollo Hospital
Address: Singar Nagar, LDA Colony, Lucknow, Uttar Pradesh 226012
Phone: 08429021957
Opening Hours: 24X7
We are one of the top Massage Spa Ajman Our highly skilled, experienced, and certified massage therapists from different corners of the world are committed to serving you with a soothing and relaxing experience. Luxuriate yourself at our spas in Sharjah and Ajman, which are indeed enriched with an ambiance of relaxation and tranquility. We could confidently claim that we are one of the most affordable Spa Ajman and Sharjah as well, where you can book the massage session of your choice for just 99 AED at any time as we are open 24 hours a day, 7 days a week.
Visit : https://massagespaajman.com/
Call : 052 987 1315
COLOUR CODING IN THE PERIOPERATIVE NURSING PRACTICE.SamboGlo
COLOUR CODING IN THE PERIOPERATIVE ENVIRONMENT HAS COME TO STAY ,SOME SENCE OF HUMOUR WILL BE APPRECIATED AT THE RIGHT TIME BY THE PATIENT AND OTHER SURGICAL TEAM MEMBERS.
Chandrima Spa Ajman is one of the leading Massage Center in Ajman, which is open 24 hours exclusively for men. Being one of the most affordable Spa in Ajman, we offer Body to Body massage, Kerala Massage, Malayali Massage, Indian Massage, Pakistani Massage Russian massage, Thai massage, Swedish massage, Hot Stone Massage, Deep Tissue Massage, and many more. Indulge in the ultimate massage experience and book your appointment today. We are confident that you will leave our Massage spa feeling refreshed, rejuvenated, and ready to take on the world.
Visit : https://massagespaajman.com/
Call : 052 987 1315
The Importance of Black Women Understanding the Chemicals in Their Personal C...bkling
Certain chemicals, such as phthalates and parabens, can disrupt the body's hormones and have significant effects on health. According to data, hormone-related health issues such as uterine fibroids, infertility, early puberty and more aggressive forms of breast and endometrial cancers disproportionately affect Black women. Our guest speaker, Jasmine A. McDonald, PhD, an Assistant Professor in the Department of Epidemiology at Columbia University in New York City, discusses the scientific reasons why Black women should pay attention to specific chemicals in their personal care products, like hair care, and ways to minimize their exposure.
The facial nerve, also known as cranial nerve VII, is one of the 12 cranial nerves originating from the brain. It's a mixed nerve, meaning it contains both sensory and motor fibres, and it plays a crucial role in controlling various facial muscles, as well as conveying sensory information from the taste buds on the anterior two-thirds of the tongue.
About this webinar: This talk will introduce what cancer rehabilitation is, where it fits into the cancer trajectory, and who can benefit from it. In addition, the current landscape of cancer rehabilitation in Canada will be discussed and the need for advocacy to increase access to this essential component of cancer care.
2. Definition
Chemotherapy is the science that deals with the
treatment of disease by means of chemicals
(chemotherapeutic agents) that have a specific
toxic effect upon the disease-producing
microorganisms or that selectively destroy
cancerous tissue.
Chemotherapeutic agents are:
• Antibacterial drugs including antibiotics
• Antifungal drugs
• Antiviral drugs
• Antiprotozoal drugs
• Anticancer drugs.
3. Antibiotics (major chemotherapeutic
agents) are defined as:
Any chemical substances produced by
various microorganisms and fungi,
having the capacity (in dilute solutions)
to inhibit the growth of or to destroy
other microorganisms; used chiefly in
the treatment of infectious diseases.
Some of antibiotics could be used in
treatment of cancer diseases.
4. Characteristics of clinically useful
Antibiotics
•It should have a wide spectrum of activity
with the ability to destroy or inhibit
different species of pathogenic organisms.
• It should be nontoxic to the host and
without undesirable side effects.
• It should be non-allergenic to the host.
• It should not eliminate the normal flora of
the host.
5. Characteristics of clinically useful
Antibiotics
• It should be able to reach the part of the
human body where the infection is
occurring.
• It should be inexpensive .
• It should be chemically-stable(have a long
shelf-life).
• Microbial resistance is uncommon and
unlikely to develop.
6. Patient–Drug–Pathogen interaction.
In the laboratory the strain of pathogen, the
number of infecting organisms, the culture
medium, the antibiotic concentration, and
the duration of antibiotic exposure can be
precisely specified.
This precision cannot be obtained in patients
since chemotherapy of human disease is
complex, as it depends on a complex patient–
drug–pathogen interaction.
7. This interaction has six components:
Pharmacokinetics (What the patient does to
the drug)
Pharmacodynamics (What the drug does to
the patient)
Immunity (What the patient does to
pathogen)
Sepsis-Infection (What the pathogen does to
patient)
Resistance (What the pathogen does to the
drug)
Selective toxicity (What the drug does to the
pathogen).
8. Pharmacokinetics
To be clinically useful, a chemotherapeutic
drug must have both:
Selective toxicity against pathogen.
Favorable pharmacokinetics.
The concentration of the drug in a
patient’s body as a function of time is
determined by the dose administered &
the drug’s pharmacokinetics.
9. Absorption
Oral Absorption can be affected by drugs and by
food.
Aluminum, calcium, and magnesium ions in
antacids or dairy products form insoluble chelates
with all Tetracyclines and inhibit their absorption.
Systemic use of drugs that are poorly absorbed or
are destroyed by GI environment requires
parenteral administration. If the goal is to attack
pathogens in GIT then poor GIT absorption may
be an advantage.
10. Pharmacokinetics
An antibiotic that is itself nontoxic may have
metabolites that are toxic, diminishing its
usefulness.
For example, Imipenem is hydrolyzed by renal
dipeptidase to a metabolite that is inactive against
bacteria but is toxic to humans.
Co- administration of cilastatin inhibits the renal
dipeptidase, which both prevents the formation of
the toxic metabolite and decreases Imipenem
clearance, prolonging the half-life of the drug.
11. Partitioning
Partitioning of some drugs into cells
occurs.
Macrolides and Flouroquinolones are
selectively partitioned into cells which
accounts in part for their efficacy
against mycoplasma and Chlamydia
(intracellular pathogens).
12. The concentrations of chemotherapeutic
drugs in plasma, CSF, urine, or ascites
fluid can be measured to determine
whether sufficient drug is present to
inhibit or kill a given pathogen and to
ensure that the concentration is not so
high as to be toxic to the patient.
(e.g. Aminoglycosides)…..TDM
13. Pharmacodynamics
In the case of antibiotic chemotherapy, the
ideal Pharmacodynamics response is usually
obtained; the pharmacological target is not
normal human cells but rather a pathogen,
parasite, a virus-infected human cell, or a
cancerous cell. The less selective the
chemotherapeutic drug, the greater the
severity of adverse effects.
14. Pharmacodynamics
Comparing with other drugs, antibacterial
chemotherapeutic drugs are remarkably safe.
Toxicity is common mainly in patients who are
given inappropriately high doses or who
develop high drug levels because of decreased
drug clearance.
Most antibiotics are renally cleared, so renal
failure is a common cause of diminished
antibiotic drug clearance
16. Adverse effects associated with the
use of Antibacterials
Allergic reactions.
Toxic reactions resulting from inappropriate high
doses.
Interactions with other drugs.
Reactions related to alterations in normal body
flora “Superinfection”(e.g. Clindamycin-induced
pseudomembranous colitis).
Idiosyncratic reactions( due to pharmacogenetics
e.g. sulfonamide causing severe RBC hemolysis in
people having G6PDH deficiency).
17. Allergic Responses
Immediate hypersensitivity reactions
(anaphylaxis).
Delayed sensitivity reactions (interstitial
nephritis).
Hapten-mediated serum sickness. Allergic
cross-reactions to structurally related
antibiotics can occur.
18. Superinfection
Many antibiotics alter the enteric microbial
flora, particularly if high concentrations reach
the colon. Antibiotic-sensitive bacteria are
suppressed or killed, thereby removing their
inhibitory effects on potentially pathogenic
organisms. Overgrowth of pathogenic microbes
can then occur.
For example, Clostridium difficile is resistant to
Clindamycin. Use of such an antibiotic permits
the proliferation of C. difficile, which then
elaborates its toxin in high concentration.
This toxin can cause PMC, which can be fatal if
not recognized and treated.
19. Immunity
The effectiveness of chemotherapeutic
agents is enhanced by adequate
immune function; however, some
antibiotics suppress immune function.
20. Immunity
In the absence of antibiotic therapy, many
patients survive infection, even infection by
highly virulent pathogens. Thus, immunity
may be due to factors such as a high
functional reserve of organs or to an
enhanced nonspecific Opsonization (the
process by which a pathogen is marked for
ingestion and destruction by a phagocyte) of
pathogens by complement.
21. Immunity
In other cases, specific partial immunoglobulin
IgG–mediated immunity was produced during
prior exposure to the pathogen or a new IgM-
mediated immunity develops during the course
of the infection. Specific immunity can be
either cell mediated or antibody mediated &
may be enhanced by endogenous cytokines.
Exogenously administered cytokines also may
prove clinically useful as adjuncts to antibiotic
chemotherapy.
22. Sepsis
It is a reaction to severe infections in which a
variety of mediators are released. Some of these
mediators are bacterial metabolic products, while
others are cytokines produced by humans during
infection.
These mediators can induce failure of several organ
systems. Cardiac function can be suppressed; acute
respiratory distress syndrome can occur; and renal
failure is common.
Through their ability to cause cell lysis, antibiotics
(Beta-lactams or Aminoglycosides )may increase the
release of bacterial mediators (e.g. endotoxin).
23. Sepsis
Antibiotics also may induce the release
of endogenous cytokines, such as
interleukin (IL- 1 , IL-6, and TNF from
monocytes and IL-4 and IFN- from
lymphocytes.
These cytokines are important in
immunological responses and may
contribute to the development of sepsis.
24. Bacterial Resistance
• A resistance to an antibiotic can be the result of
one or more mechanisms. Alterations in the
lipopolysaccharide structure of gram-negative
bacilli can affect the uptake of lipophilic drugs.
Similarly, changes in porins can affect the uptake of
hydrophilic drugs. Once the drug enters the cell, it
may be enzymatically inactivated. Some bacteria
possess pumps that remove drugs from the
bacterial cytosol. The antibiotic also may be
ineffective as a result of mutation of genes coding
for the target site (e.g., penicillin-binding proteins,
DNA gyrase, or ribosomal proteins).
26. Bacterial resistance
Acquired resistance, is a result of the following:
Spontaneous, random chromosomal
mutations:
These mutations are commonly due to a
change in either a structural protein receptor
for an antibiotic or a protein involved in drug
transport.
27. Bacterial Resistance
Extrachromosomal transfer of drug-resistant genes
Transformation is transfer of naked DNA between cells of
the same species.
Transduction via R plasmids is asexual transfer of plasmid
DNA in a bacterial virus between bacteria of the same
species.
Conjugation is the passage of genes from bacteria to
bacteria via direct contact through a sex pilus or bridge.
Conjugation occurs primarily in gram-negative bacilli, and it
is the principal mechanism of acquired resistance among
enterobacteria.
Transpositions occur as a result of movement or “jumping”
of transposons (stretches of DNA containing insertion
sequences at each end) from plasmid to plasmid or from
plasmid to chromosome and back.
28. Selective targeting
(Selective toxicity)
• The goal of chemotherapeutic agents is
selective toxicity, i.e. inhibiting pathways
or targets that are critical for pathogen
or cancer cell survival and replication at
concentrations of drug lower than those
required to affect host pathways.
29. Selectivity can be realized by
1. Targets (metabolic pathways, enzymes, genes)
unique to the pathogen or cancer cell that are not
present in the host.
One attractive target for antibacterial drugs is
the bacterial Peptidoglycan cell wall. This structure
is both biochemically unique and essential for the
survival of growing bacteria.
(Beta-lactams antibiotics inhibit transpeptidase
enzymes that catalyze the final cross-linking step
in Peptidoglycan synthesis).
30. Selectivity
Fungi present two unique targets (cell wall
and ergosterol) that are exploited by
antifungal drugs:
Echinocandins inhibit beta-(1, 3)-D-Glucan,
essential component of fungal cell wall.
Azoles inhibit ergosterol biosynthesis in
fungal cells changing their permeability
and cause cell death
31. Selectivity
2. Targets in the pathogen or cancer cell that
are similar but not identical to those in the
host. Many organisms have metabolic
pathways similar to those of human but,
because of evolutionary divergence, possess
distinct enzyme or receptor isoform.
Drugs can have quantitatively different
binding specificities based on these
biochemical differences.
32. Selectivity
Example: Inhibitors of dihydrofolate reductase( DHFR)
DHFR is a crucial enzyme in the synthesis of purines &
pyramidines building blocks of DNA. Human, bacteria,
and protozoa all utilize DHFR in DNA synthesis, but the
DHFR isoforms are genetically and structurally distinct
and can therefore be targeted by different drugs.
Methotrexate powerfully inhibits DHFR in human as
well as bacterial and protozoal cells & this drug’s low
selectivity produce high toxicity in man. In contrast,
Trimethoprim selectively inhibit bacterial DHFR and
Pyrimethamine selectively inhibits the malarial DHFR.
33. Lethal vs Inhibitory effects
of Antibiotics
Antibiotics can be classified according to their effects
on the molecular biology of bacteria.
Ribosomal inhibitors (Macrolides).
Cell wall disrupters (beta -lactams).
DNA disturbers (Flouroquinolones).
Metabolic poisons (trimethoprim-sulfamethoxazole)
35. Bactericidal Effects
(Irreversible)
These effects are the result of the disruption
of the cell wall or membrane. Cell lysis may
occur when water diffuses into the high-
osmolarity bacterial cytosol through the
antibiotic-induced holes in the membrane,
causing the bacteria to swell and burst.
Cidal effects also can occur as a consequence
of inhibition of bacterial DNA replication or
transcription.
36. A cidal drug may prove to be merely static if
an inappropriately low dose or short
treatment course is prescribed.
A static drug may be cidal if given in high
doses for prolonged courses to exquisitely
sensitive pathogens.
37. Static Effects
(Reversible)
For example, inhibition of folate synthesis
interferes with methylation, a biochemical
synthetic process. Reversal of this static effect
can occur when the antibiotic concentration falls
or if a compensatory increase in the synthesis of
the inhibited enzymes occurs. The place of a
drug along this spectrum will depend on both
the pharmacological properties of the drug and
such clinical factors as immune system function,
drug concentration in tissue, and duration of
therapy.
38. Bactericidal Antibiotics Bacteriostatic
Antibiotics
Concentration -dependent Time- dependent
Aminoglycosides Beta-Lactams
Bacitracin Isoniazid
Quinolones Metronidazole
Rifampicin
Vancomycin
Pyrazinamide
Tigecycline
Tetracyclines
Chloramphenicol
Clindamycin
Macrolides
Oxazolidinones
Sulfonamides
Trimethoprim
1. Drug may be static against one organism and cidal against another.
2. Concentration-dependent cidal agents have a rate of killing that increases with
drug concentration, while time-dependent cidal agents exhibit constant rate of
killing independent of drug concentration.
39. Selection of Antibiotics
Factors taken into consideration:
The identity of the infecting organism.
Drug sensitivity of the infecting organism
Host factors (site of the infection, status of
host defenses).
Empiric therapy prior to completion of lab.
tests: it may be necessary to begin treatment
in patients with serious infections before the
lab results.
40. Host Factors
Host defenses (immune system and phagocytic
cells).
Site of infection: to be effective an antibiotic
must be present in the site of infection in a level
greater than MIC endocarditis, meningitis.
Age (infants and elderly highly vulnerable to drug
toxicity).
Pregnancy and lactation.
Previous allergic reactions.
Genetic factors (hemolysis in patients with G-6PD
deficiency if given sulfonamides).
41. Combination Chemotherapy
Combination chemotherapy is recommended
for chronic infections (tuberculosis, AIDS ) and
most anticancer drug regimens.
There are several reasons to administer
multiple drugs simultaneously in a combination
chemotherapy regimen:
The use of multiple drugs with different
mechanisms of action targets multiple steps in
microbial or cancer cell growth leading to the
maximal possible rate of cell killing.
42. Combination Chemotherapy
The use of combinations of drugs that target
different pathways or molecules in pathogen or
cancer cell makes it more difficult for resistance to
develop.
The use of lower doses of synergistically acting
drugs in the combination can reduce drug-induce
adverse effects. This is especially important in
antimicrobial chemotherapy, where synergistic
activity ofdrug combinations has been clearly
demonstrated.
43. Combination Chemotherapy
Because many anticancer drugs have different
dose-limiting adverse effects, it is often possible to
give each drug to its maximally tolerated dose and
thereby achieve increased overall cell killing.
The concept of combination chemotherapy is
being redefined as new treatments become
available.
In the future, immunotherapies, hormone
therapies, and biotherapies will become
increasingly integrated into combination
chemotherapy regimens (Protein therapeutics).
44. Combination Chemotherapy
The combination of two bactericidal drugs
can be synergistic (greater than the sum of
the effects of each drug alone).
The combination of two Bacteristatic drugs
can also be synergistic, but in most cases it
can result in additive effects
45. Disadvantages of combination
chemotherapy (Unfavorable)
Bacteristatic and bactericidal effects are also
important to consider when antibiotics are
used clinically in combination. The combination
of Bacteriostatic drug with bactericidal drug
can result in Antagonistic effects.
46. Disadvantages of combination
For example: The Bacteristatic drug
(Tetracycline) inhibits protein synthesis and
thereby retards cell growth and division.
The action of this drug antagonizes the effect of
cell wall synthesis inhibitor (penicillin), which
requires bacterial growth in order to be
effective.
Clinical example: pneumococcal meningitis
treated by penicillin and tetracycline ?
47. Prophylactic Chemotherapeutic
(Chemoprophylaxis)
Antimicrobial and anticancer drugs are used
to treat overt diseases. These drugs can also
be used to prevent diseases from occurring
(prophylaxis), both before a potential
exposure and after a known exposure.
The potential benefit of chemoprophylaxis
must always be weighed against the risk of
creating drug-resistant pathogens or cancer
cells and the potential for toxicity due to
chemoprophylactic agent.
48. Prophylaxis
Antimicrobial prophylaxis is frequently used
in high-risk patients to prevent infection.
Travelers to malaria-infested areas often take
prophylactic antimalarial agent (Mefloquine).
Chemoprophylaxis can also be used in healthy
persons after exposures to certain pathogens.
Prophylactic therapy after known or suspected
exposure to gonorrhea, syphilis, meningitis, HIV,
and others can often prevent diseases
49. Non-surgical prophylaxis
Infection Indication Proper drug
Cholera Close contact Tetracyclines
Plague Close contact Tetracyclines
Anthrax Suspected exposure Ciprofloxacin or
Doxycycline
Tuberculosis Close contact INH, Rifampin, PZA
H.influenza infection Close contact Rifampicin
Meningococcal infection Close contact Rifampicin
Genital herpes simplex Recurrent infection Acyclovir
Otitis media Recurrent infection Amoxicillin
UTI Recurrent infection Co-trimoxazole
Malaria Travelers to endemic
area
Mefloquine
Rheumatic fever Rheumatic heart disease Benzathine penicillin
50. Surgical Prophylaxis
Chemoprophylaxis is also used in some
types of surgery to prevent wound
infections. Antibiotics are usually
administered prophylactically during
surgical procedures that could release
bacteria into the wound site.
51. Surgical Prophylaxis
Type of operation Pathogen Proper drug
Neurosurgical Staphylococci Cefazolin
Head and neck S.aureus Cefazolin
Gastroduodenal S.aureus Cefazolin
Biliary tract Enterococci Cefazolin
Cesarean section Anaerobes Cefazolin
Colorectal Anaerobes Cefoxitin, Cefotetan
Appendectomy Anaerobes Cefoxitin or Cefazolin +
Metronidazole
52. Pharmacology of Pathogens
Infections/ Classification:
Inhibitors of Folate metabolism:
Sulfonamides inhibit dihydropteroate synthetase.
Trimethoprim and Pyrimethamine, inhibit
dihydrofolate reductase.
Pharmacology of bacterial infections:
Inhibitors of DNA Replication (Topoisomerase II” DNA
gyrase” found mainly in Gram-negative bacteria:
(Quinolones) .
Inhibitors of Transcription (DNA-dependent RNA
polymerase): (Rifampicin).
Used mainly in tuberculosis & other infections.
53. Pharmacology of Pathogens
Infections/ Classification
Inhibitors of Translation (bind to bacterial ribosome and
Inhibit protein biosynthesis):
Drugs bind to 30 S ribosomal subunit :
Aminoglycosides, spectinomycin, and Tetracyclines
Drugs bind to 50 S ribosomal subunit:
Macrolides, Chloramphenicol, Lincosamines, streptogramins
and oxazolidines.
They are effective against both Gram-positive and Gram-
negative bacteria with a wide clinical uses.
Complete inhibition of protein synthesis is not sufficient to
kill the bacteria. Therefore, all of them are bacteriostatic,
except the Aminoglycosides.
They are not selective drugs since they affect mammalian
mitochondrial ribosome.
54. Pharmacology of Pathogens
Infections/ Classification
Inhibitors of bacterial and mycobacterial cell
wall synthesis:
Inhibitors of Murein monomer synthesis:
Cycloserine, Bacitracin and Fosfomycin.
Inhibitors of Murein polymerization:
Vancomycin, and Teicloplanin
Inhibitors of polymer cross-linking:
Beta-lactams.
Antimycobacterial agents:
Isoniazid, Ethambutol and Pyrazinamide.
57. Synthesis and Functions of Folic acid
Folate synthesis begins with the formation of
dihydropteroic acid from pteridine and PABA; this
reaction is catalyzed by dihydropteroate
synthetase. Glutamate and dihydropteroic acid
condense to form Dihydrofolic acid (DHF).
DHF is reduced to THF by dihydrofolate reductase.
THF serve as one-carbon donors in numerous
reactions necessary for the formation of DNA,
RNA, and proteins.
Note that bacteria synthesize folate de novo from
pteridine & PABA, whereas humans require dietary
folate.
59. Sulfonamides
They were the first modern agents to be used in
treatment of infections.
They are highly selective drugs, because
bacterial growth requires activity of the enzyme
that is inhibited by the sulfonamides, whereas
mammalian cells do not express this enzyme;
therefore, the use of these drugs is relatively
free of adverse effects (except in neonates).
60. Sulfonamides
Despite the selectivity of sulfonamides, the
development of resistance to these drugs has resulted in
their diminished use. Resistance can develop because of
overproduction of the endogenous substrate, PABA, for
the enzyme synthetase.
Sulfonamides are usually bacteriostatic drugs with
broad spectrum.
Because of the high incidence of resistance in the
bacterial population, these drugs are rarely used as
single drug. Instead, they are commonly used in
combination with synergistic drug such as Trimethoprim
and Pyrimethamine.
61. Pharmacokinetics
Absorption: varies from well absorbed
(sulfamethoxazole and sulfadiazine) to poorly
absorbed (Sulfasalazine).
Distribution: they distribute throughout body
fluids including cerebrospinal fluid (CSF). The
absorbed drugs can displace bilirubin from
binding sites on serum albumin leading to
kernicterus (Jaundice) in newborns. Elevated
concentration of free bilirubin in the blood
can lead to brain damage.
62. Pharmacokinetics
Metabolism: They are mainly acetylated,
and the acetylated metabolite has low
solubility in urine leading to crystallization.
Excretion: The largest fraction of the
acetylated metabolite is excreted in the
urine. The acidic urine can reduce its
solubility and may precipitate causing
crystaluria.
63. Adverse Effects of Sulfonamides
Crystaluria: characterized by hematuria and
proteinuria; it is treated by large volume of fluids
and alkalinization of urine. Newer Sulfonamides
(long acting drugs) such as Sulfisoxazole and
sulfadoxine are more soluble in urine.
Haemolytic anaemia (in persons with G-6-PDH deficiency).
Skin sensitization (Stevene-Johnson syndrome or
erythema multiform- life threatening
reaction).large doses may cause this serious
hypersensitivity. Skin condition in which cell death
causes the epidermis to separate from the dermis.
64. Therapeutic uses of Sulfonamides
Sulfonamides are preferred drugs for
treatment of acute uncomplicated urinary
tract infections (UTI) caused by susceptible
E. Coli.
Combination with Trimethoprim (Co-
trimoxazole) is always more effective in UTI.
Combination of Sulfadiazine and
Pyrimethamine is effective in treatment of
toxoplasmosis (parasitic infection).
65. Therapeutic Uses of Sulfonamides
Sulfasalazine is used in treatment of
ulcerative colitis. It is hydrolyzed by colonic
bacteria to sulfapyridine (antibacterial agent)
and 5-aminosalicylic acid (anti-inflammatory
agent).
Sulfamethoxazole is used in treatment of
pneumonia, enteritis and urithritis.
66. Sulfamethoxazole-Trimethoprim
Combination (Co-Trimoxazole)
A synergistic effect is obtained from this
combination since these two antibacterial
agents act on sequential steps in the pathway
of folic acid formation.
In order to obtain an optimal ratio of plasma
concentration (20/1), needed for the
synergistic effect, the two agents must be
administered in a ratio of (5 S/1 T).
67. Therapeutic Uses of Co-Trimoxazole
UTI: treatment of uncomplicated lower UI with
this combined product is highly effective.
Bacterial respiratory tract infections (chronic
bronchitis, otitis media and pneumonia caused
by pneumocystis carinii).
GIT infections (Typhoid fever & shigellosis).
68. Adverse Effects of Co-Trimoxazole
Similar to sulfonamides.
A possible teratogenic effect like all
antifolate drugs).
69. Sulfones (Dapsone)
They are used in treatment of leprosy and
pneumonia caused by pneumocystis carinii.
Synergistic effects can be obtained when they
combined with Trimethoprim.
They produce haemolytic anaemia and
methemoglobinemia in patients with
G-6-PDH deficiency.
70. Inhibitors of DNA Replication,
Transcription and Translation
• These processes are generally similar in bacteria and
humans. However, there are important differences in
biochemistry of bacterial and human central dogma
processes, and these differences can be exploited for
the development and clinical uses of antibiotics.
Three such differences are targeted by some
antibacterial drugs:
• Topoisomerases, which regulate supercoiling of DNA
and mediate segregation of replicated strands of DNA.
• RNA polymerases, which transcribe DNA into RNA.
• Ribosomes, which translate mRNA into protein.
71. Inhibitors of Topoisomerases:
Quinolones
• Fluoroquinolones are potentially
synthetic broad spectrum antibacterial
agents.
• They are related to Nalidixic acid, but
they have broader spectrum of activity
with less frequent development of
bacterial resistance.
72. Mechanism of Action of Quinolones
(Inhibition of DNA Gyrase)
The two strands of double helical DNA must be
separated to permit DNA replication or transcription.
However, anything that separates the strands results in
“overwinding” or excessive positive supercoiling of the
DNA in front of separation. To combat this mechanical
obstacle, the bacterial enzyme (DNA Gyrase) is
responsible for the continuous introduction of negative
supercoils into DNA. This is an ATP-dependent reaction
that requires that both strands of DNA be cut to permit
passage of a segment of DNA through the break; the
break is then resealed.
74. Mechanism of Action of Quinolones
(Inhibition of DNA Gyrase)
The DNA Gyrase of E.coli is composed of two
A-subunits and two B-subunits. The A-
subunits, which carry out the strand cutting
function of the gyrase , are the site of action
of (Quinolones).
These antibiotics inhibit Gyrase mediated
DNA supercoiling at a concentration that
correlate well with those required to inhibit
bacterial growth.
75. Mechanism of Action of Quinolones
(Inhibition of DNA Gyrase)
Mammalian cells do not contain DNA Gyrase.
However, they do contain a similar type of
DNA topoisomerase that removes positive
supercoils from eukorytic DNA to prevent its
tangling during replication. Quinolones
inhibit this type of enzyme only at much
higher concentrations.
76. Classification of Quinolones
Generation Agent Spectrum Site of infection
FIRST Nalidixic acid
Enoxacin
Norfloxacin
Gram Negative Urinary tract
SECOND Lomefloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
Gm (+) , (-)
Gm(-) P. aeruginos
Gm(+)/ chlamyd.
Urinary tract
Systemic
Systemic
THIRD Gatifloxacin
Levofloxacin
Moxifloxacin
Sparfloxacin
Gm (+) , (-)
Gm (+) , (-)
Gm (+) , (-)
Atypicals
Systemic,UT
Systemic,UT
Systemic,UT
Systemic,UT
FOURTH Trovafloxacin Gm (+) , (-)
Atypicals
Anaerobes
Systemic,
Urinary tract
77. Antibacterial Activities of Quinolones
They are highly active against wide range of
Gram negative( they have DNA gyrase) and
some of the agents have lower activity against
Gram-positive (They have Topoisomerase IV).
They do not have activity against anaerobes
(Except Sparfloxacin and Trovafloxacin).
They have activity against Ps.auroginosa
(Ciprofloxacin is more potent than Norfloxacin).
They have good tissue penetration, which is
advantage for deep-seated infections.
78. Pharmacokinetics of Quinolones
They are rapidly but variably absorbed with peak
concentration achieved in about 2 hours.
Food may decrease absorption, and Al- or Mg-
containing antacids inhibit absorption.
Bioavailability = 50-95% after oral dose.
Elimination half-life = 3-4 hours for ciprofloxacin, and
10-11 hrs for Pefloxacin and others.
Metabolism by liver & excretion by bile &/or urine.
Some of Quinolones are predominantly excreted by
kidneys (Ciprofloxacin, Ofloxacin), while others are
predominantly cleared by hepatic system (pefloxacin )
79. Therapeutic uses of Quinolones
UTI (caused by multiple resistant bacteria).
Prostatitis (Norfloxacin & ciprofloxacin are used.
Sexually transmitted diseases (STD): Quinolones
are active in N.gonorrheae, urethritis and
cervicitis. They are ineffective against
Treponema Pallidum(Syphilis).
Respiratory tract infections: They are effective
in bacterial bronchitis (Hemophilus ,& enteric
Gram-negative).They are more active than the
standard therapy against S.pneumoniae.
80. Therapeutic uses of Quinolones
Bacterial enteric infections:
Shigellosis, Salmonellosis, traveler’s diarrhea,
and biliary tract infections.
Bacterial endocarditis and meningitis:
Ciprofloxacin is more effective than synergistic
active combination of aminoglycosides and
Beta- Lactams in treatment of pseudomonal
endocarditis
Skin & soft tissues infections:
Ciprofloxacin is used.
81. Adverse Effects of Quinolones
GIT symptoms:
N.V., abdominal discomfort and anorexia.
CNS reactions: mild headache, dizziness, followed
by sleep disturbances or mood alteration.
Seizures are reported in small number of patients
(mechanism is associated with the ability of these
drugs to inhibit the specific binding of the inhibitory
neurotransmitters GABA” to synaptic membrane).
Hypersensitivity:
(skin rashes followed by pruritis).
Photosensitivity:
Only halogenated derivatives (Sparfloxacin and
lomefloxacin ) can produce this effect.
82. Adverse Effects of Quinolones
Arthropathy (Cartilage damage and tendon
rupture): Because of the potentiality for this
toxicity in growing children, these drugs should
not be used in Children.
Laboratory tests abnormalities: Abnormal
laboratory values associated with the
Quinolones include: eosinophilia, leukopenia,
neutropenia & elevation of liver enzymes.
83. Adverse Effects of Quinolones
Second generation Flouroquinolones
(ciprofloxacin) interact with Theophylline by
decreasing its clearance, which leads to
Theophylline toxicity.
Co-administration of thioridazine
(antipsychotic agent) with ciprofloxacin
increases the risk of Cardiotoxicity.
84. Inhibitors of Transcription:
Rifamycin derivatives
Rifampicin and Rifabutin are two
semisynthetic derivatives of naturally
occurring Rifamycin B.
Although Rifampicin can be used for
prophylaxis of meningitis and for treatment
of some other bacterial infections, its major
use is in treatment of TB and other
mycobacterial infections.
85. Antibacterial activity of Rifampicin
It is a large lipid-soluble molecule that
is bactericidal for microorganisms such
as staphylococcus aureus, Neisseria
meningitides, Haemophilus influenzae,
Mycobacterial tuberculosis, Chlamydiae
and certain viruses.
86. Mechanism of action of Rifampicin
Rifampicin binds strongly to β-subunit of
bacterial DNA-dependent RNA polymerase and
thereby inhibits RNA synthesis. Resistance
results from any one of several possible point
mutations in rpoβ, the gene for the β- subunit
of RNA polymerase.
Rifampicin displays high selectivity for bacteria,
as mammalian polymerases are inhibited by
Rifampicin only at far higher concentrations.
Hence, Rifampicin is generally well tolerated,
and the incidence of adverse effects is low.
87. Bacterial Transcription
Gene expression begins with transcription,
which involves the synthesis of single stranded
RNA transcripts from DNA template.
Transcription is catalyzed by the enzyme RNA
polymerase.
The process of transcription occurs in 3 stages:
Initiation, elongation and termination.
The RNA polymerase enzyme differs between
bacteria and humans and thus can serve as a
selective target for antibacterial action.
88. Pharmacokinetics of Rifampicin
Rifampicin is absorbed orally and widely
distributed into many tissues and fluids
including CSF.
It excreted mainly in bile (enterohepatic
cycling), but some of its metabolite
(deacetylated) appears in urine, sweat,
tears causing harmless orange -reddish
discoloration.
89. Clinical uses of Rifampicin
Indiscriminate use of Rifampicin for
minor infections may favor the
widespread selection of Rifampicin-
resistant mycobacterium and thus
deprive the drug of most of its
usefulness.
90. Clinical uses of Rifampicin
It is used to prevent meningococcal disease in
individuals who have had close contact with
N.meningitidis-infected patients.
It is used in combination with Vancomycin and
Gentamycin for the treatment of Staphylococcal
endocarditis or Osteomylitis.
It is used as alternative to INH for the prevention of
TB in HIV-positive persons (when there is a resistance
to INH).
It is usually combined with INH & Pyrazinamide for
the initial treatment of TB.
It can be used in treatment of tubercular
meningitis, since it can penetrate BBB.
91. Adverse effects of Rifampicin
Abdominal symptoms (epigastric distress, nausea and
vomiting).
Hepatotoxicity: Hepatitis from Rifampicin rarely
occurs in patients with normal liver function;
however, chronic liver disease, alcoholism , old age
and drugs(INH) appear to increase the incidence of
severe hepatic problems when Rifampicin is given.
Flu-like symptoms (fever, chills and myalgia) as an
immune-mediated effect with thrombocytopenia.
Teratogenicity (it is contraindicated during pregnancy)
92. Unwanted Effects
• Potent induction of CYP450 enzymes
that leads to the reduction of half-life of
many drugs such as digoxin, & oral
anticoagulants. It is more complicated in
TB therapy in HIV-infected patients
receiving protease inhibitors & reverse
transcriptase inhibitors.
93. Inhibitors of Bacterial Translation
(Ribosomes)
Bacterial protein synthesis:
Once the mRNA transcripts are synthesized,
these transcripts are translated by the
bacterial translational machinery. Although
the overall process of translation is similar
between bacteria and higher organisms,
there are a number of pharmacological
differences in the details of the mechanisms.
96. Protein Biosynthesis
1. Initiation :
• 1. Activation of amino acids (first a.a. is methionine).
• (A.A.)1 + ATP (A.A.)1 –AMP
• activating enzyme
2. Formation of Aminoacyl-tRNA complex.
• (A.A)1-AMP + tRNA (A.A)1-tRNA1
• (specific) Synthetase
3. Transcription of genetic information to mRNA.
30 S/50S initiation factor
• mRNA +(A.A)1-tRNA1 tRNA1-AA
97. 2. Elongations and Translocation:
tRNA2-AA2
tRNA1-AA1
peptide synthetase
tRNA2-AA2-AA1 Protein
3. Termination :
1.Formation of polyribosomes.
2.Assembly of amino acids into polypeptides.
3.Cleavage of the t-RNA-polypeptide-ribosome complex.
98. Protein Biosynthesis
The ribosome of E.coli has a sedimentation
coefficient of 70 S and is composed of a 30S subunit and
a 50S subunit.
The 70S subunit contains two sites that bind tRNAs
during translation: the P or “peptidyl” site, which
contains the growing peptide chain and the A or
“aminoacyl” site (acceptor site) which binds incoming
tRNA molecules carrying the various amino acids.
30S subunit is responsible for faithful decoding of the
mRNA message.
50S subunit catalyzes peptide bond formation
99. Protein Biosynthesis
Translation can be divided into 3 steps:
Initiation (the components of the translation
system assemble together).
Elongation (the addition of amino acids to the
carboxyl end of the growing polypeptide chain,
as the ribosome moves from the 5’-end to the
3’-end of the mRNA that is being translated.
Termination (proteins called release factors
recognize the termination codon in the A site
and activate discharge of the newly synthesized
protein and dissociation of the ribosome-mRNA
complex).
100. Considerations
Three considerations should apply to these drugs:
Translation inhibitors target either 30S or 50S
subunit of bacterial ribosome.
Complete inhibition of protein synthesis is not
sufficient to kill the bacteria. Bacteria can generate a
number of responses to various growth-stifling
treatments that allow them to remain dormant until
the treatment is removed. As a result, most protein
inhibitors are bacteriostatic, except aminoglycosides.
101. Selectivity: In addition to their inhibitory effect
s on bacterial ribosomes, these drugs can affect
mammalian mitochondrial and/or cytosolic
ribosomes. Inhibition of host ribosomes is one
common mechanism by which these drugs cause
adverse effects. For some antibiotics, such as
Chloramphenicol, inhibition of mammalian
ribosomes represents serious (lethal) toxicity.
Certain other antibiotics exhibit little or no
inhibition of mammalian ribosomes at clinically
relevant concentrations (dose limiting toxicity).
102. Pharmacology of Protein Inhibitors
Drugs targeting the 30S ribosome:
Aminoglycosides
Tetracyclines
Spectinomycin
Drugs targeting the 50S ribosome:
Macrolides
Chloramphenicol
Lincosamides
Streptogramins
Oxazolidinones.
105. Pharmacokinetics
They have a hexose nucleus, either streptodine or
deoxystreptamine to which amino sugars are attached
by glycosidic linkages. The amino groups are highly
basic and ionized, which can determine many of their
pharmacokinetic properties.
They are poorly absorbed from GIT and must
administered Pareneterally.
They are not metabolized, and their excretion by the
process of GF. They have limited tissue penetration
(accumulate in renal cortex and inner ear).
Monitoring of plasma levels is required step in therapy.
(2ug/ml for Gentamicin; 10 ug/ml for Amikacin are
associated with Nephrotoxicity).
106. Mechanism of Action
Aminoglycosides bind to 30S subunit and elicit
concentration-dependent effects on protein synthesis.
At low concentrations, they induce ribosomes to
misread mRNA during elongation, leading to synthesis
of proteins containing incorrect amino acids; i.e. amino-
glycosides interfere with mRNA decoding function of
the 30S subunit.
At higher concentrations, aminoglycosides
completely inhibit protein synthesis. They stimulate
tRNA movement in the opposite direction (reverse
translocation); where the ribosomes become
trapped at AUG start codons of mRNA.
Accumulation of these abnormal initiation
complexes stops the translation.
107. Pharmacological Aspects
In contrast to other protein inhibitors, AGs are
bactericidal.
The cell death induced by aminoglycosides is due to:
The aminoglycosides-induced misreading leads to
synthesis of aberrant proteins that insert into cell
membrane causing the formation of membrane pores,
which allow the drugs to flood the cell and stop
protein synthesis completely. As a result, the damage
to the membrane cannot be repaired, and leakage of
ions and larger molecules leads to cell death.
108. Aminoglycosides act synergistically
with Beta-lactam antibiotics; thereby
this combination is commonly used in
severe infections.
The inhibition of cell wall synthesis
(by beta-lactams) increases the entry
of aminoglycosides into the bacteria.
109. Single daily doses of Aminoglycosides are as effective
as and no more toxic than multiple daily doses. Single
daily dosing may be less nephrotoxic and ototoxic than
more frequent dosing. Since Aminoglycosides uptake
across proximal renal cortical tubular cells and inner ear
are saturable. The magnitude of rapid killing effect and
duration of the postantibiotic effects of aminoglycosides
are proportional to the peak concentration at the site of
infection; i.e. the higher the peak concentration, the more
pronounced these effects. Giving aminoglycosides as
single daily dose results in higher peak tissue
concentration than if the total daily doses were divided
and given more frequently.
110. Mechanism of Resistance
The clinically most common, is the plasmid-
encoded production of transferase enzyme or
enzymes that inactivate aminoglycosides by
adenylation, acetylation or phosphorylation.
Both amino and hydroxyl groups may be subject
to the enzymes attack (The metabolites formed
have reduced or no antibacterial activities).
Alteration in permeation or transport of AGs.
Receptor on 30 S ribosomal subunit may be
altered or deleted as a result of chromosomal
mutation.
111. Therapeutic Uses
Gentamicin, Amikacin and Tobramycin:
They are used in serious infections due to aerobic Gram-negative
bacilli including Pseudomonas aeruginosa.
They are used in treatment (with penicillins) of serious infections
(bacterial endocarditis).
Streptomycin: It is used in treatment of plague and multiple
drug-resistant TB.
Neomycin: It is used in empirical treatment of superficial
infections of skin.
Netlimicin: It is usually reserved for bacteria resistant to other
aminoglycosides.
112. Adverse Effects
Ototoxicity (manifesting as either auditory
or vestibular damage). The aminoglycosides
can accumulate in the perilymph and
endolymph of the inner ear, and at high
concentrations, to damage highly sensitive
hair cells. , these antibiotics may cause the
following disturbances when they are
administered for one month or longer:
(Impairment of hearing” deafness” and
disturbance of equilibration).
113. Nephrotoxicity can be manifested as a result of
drug accumulation in proximal tubular cells
Neuromuscular blockade; at very high
concentrations, aminoglycosides can produce
NM blockade, potentially causing respiratory
paralysis. This effect is thought to result from
drug competition with calcium at presynaptic
sites, leading to reduction in Ach release, failure
of the postsynaptic end-plate to depolarize, and
muscle paralysis.
115. Tetracyclines
Tetracyclines are broad-spectrum,
bacteristatic antibiotics that are used widely
in treatment of infections.
There are minor differences in clinical
efficacy of Tetracyclines that are related
largely to the pharmacokinetical properties.
116. Mechanism of Action
Tetracyclines bind reversibly to the 30S
subunit and inhibit protein synthesis by
blocking the binding of aminoacyl- tRNA to
the A site on the mRNA-ribosome complex.
This action prevents the addition of further
amino acids to the nascent peptide.
The high selectivity of Tetracyclines derives
from active accumulation of these drugs in
bacteria but not in mammalian cells.
117. Mechanism of Action
Tetracyclines enter Gram-negative bacteria
by passive diffusion through porin proteins in
the outer membrane, followed by active
transport across the inner cytoplasmic
membrane. Uptake into Gram-positive
bacteria occurs similarly via the energy-
dependent transport system. In contrast,
mammalian cells lack the active transport
system found in bacteria.
118. Mechanism of Resistance
Plasmid-encoded Efflux pumps represent
the most important mechanism in
Tetracyclines-resistant bacteria.
Production of proteins that interfere with
the binding of tetracycline to the ribosome.
Enzymatic inactivation of Tetracyclines.
119. Antibacterial Activity
The Tetracyclines possess a wide range of
antimicrobial activity against aerobic and
anaerobic Gram-positive and Gram-negative
bacteria. They also are effective against some
microorganisms such as Rickettsiae,
Mycoplasma, Chlamydia and Plasmodium.
Tetracyclines are bacteriostatic drugs.
120. Pharmacokinetics
Most of the Tetracyclines are incompletely and irregularly
absorbed from GIT.
The % of an oral dose is absorbed:
• Chlortetracycline (oral) 30%
• Demeclocycline (oral) 60-80%
• Doxycycline (oral & paraenteral) 95%
• Minocycline (oral) 100%
Absorption of Tetracyclines is impaired by the concurrent
ingestion of food(dairy products) or medications(antacids)
containing calcium & divalent or trivalent cations.
The mechanism responsible for the decreased absorption
appears to be chelation of these cations and Tetracyclines
(as chelating agents).
121. Pharmacokinetics
Tetracyclines distribute widely throughout
the body and into tissues and secretions
including prostate. They accumulate in the
liver, spleen, bone marrow and in bone and
enamel of the teeth.
Tetracycline cross the placenta and enter the
fetal circulation. Relatively high concentration
is found in breast milk.
122. Pharmacokinetics
Absorbed Tetracyclines are excreted mainly in
the bile and urine, with the urine (G.F.) being the
primary route for most tetracycline except
Doxycycline.
The renal clearance of Tetracyclines ranges
(10-90% ml/min):
Oxytetracycline 90 ml/min.
Chlortetracycline 30 ml/min.
Minocycline 9 ml/min. (Longer half life)
Doxycycline can be used in renally compromised
patients, because it is preferentially excreted via
the bile.
123. Therapeutic uses
Rickettsial infections (e.g. Rocky Mountain
spotted fever is characterized by fever, chills,
and aches in bones and joints).
Mycoplasma infections (pneumonia ,
common in people who live in close contact.
Chlamydial infections (non-gonococcal
urethritis, pelvic inflammatory disease,
pneumonia, hepatitis).
124. Therapeutic Uses
Bacillary infections ( Brucellosis and Cholera)
caused by brucella species and vibrio cholera.
( Doxycycline is preferred).
Spirochetal infections (Lyme disease)
transmitted by bite of infected ticks, results in skin
lesion, headache, &fever followed by meniningo-
encephalitis and arthritis.
(Single dose of Doxycycline can prevent the
development of the disease.)
UTIs (Tetracyclines are useless in UTIs caused by
Proteus and Pseudomonas).
125. Therapeutic Uses
Acne: benefits have been produced by small
doses by inhibiting proproni bacteria, which
reside in sebaceous follicles and metabolize
lipids to irritating FFAs, causing skin irritation &
gland Inflammation . (Minocycline is used).
Demeclocycline inhibits renal action of ADH
and is used in patients with ADH-secreting
tumors.
126. Adverse Effects
Gastrointestinal disturbances (epigastria
burning, abdominal discomfort, nausea
and vomiting).
Overgrowth of Candida in vagina or
Staphylococci in GIT may occur.
PMC caused by overgrowth of clost.
difficle (few cases).
127. Adverse Effects
Photosensitivity:
Demeclocycline, Doxycycline may produce
mild to severe reactions in the skin of treated
patients exposed to sunlight. This effect
appears to be as a result from the absorption
of UV radiation by the drug following
their accumulation in the skin. The activated
drug then emits energy at a lower frequency
that damage skin tissue leading to erythema.
128. Adverse Effects
Permanent staining of developing teeth
(Brownish discoloration) , hypoplasia of the
teeth, and retardation of bone growth can occur
if Tetracyclines are given after 4th month of
gestation or to children less than 8 years of age.
When given over long periods, use of these
drugs can result in a negative nitrogen balance,
which may lead to elevated blood urea nitrogen
(BUN) “ Nephrotoxicity”.
129. Adverse Effects
Hepatic toxicity develops in pregnant women
receiving high doses, especially if they were
experiencing pyelonephritis.
Expired Tetracyclines also cause Hepatotoxicity.
Vestibular problems (dizziness, nausea and
vomiting) occur with Minocycline or doxycycline
which concentrates in the ear and affects
function.
130. Tigecycline
It has a very broad spectrum.
Many tetracycline-resistant strains are susceptible to
Tigecycline. Methicillin-resistant staphylococci,
Vancomycin-resistant staphylococci, penicillin-resistant
streptococci, Vancomycin-resistant enterococci, multi-
drug resistant enterobacteriaceae, atypical bacteria
such as Rickettsiae, Chlamydia, and rapidly growing
mycobacteria.
Its tissue and intracellular penetration is excellent;
consequently its volume of distribution is large.
Elimination is primarily biliary.
131. Tigecycline
In addition to the tetracycline's adverse
effects, tigecycline's chief adverse effect is
nausea and occasionally vomiting.
Tigecycline is approved for I.V. treatment of
skin and skin-structure infections, abdominal
infections and community-acquired
pneumonia.
132. Antibacterial drugs targeting the 50 S
subunit (Macrolides and Ketolides)
Macrolides are named for their large lactone
rings. Attached to these rings are one or more
deoxy sugars.
Erythromycin (14 member lactone ring)
Clarithromycin (14 member lactone ring)
Azithromycin ( 15 member lactone ring)
Telithromycin (ketolides with 14 lactone ring).
134. Macrolides
They are proven to be especially important
in the treatment of pulmonary infections,
including Legionnaires’ disease.
These drugs display excellent lung tissue
penetration and they have intracellular
activity against legionella and other
microorganisms
135. Mechanism of Action
Macrolides are bacteriostatic agents that inhibit
protein synthesis by binding reversibly to the 50S
ribosomal subunits of sensitive bacteria.
They appear to inhibit the translocation step
wherein the newly synthesized peptidyl tRNA
molecule moves from acceptor (A) site on the
ribosome to peptidyl (P) or donor site.
Alternatively, Macrolides may bind and cause a
conformational change that terminates protein
synthesis by indirectly interfering with
transpeptidation and translocation.
136. Mechanism of Resistance
Efflux of drug by active pump mechanism
(e.g. Staphylococci, streptococci).
Production of methylase enzyme that
modifies the ribosomal target, leading to
decreased drug binding.
Hydrolysis of Macrolides by esterases
produced by enterobacteriaceae.
137. Erythromycin
Antibacterial activity:
Erythromycin is effective against Gram-
positive organism, in addition to the
Mycoplasma, Chlamydia, Rickettsiae,
Helicobacter & certain mycobacterium.
138. Pharmacokinetics
Erythromycin base is destroyed by acid, and
must be administered with enteric coating.
Stearates and esters are acid-resistant and
well absorbed (Esteolate is the best).
The absorbed drug is distributed widely
except cerebrospinal fluid.
it can cross the placental barriers.
These drugs are excreted mainly in the bile
(50X higher than blood).
139. Clinical Uses
They are the drugs of choice in the followings:
Corynebacterial infections (Diphtheria, Sepsis).
Chlamydia infections (Respiratory, Genital).
Mycoplasma infections (Pneumonia).
They are most useful alternative to Penicillins
in Gram-positive infections that are sensitive to
Penicillins (when there is allergy).
140. Adverse Effects
G.I.T. disturbances; N.V.D., mild epigastric pain, and
diarrhea (as a result of irritating effects on GIT).
Liver toxicity: acute cholestatic hepatitis (fever, Jaundice,
Impaired liver function) as hypersensitivity reactions( with
Esteolate only).
Hypersensitivity: fever, eosinophilia and rashes.
Inhibition of CYP450 isoenzymes: Erythromycin
metabolites can inhibit certain CYP450 isoenzymes in the
liver, & thus increase plasma concentration of numerous
drugs (oral anticoagulants , digoxin, and theophylline) that
are also metabolized by these hepatic enzymes.
They can also increase the concentration of terfenadine
causing serious cardiac arrhythmias.
141. Clarithromycin
It is a derivative of erythromycin, with similar spectrum
of activity and clinical uses, but more consistent
absorption and longer half life.
The spectrum of activity is the same as that of
erythromycin comprising most Gram-positive bacteria,
Mycoplasma, Chlamydia & some Gram-negative
bacteria.
Clarithromycin is more acid stable than erythromycin
and therefore is better absorbed. Almost complete oral
absorption occurs.
It is widely distributed throughout the body. It is 80%
bound to plasma proteins (alpha-1 acid glycoprotein).
Clarithromycin is eliminated both by renal excretion
(40%) and hepatic metabolism (60%).
142. Clinical Uses of Clarithromycin
1. Streptococcal Pharyngitis.
2. Sinusitis.
3. Community acquired pneumonia.
4. Atypical pneumonia.
5. Others: Clarithromycin has been used
successfully in Combination with Omeprazole
for eradication of Helicobacter pylori in PUD.
143. Azithromycin
Antibacterial activity:
Azithromycin is active against many aerobic & anaerobic
Gram-positive bacteria.
Because of its ability to cross the outer membrane of some
Gram-negative species (Unlike other Macrolides), it inhibits
a number of aerobic & anaerobic Gram-negative bacilli
(H.influenzae & certain enterobacteriaceae) .
Azithromycin is also active against intracellular pathogens
such as mycoplasma, Chlamydia and salmonella ( this is due
to great penetration of Azithromycin to the phagocytic cells"
macrophages and polymorphonuclear leukocytes”).
144. Pharmacokinetics
Azithromycin has an enhanced acid stability in the
stomach. Absorption is reduced by about 50% by the
presence of food in the stomach, and peak serum
levels are reduced by antacids containing (Al) or (Mg).
The initial decline in plasma levels is due to rapid
and extensive distribution of the drug into the
tissues including phagocytes. Drug in phagocytes is
transported to the sites of infection by chemotactic
mechanisms, and is then released, a process, that is
enhanced on exposure of the cell membrane to
bacteria.
145. Pharmacokinetics
It is widely distributed throughout the body.
High concentration is found in prostate,
pulmonary tissues, gastric mucosa, liver,
and gynecological tissues, even 4-5 days after
single dose.
The terminal elimination phase of Azithromycin
is due to hepatic metabolism, & biliary
excretion. The t ½ of this phase is about 40-60
hrs. This long t ½ allows once-daily dosing.
146. Therapeutic Uses
Upper and lower respiratory tract infections (Pharyngitis,
sinusitis, bronchitis, atypical pneumonia).
Skin and soft tissues infections.
Sexually transmitted diseases (genital Chlamydia infections).
(Single dose has been found to be very effective in treating these
infections, because single dose of Azithromycin produces high and
sustained levels in gynecological tissues up to 96 hours after
administration)
Eradication of Helicobacter pylori, in combination with anti-
PUD
147. Telithromycin
It is a semisyntheic 14-membered-ring
Macrolides (3-keto group is added), with broad
spectrum activity.
It has a mechanism of action similar to that of
Macrolides, but with a higher affinity for the
50S subunit due to its ability to bind additional
components of 50S. This higher affinity allows
the use of Telithromycin in treating infections
due to certain bacteria that are resistant to
Macrolides.
148. Telithromycin
Oral bioavailability, tissue and intracellular
penetration are good. Telithromycin is metabolized in
the liver and eliminated by a combination of biliary
and urinary routes of excretion. It is administered as
a once-daily dose.
Telithromycin is indicated for treatment of
respiratory tract infections, including community-
acquired pneumonia, chronic bronchitis, sinusitis and
Pharyngitis.
Like erythromycin, Telithromycin is a reversible
inhibitor of CYP450 and can be involved in numerous
drug-drug interactions.
149. Chloramphenicol
• It is a bacteriostatic broad-spectrum
antibiotic that is active against both
aerobic and anaerobic Gram-positive
and negative bacteria.
The most highly susceptible organisms
include H. influenzae, Neisseria
meningitides and some Bacteroides.
150. Chloramphenicol
The potential for serious toxicity has limited the
systemic use of Chloramphenicol. The drug is still
used occasionally in treatment of meningitis and
Rickettsial infections, but only when safer
alternatives are not available, as in the case of
resistance or serious drug allergy.
Chloramphenicol binds to 23S fraction of 50S
subunit and inhibits peptide bond formation,
apparently by occupying a site that interferes with
proper positioning of the aminoacyl moiety of
tRNA in the A site.
151. Pharmacokinetics
Absorption: mainly by Jejunum
Distribution: Diffuses to all fluids (including
CSF), cross the placenta.
Metabolism: Glucuronic acid
conjugation by Glucuronide transferase.
Excretion: Mainly enterohepatic
cycling, and Renal (Fraction).
152. Mechanism of Resistance
Resistance is mainly developed as a
result of spread of plasmid-encoded
acetyltransferases that inactivate the
drug.
153. Clinical Uses
Because of potential toxicity and bacterial
resistance, this drug is almost obsolete, except
for the following treatments:
Anaerobic infections (brain abscess, intra-
abdominal abscess caused by Bacteroides
fragilis)
Bacterial meningitis caused by H.influenzae.
Topical treatment of eye infections due to good
penetration to ocular tissues and aqueous
humor.
154. Adverse Effects
The mechanism underlying the toxicity appears to involve
inhibition of mitochondrial protein synthesis.
Hematological toxicity:
Dose related reversible depression of erythropoiesis.
Aplastic anemia, a rare but potentially fatal toxicity occurs via
an idiopathic mechanism that is unrelated to dose.
Baby Gray Syndrome in premature and newborns.
Accumulated and toxic level of Chloramphenicol occurs as a
result of lacking glucuronic acid conjugation, causing vomiting,
flaccidity, hypothermia, gray color respiratory distress and
metabolic acidosis.
Drug-drug interaction : Chloramphenicol is metabolic inhibitor
155. Lincosamides
The major Lincosamide in clinical use is
Clindamycin (chlorine substituted derivative
of lincomycin (semisynthetic).
Antibacterial activity:
Many Gram-positive are inhibited by
Clindamycin.
Clindamycin is highly effective against
anaerobic bacteria such as bacteroides.
156. Mechanism of action and Resistance
Mechanism of action:
Clindamycin inhibits peptide bond formation
through interactions with both the A site
(like Chloramphenicol) and/or the P site.
Mechanism of resistance:
Resistance to Clindamycin includes
methylation of the binding site on the 50S
ribosomal subunit and enzymatic inactivation
157. Pharmacokinetics
Clindamycin is absorbed from GIT rapidly and
incompletely (Kaopectate interferes with
absorption).
It penetrates well most tissues including bone.
It also concentrates within phagocytic cells,
which may offer a therapeutic advantage.
It does not penetrate the meninges but pass
the placental barrier.
It metabolizes in liver, and 90% of the
metabolites excreted in the urine.
158. Therapeutic Uses
Treatment of serious anaerobic infections
(Bacteroides)-mixed infections.
It is used in combination with aminoglycosides
to treat the penetrating wounds of the
abdomen; and infections originating in female
GUT (Septic abortion).
Treatment of deep seated infections
(e.g. Staphylococcal Osteomylitis), because it
can penetrate to bones.
It has excellent activity topically against
Corynebacterium acnes.
159. Adverse Effects
Antibiotic-associated colitis is caused by
toxigenic Clostridium difficile. This organism is
infrequently part of the normal fecal flora but is
selected out during administration of oral
Clindamycin. It grows to high number in the
sigmoid colon and secretes a necrotizing toxin
that produces pseudo- membranous colitis
(PMC). This potentially fatal complication must
be recognized promptly and treated with oral
Vancomycin (0.5 gm every 4-6 hours) and/or
Metronidazole which is also effective agent.
160. Adverse Effects
P.M.C. is characterized by mucosal
ulcerations, severe diarrhea, abdominal pain,
fever, & mucous and blood in stool.
This syndrome may occur several weeks
after cessation of drug.
For this reason, persons who develop
diarrhea during Clindamycin therapy should
discontinue use the drug and be closely
monitored for Superinfection and colitis.
161. Streptogramins
It is a combination of two
Streptogramin A (Dalfopristin) and
Streptogramin B (quinupristin) in a
30:70 ratio.
It is a rapidly bactericidal antibiotic for
the most multiple-drug-resistant strains.
162. Mechanism of Action
This combined product binds to the P
binding site of the 50 S bacterial ribosome,
forming stable complex. Thus, they
synergistically interrupt protein synthesis.
The type A Streptogramin binding causes a
conformational change to the 50S subunit,
which increases the activity of the type B
Streptogramin by a 100-fold. Streptogramin B
prevents the elongation of protein chains and
causes the release of incomplete peptides.
163. Pharmacokinetics
They are rapidly metabolized, with
half-lives of less than one hour.
It is excreted with its metabolites via
biliary system.
164. Therapeutic Uses
Its primary use is in the I.V. treatment of
infections caused by intracellular
Vancomycin-resistant Enterococcus faecium
(VRE), since this drug penetrates the
macrophages and polymorphonucleocytes
easily.
The infections caused by VRE include
pneumonia, meningitis, and endocarditis.
165. Adverse Effects
The principal toxicities are pain at the site of
infusion; arthralgia – myalgia syndrome, and
hyperbilirubinemia.
Because this antibiotic inhibits CYP3A4,
concomitant administration with other drugs
metabolize by the same CYP450 (Warfarin,
diazepam terfenadine, reverse transcriptase
inhibitors & cyclosporine) may lead to
potential toxicities of these drugs.
166. Linezolid (Oxazolidinones derivative)
It was introduce to combat resistant gram-
positive bacteria, such as Methicillin and
Vancomycin—resistant staphylococci,
streptococci and enterococci, in addition to
Vancomycin-resistant Enterococcus (VRE).
It is approved to be used in skin and soft
tissues infection and pneumonia caused by
the susceptible organisms
167. Mechanism of Action
Linezolid appears to work on the first step of
protein synthesis, initiation, unlike most other
protein synthesis inhibitors, which
inhibit elongation.It does so by preventing the
formation of the initiation complex, composed of
the 30S and 50S subunits of the ribosome, tRNA,
and mRNA. Linezolid binds to the 23S portion of
the 50S subunit (the center of peptidyl
transferase activity), close to the binding
sites of Chloramphenicol, lincomycin, and other
antibiotics.
168. Pharmacokinetics
Linezolid is 100% bioavailable after oral
administration and has a half-life of 4-6
hours. It is metabolized by CYP450
yielding two inactive metabolites that
are excreted by renal and non-renal
systems.
169. Adverse Effects
The principal toxicity of Linezolid is hematological-
reversible and mild. Thrombocytopenia, anemia and
neutropenia are the most common manifestations in
about 3% of treatment courses. Cases of optic and
peripheral neuropathy and lactic acidosis have been
reported with prolonged therapy of Linezolid.
It is neither an inducer nor an inhibitor of CYP450
enzyme but it is a weak, reversible inhibitor of MAO.
Enhancement of the pressor effects of
symapthomimitics, tyramine-containing foods, and
SSRIs were shown to occur.