Antibiotics definition, Early and modern history, classification of antibiotics, Mechanism of antibacterial action, bacterial cell and drug targets, penicillins nomenclature, degradation reactions of penicillins, medical classification of penicillins, SAR of penicillins, Mechanism of penicillins, Betalactamase inhibitors, Therapeutic uses of penicillins, toxicity of penicillins, Side effects of penicillins.
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation
VIRAL VACCINES
Since viruses are intracellular parasites they will grow only within other living cells.
Methods of viral vaccine production:
Cultivation of virus using free living animals
Fertile eggs
Tissue cultures
Tetracyclines,Biological sources,History,Sturctures,SAR,Mechanism of action,Spectrum of activity,Important structural units and the three acidity constants in the tetracycline molucule,amphoteric nature,epimerisation, chelation with metals,toxicity and uses.
Hello friends. In this PPT I am talking about Anti-viral drugs drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
This ppt deals with the sulfonamide group of drugs with classification, mechanism, spectrum, resistance, uses and adverse effects discussed in detail. It also discusses in detail about Cotrimoxazole
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
Broad Spectrum Antibiotic:Tetracycline,four cyclic rings,Physicochemical Properties,Classification-According to source and Based on Duration of action ,Mechanism of action-30S ribosomes ,Inhibit protein synthesis,Antimicrobial spectrum
Resistance
Adverse effects
Precautions,Uses by snehal chakorkar
penicillins - power point - History,mechanism of action,classification,chemis...Dr. Ravi Sankar
Antibiotics - Penicillin's - power point - History, mechanism of action, classification, chemistry, SAR, Nomenclature, uses, side effects- Medicinal chemistry.
Prof. P. Ravisankar M. Pharm., Ph.D.
HOD .,
Vignan Pharmacy college
vadlamudi- Guntur-A.P, India.
banuman35@gmail.com
Phone: 0 9059994000
0 9000199106
Brief historical background & classification of antibiotics.
Antibiotics are defined as chemical substances or compounds produced by various species of microorganisms such as bacteria and fungi, which in low concentrations destroy, kill or inhibit the growth of other species of microorganisms.
Antibiotics classification Antibiotics are usually classified based on their structure, Function and/or spectrum of activity.
VIRAL VACCINES
Since viruses are intracellular parasites they will grow only within other living cells.
Methods of viral vaccine production:
Cultivation of virus using free living animals
Fertile eggs
Tissue cultures
Tetracyclines,Biological sources,History,Sturctures,SAR,Mechanism of action,Spectrum of activity,Important structural units and the three acidity constants in the tetracycline molucule,amphoteric nature,epimerisation, chelation with metals,toxicity and uses.
Hello friends. In this PPT I am talking about Anti-viral drugs drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
This ppt deals with the sulfonamide group of drugs with classification, mechanism, spectrum, resistance, uses and adverse effects discussed in detail. It also discusses in detail about Cotrimoxazole
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
Broad Spectrum Antibiotic:Tetracycline,four cyclic rings,Physicochemical Properties,Classification-According to source and Based on Duration of action ,Mechanism of action-30S ribosomes ,Inhibit protein synthesis,Antimicrobial spectrum
Resistance
Adverse effects
Precautions,Uses by snehal chakorkar
penicillins - power point - History,mechanism of action,classification,chemis...Dr. Ravi Sankar
Antibiotics - Penicillin's - power point - History, mechanism of action, classification, chemistry, SAR, Nomenclature, uses, side effects- Medicinal chemistry.
Prof. P. Ravisankar M. Pharm., Ph.D.
HOD .,
Vignan Pharmacy college
vadlamudi- Guntur-A.P, India.
banuman35@gmail.com
Phone: 0 9059994000
0 9000199106
Brief historical background & classification of antibiotics.
Antibiotics are defined as chemical substances or compounds produced by various species of microorganisms such as bacteria and fungi, which in low concentrations destroy, kill or inhibit the growth of other species of microorganisms.
Antibiotics classification Antibiotics are usually classified based on their structure, Function and/or spectrum of activity.
Definition of Microbiology
Classification of Microorganism
Bacteria
Virus
Fungi
Parasite
Contribution of :-
Louis Pasteur
Antonie Philips van Leeuwenhoek
Robert Koch
Joseph Lister
Paul Ehrlich
Edward Jenner
Hans Christian Gram
Ernst Ruska
Alexander Fleming
Goodpasture
Karry B Mullis
1a. Prof. P. Ravisankar, Vignan Pharmacy College, Vadlamudi, Guntur, AP., Ind...Dr. Ravi Sankar
Antibiotics, characteristics of an antibiotic, Brief historical background of antibiotics, Modern History of antibiotics, Classification of antibiotics, four groups of beta-lactam antibiotics, Classification of Penicillins, Penicillinase resistant Penicillins, Narrow spectrum anti-staphylococcal Penicillins, Amino Penicillins, Nomenclature of Penicillins, Stereochemistry of Penicillins, Hydrolysis of Penicillins, SAR of Penicillins, Mechanism of Penicillins, Beta-lactamase inhibitors, Therapeutic uses of Penicillins, Penicillin advantages, and disadvantages, Hypersensitivity or allergic reactions of Penicillins.
The beginnings of pharmacy are ancient.
When the first person expressed juice from a succulent leaf to apply to a wound, this art was being practiced.
In the Greek legend, Asclepius, the god of the healing art, delegated to Hygieia the duty of compounding his remedies
HIGHLIGHTS IN THE HISTORY OF MICROBIOLOGY
Effects of Disease on Civilization
Infectious diseases have played major roles in shaping human history.
Bubonic Plague epidemic of mid 1300's, the "Great Plague", reduced population of western Europe by 25%. Plague bacterium was carried by fleas, spread from China via trade routes and poor hygiene. As fleas became established in rat populations in Western Europe, disease became major crisis.
Smallpox and other infectious diseases introduced by European explorers to the Americas in 1500's were responsible for destroying Native American populations. Example: In the century after Hernan Cortez's arrival in Mexico, the Aztec population declined from about 20 million to about 1.6 million, mainly because of disease.
Infectious diseases have killed more soldiers than battles in all wars up to World War II. Example: in U. S. Civil war, 93,000 Union soldiers died in direct combat; 210,000 died as a result of infections.
Until late 1800's, no one had proved that infectious diseases were caused by specific microbes, so there is no possibility of prevention or treatment.
002. Cephalosporins for students 2023 Prof. P. Ravisankar.pdfDr. Ravi Sankar
Cephalosporins, Why Cephalosporins? Advantages of cephalosporins over penicillin, Mechanism of action of cephalosporins, Classification of cephalosporins, Structures of some important cephalosporins and cephamycins, Oximinocephalosporins, SAR of cephalosporins,Hydrolytic reactions, degradation and stability of cephalosporins, Uses of cephalosporins, Comparison between 6-APA and 7-ACA and penam and cepham.
Tetracyclines are Octahydro napthacene derivatives which are bacteriostatic potent broad spectrum antibiotics and are the most widely prescribed form of antibiotic after penicillins.
TETRA means = four
CYCL means = hydrocarbon rings
INE means = derivation.
Tetracyclines are introduced 50 years ago as potent broad spectrum antibiotics.
They are biosynthesized form acetic acid and propionic acid units in microorganisms.
Finally, one of the best ways of reducing cancer is …..
Cancer prevention is an essential component of all cancer control plans because about 40 % of cancers are preventable.
Firstly…Public education campaigns are important in highlighting the dangers of smoking because possibly as many as 22 % (in the UK 30%) of cancers are caused by smoking.
Secondly, another 30% of cancers are diet-related. Decades of research have clearly shown that by living a healthy life, people can reduce the risk of developing the disease.
Screening tests help in finding Cancer earlier before developing any symptoms.
The benefits of eating high-fiber foods, fruit, and vegetables.
Epigallocatechin gallate, an antioxidant present in green tea, is another potential protective agent.
Finally, The new research funded by the UK and USA which aims to show the number of cancer cases could be prevented by known lifestyle and environmental factors,
like being a non-smoker, keeping a healthy weight, drinking less alcohol, eating a healthy balanced diet, and avoiding being exposed to certain infections or radiation.
Every country, regardless of resource level, can take steps to curb the cancer epidemic, save lives and prevent unnecessary suffering.
Finally, cancer prevention efforts should be preceded by a systematic planning process on cancer control.
NOVEL SEPARATION AND QUANTITATIVE DETERMINATION OF LEVOFLOXACIN, PRULIFLOXACI...Dr. Ravi Sankar
The core AIM of the present study is to develop a novel, rapid, precise and accurate RP-HPLC method for simultaneous separation and quantification of six fluoroquinolones OF LEVOFLOXACIN (LEVO), PRULIFLOXACIN (PRFX), GATIFLOXACIN (GATI), SPARFLOXACIN (SPAR), MOXIFLOXAXIN (MOXI) AND BALOFLOXACIN (BALO) for the the day to day analysis.
The author felt that a novel single method for separation and quantification of all the above said drugs on single chromatographic system without any minor changes in detection wavelength and mobile phase composition.
To develop rapid, sensitive and economical analytical method based on HPLC for separation and estimation of six fluoroquinolones pharmaceutical dosage forms.
To develop method with shorter run time and better sensitivity.
Reducing the solvent consumption to make it more eco-friendly.
Avoid the column damage by minimizing the buffer strength and pH of mobile phase than reported methods.
To validate the method for different parameters like Accuracy, Precision, Linearity, specificity, Robustness International Conference on Harmonization ICH Q2(R1) guidelines..
To apply the developed RP-HPLC method in the analysis of pharmaceutical formulations.
Analytical method development and validation of novel Levofloxacin, Pruliflox...Dr. Ravi Sankar
For the first time simple, selective, sensitive RP-HPLC method was developed for the separation and quantitative development of LEVO, PRFX, GATI, SPAR, MOXI and BALO relating to fluoroquinolone anti bacterials in pharmaceutical dosage forms. The most important advantage of developed method was that the 6 separate drugs can be determined on a single chromatographic system without modifications in detection wavelength and mobile phase by RP-HPLC. The chromatographic separation of the selected drugs was carried out on Welchrom C18 column consisting of 250 mm X 4.6 mm, 5 µm particle size utilizing mixture of 10 mM phosphate buffer (pH 3.1): Acetonitrile in the ratio of 70:30,v/v as mobile phase at the flow rate of 1mL/min with detection wave length at 293 nm by using UV spectrophotometric detector with total run time of 10 minutes and 3.613, 4.230, 4.707, 5.497, 5.880 and 6.253 minutes of retention time obtained for LEVO, PRFX, GATI, SPAR, MOXI and BALO respectively. All calibration curves for six drugs showed indicated linearity over a concentration range of 2-10 µg/mL. The results regarding to limit of detection (LOD) and limit of quantitation (LOQ) for LEVO, PRFX, GATI, SPAR, MOXI and BALO were found to be 0.116 µg/mL and 0.348 µg/mL; 0.152 µg/mL and 0.460 µg/mL; 0.084 µg/mL and 0.255 µg/mL; 0.186 µg/mL and 0.558 µg/mL, 0.162 and 0.493, 0.112 and 0.390 respectively. These results clearly show low values of LOD and LOQ. The said developed method was ultimately utilized for quantification of marketed formulation.
NOVEL SIMULTANEOUS SEPARATION AND QUANTITATIVE DETERMINATION OF FOUR SARTANS...Dr. Ravi Sankar
The core AIM of the present study is to develop a novel, rapid, precise and accurate RP-HPLC method for simultaneous separation and quantification of Hydrochlorothiazide along with four sartans Telmisartan(TELM), Losartan(LOSA), Olmesartan(OLME) and Valsartan(VALS).
To develop Novel methods for separation and quantification of all the above said drugs on single chromatographic system without any minor changes in detection wavelength and mobile phase composition.
Total quality management (TQM), and current Good Manufacturing Practice (cGMP...Dr. Ravi Sankar
TQM, cGMP, Introduction, Definition, Importance, TQM frame work, Key concepts (Principles) of TQM, specific steps in the cycle, Benefits of TQM, cGMP, principles of GMP, Improtance of GMP, why GMP established?, difference between GMP and cGMP, GMP and cGMP regulations, code of federal regulations.
Tetracyclines BY Dr. P. Ravisankar M. Pharm., Ph.D.Dr. Ravi Sankar
Tetracyclines by Dr. P. Ravisankar M. Pharm., Ph.D.
Definition
Introduction
Classification
Historical background
Sources
Chemistry
SAR of tetracyclines
Mechanism of action of tetracyclines
Spectrum of activity
Uses of tetracyclines
Side effects of tetracyclines
Dr. P. Ravisankar M. Pharm., Ph.D.
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Definition
Introduction
Classification
Structures,Functions,Deficiency,Diseases,Toxicity and uses.
Introduction to diuretics.
Therapeutic approaches.
Normal physiology of urine formation.
Classification of drugs .
Mechanism of action of Acetazolamide.
Mechanism of action of Thiazides.
Mechanism of action of Loop diuretics.
Mechanism of action of potassium sparing diuretics &aldosterone antagonists.
RIFAMPICIN [MEDICINAL CHEMISTRY] BY P.RAVISANKAR.Dr. Ravi Sankar
RIFAMPICIN SOURCE, STRUCTURES,MECHANISM OF ACTION,SAR,RIFAMYCINS, USES HOW T.B IS TREATED?
BY P. RAVISANKAR
VIGNAN PHARMACY COLLEGE
VADLAMUDI
GUNTUR,
ANDHRA PRADESH
INDIA.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
How STIs Influence the Development of Pelvic Inflammatory Disease.pptx
Antibiotics
1. ANTIBIOTICS
When antibiotics were first discovered they were called “wonder drugs”
Antibiotics (Literally ”against life”) according to Vuillemin.
Dr. PANCHUMARTHY RAVI SANKAR
M. Pharm, Ph.D.
Professor & HOD
Vignan pharmacy college,
Vadlamudi- 522 213 Guntur, A.P, India.
2. ““AntibioticsAntibiotics are defined as chemical substances or compoundsare defined as chemical substances or compounds
produced by various species of microorganisms such as bacteria andproduced by various species of microorganisms such as bacteria and
fungi, which in low concentrations destroy, kill or inhibit the growth offungi, which in low concentrations destroy, kill or inhibit the growth of
other species of microorganisms.”other species of microorganisms.”
Greek wordsGreek words anti = against ; bios = lifeanti = against ; bios = life
Vuillemin to define antibiotics literally meaning “against life”Vuillemin to define antibiotics literally meaning “against life”
In 1942 Waksman proposed the widely cited definition that “an antibiotic is a substanceIn 1942 Waksman proposed the widely cited definition that “an antibiotic is a substance
produced by microorganisms, which has the capacity of inhibiting the growth and even ofproduced by microorganisms, which has the capacity of inhibiting the growth and even of
destroying other microorganisms”.destroying other microorganisms”.
The word antibiotic came from the wordThe word antibiotic came from the word antibiosisantibiosis a term coined ina term coined in
18891889 by Louis Pasteur'sby Louis Pasteur's pupilpupil Paul VuilleminPaul Vuillemin which means a process bywhich means a process by
whichwhich life could be used to destroy lifelife could be used to destroy life..
However, by acylating it with various acid derivatives, more thanHowever, by acylating it with various acid derivatives, more than 50,00050,000
Semisynthetic penicillins have been made, of whichSemisynthetic penicillins have been made, of which less than 30less than 30 are currentlyare currently
used in medicine.used in medicine.
DEFINITION
:
3. Requirements for a substance to be considered as an antibioticRequirements for a substance to be considered as an antibiotic
-It should have a-It should have a wide spectrumwide spectrum of activity with theof activity with the ability to destroyability to destroy
or inhibitor inhibit many different species of pathogenic organisms.many different species of pathogenic organisms.
-It should be-It should be eliminated completelyeliminated completely from the body.from the body.
-It should-It should not produce adverse and side effectsnot produce adverse and side effects..
-It should-It should antagonizes the growthantagonizes the growth or survival of one or more speciesor survival of one or more species
of micro- organisms.of micro- organisms.
-It should be-It should be highly effectivehighly effective in low concentrations.in low concentrations.
-It should be-It should be nonallergenicnonallergenic to the host.to the host.
-It should-It should notnot eliminate theeliminate the normal floranormal flora of the host.of the host.
-It should be-It should be able to reachable to reach the part of the human body wherethe part of the human body where
the infection is occurring.the infection is occurring.
-It should be-It should be inexpensiveinexpensive andand easy to produceeasy to produce..
-It should be-It should be chemically-stablechemically-stable (have a long shelf-life).(have a long shelf-life).
-It is a product of metabolism (although it may be duplicated or even-It is a product of metabolism (although it may be duplicated or even
have been anticipated by chemical synthesis).have been anticipated by chemical synthesis).
4. HHistory of antibiotics can be described inistory of antibiotics can be described in two segmentstwo segments early history and modernearly history and modern
historyhistory..
Most important is the discovery of penicillin by SIRMost important is the discovery of penicillin by SIR Alexander Fleming.Alexander Fleming.
EARLY HISTORYEARLY HISTORY::
During ancient timesDuring ancient times ::
Long ago before 20Long ago before 20thth
century there was no proper treatment for diseases.century there was no proper treatment for diseases.
The diseases caused byThe diseases caused by Mycobacterium tuberculosis, Mycobacterium lepraeMycobacterium tuberculosis, Mycobacterium leprae were not identifiedwere not identified
..
Over 2,500Over 2,500 years ago , Chinese usedyears ago , Chinese used plants and moldy cheese usedplants and moldy cheese used to treat infected wounds.to treat infected wounds.
As early as 500 to 600 BC, molded curd of soybean was used in Chinese folk medicine to treatAs early as 500 to 600 BC, molded curd of soybean was used in Chinese folk medicine to treat
boils and carbuncles.boils and carbuncles.
The ancientThe ancient Egyptians used honey + lint (softEgyptians used honey + lint (soft cotton cloth covering and protecting wounds)+cotton cloth covering and protecting wounds)+lardlard
(melted fat of pigs) used as ointment(melted fat of pigs) used as ointment for dressing wounds.for dressing wounds.
EgyptiansEgyptians have often been foundhave often been found onions in body cavities of mummiesonions in body cavities of mummies. They used onions,. They used onions,
garlic and radish herb therapeutically. Infact they havegarlic and radish herb therapeutically. Infact they have anti-infective properties.anti-infective properties.
GreeksGreeks and Indians usedand Indians used mouldsmoulds and other plants to treat infections.and other plants to treat infections.
InIn Greece and Serbia, moldy breadGreece and Serbia, moldy bread was traditionally used to treat wounds andwas traditionally used to treat wounds and
infections.infections.
Warm soilWarm soil was used bywas used by RussiansRussians to cure infected wounds.to cure infected wounds.
Sumerian doctorsSumerian doctors gave patientsgave patients beer soup mixed with turtle shells and snakebeer soup mixed with turtle shells and snake
skinsskins..
Babylonian doctorsBabylonian doctors healed the eyes using a mixture ofhealed the eyes using a mixture of frog bile and sour milkfrog bile and sour milk ..
Sri Lankan armySri Lankan army usedused oil cake (sweetmeat)oil cake (sweetmeat) to serve as antibacterial.to serve as antibacterial.
5. TREATMENT OF INFECTIOUS DISEASES PRIOR TO ANTIBIOTICS.
Centuries earlier, humans had learned to use crude preparations for the
topical treatment of infections.
6. Modern HistoryModern History
Late 1800’s = Search for antibiotics began with the growing acceptance of the germ theory ofLate 1800’s = Search for antibiotics began with the growing acceptance of the germ theory of
disease(disease(Louis Pasteur was one of the first recognized physicians who observed that bacteria could beLouis Pasteur was one of the first recognized physicians who observed that bacteria could be
used to kill other bacteria)used to kill other bacteria)
1871 = The surgeon joseph lister found urine contaminated with1871 = The surgeon joseph lister found urine contaminated with
mould couldn't kill the bacteria.mould couldn't kill the bacteria.
1890’s = German doctors Rudolf emmerich, oscar low made1890’s = German doctors Rudolf emmerich, oscar low made
pyocyansepyocyanse from microbes. It was the first antibiotic usedfrom microbes. It was the first antibiotic used
in hospitals but the drug did not work.in hospitals but the drug did not work.
1909 =First modern chemotherapeutic agent1909 =First modern chemotherapeutic agent SALVARSANSALVARSAN for thefor the
treatment of syphilis.(Paul Ehrlich)treatment of syphilis.(Paul Ehrlich)
19281928 = Scottish bacteriologist= Scottish bacteriologist Sir Alexander Fleming discovered enzymeSir Alexander Fleming discovered enzyme
lysozyme and the antibiotic substance penicillin.lysozyme and the antibiotic substance penicillin.
1932 = Gerhard Domagk discovered1932 = Gerhard Domagk discovered ProntosilProntosil a prodrug.a prodrug.
1936 = Sulfanilamide the first synthetic sulfonamide in human medicine.1936 = Sulfanilamide the first synthetic sulfonamide in human medicine.
1940 =1940 = Invention of Modern Drug Discovery: Ehrlich & The Magic Bullet means
compound that selectively targets a disease causing organism while having
no negative effect on human tissue.no negative effect on human tissue.
1940 =First therapeutic use of penicillin by Floury.1940 =First therapeutic use of penicillin by Floury.
1944 = Selman waksman made Streptomycin from soil bacteria.1944 = Selman waksman made Streptomycin from soil bacteria.
1948 = Chlortetracycline.1948 = Chlortetracycline.
1957 = Nystatin (fungal infections)1957 = Nystatin (fungal infections)
1970’s = New 4-quinolones(pipemidic acid,oxolinic acid,cinoxacin)1970’s = New 4-quinolones(pipemidic acid,oxolinic acid,cinoxacin)
1980 =Norfloxacin, the first fluoroquinolone.1980 =Norfloxacin, the first fluoroquinolone.
1980 =Enroflocacin.1980 =Enroflocacin.
1998 =Smithkline Beecham patented Amoxicillin/clavulanate potassium tablets1998 =Smithkline Beecham patented Amoxicillin/clavulanate potassium tablets
the first sold antibiotic under the trade names of Amoxil and trimox.the first sold antibiotic under the trade names of Amoxil and trimox.
7. CLASSIFICATIONCLASSIFICATION:: Antibiotics are classified in many ways based on chemical structure, source, its spectrum of activity and MechanismAntibiotics are classified in many ways based on chemical structure, source, its spectrum of activity and Mechanism
of action (MOA).of action (MOA).
*Based on the chemical structure:*Based on the chemical structure: (Chemical classification):(Chemical classification):
1.1.β-lactam antibioticsβ-lactam antibiotics: Penicillin's, Cephalosporin's, carbapenams, monobactams.: Penicillin's, Cephalosporin's, carbapenams, monobactams.
2.2. Amino glycoside antibioticsAmino glycoside antibiotics: Streptomycin, Neomycin, Kanamycin, Gentamycin, Tobramycin, Amikacin.: Streptomycin, Neomycin, Kanamycin, Gentamycin, Tobramycin, Amikacin.
3.3. TetracyclinesTetracyclines:: Tetracycline, Chlortetracycline, Oxytetracycline, Doxycycline, Minocycline,Tetracycline, Chlortetracycline, Oxytetracycline, Doxycycline, Minocycline,
methacycline, meclocycline.methacycline, meclocycline.
4.4. Macrolide antibioticsMacrolide antibiotics:: ( Large conjugated double bonds in macrocyclic large lactone rings( Large conjugated double bonds in macrocyclic large lactone rings ::EryErythromycin, Oleandomycin.thromycin, Oleandomycin.
ClariClarithromycin,thromycin, AziAzithromycinthromycin,, RoxiRoxithromycin.thromycin.
55.. PolypeptidePolypeptide antibioticsantibiotics: Actinomycin, Bacitracin, Colistin, Polymyxin B, tyrothricin.: Actinomycin, Bacitracin, Colistin, Polymyxin B, tyrothricin.
6.6. Antifungal antibioticsAntifungal antibiotics :: Polyenes:Polyenes: a) 26 membered- ring polyenes Ex: Natamycin (Pimaricin).a) 26 membered- ring polyenes Ex: Natamycin (Pimaricin).
b) 38 membered macrocycles Ex: Amphotericin B, Nystatin, Natamycin.b) 38 membered macrocycles Ex: Amphotericin B, Nystatin, Natamycin.
Other antifungal antibiotics :Other antifungal antibiotics : Griseofulvin ( Spiro compound) isolated as curling factor inGriseofulvin ( Spiro compound) isolated as curling factor in
plants, obtained from fungus penicillium griseofulvum.plants, obtained from fungus penicillium griseofulvum.
7. Antitubercular antibiotics: Refamycins, Refampin(refampicin), refabutin, cycloserine, Capreomycin.7. Antitubercular antibiotics: Refamycins, Refampin(refampicin), refabutin, cycloserine, Capreomycin.
8. Antineoplastic antibiotics: Dactinomycin, Doxorubicin, daunorubicin, idarubicin, epirubicin, valrubicin8. Antineoplastic antibiotics: Dactinomycin, Doxorubicin, daunorubicin, idarubicin, epirubicin, valrubicin
Etoposide, Irinotecan, topotecan, Bleomycin ( glycopeptide antibiotic).Etoposide, Irinotecan, topotecan, Bleomycin ( glycopeptide antibiotic).
9.9. Lincomycin:Lincomycin: Clindamycin.Clindamycin.
10.10. MiscellaneousMiscellaneous: Chloramphenicol, Novobiocin, Mupirocin, Fusidic acid.: Chloramphenicol, Novobiocin, Mupirocin, Fusidic acid.
*Based on the source*Based on the source:: They are divided in toThey are divided in to
Natural antibioticsNatural antibiotics:: Penicillium chrysogenum-Penicillium chrysogenum---- Penicillin.--- Penicillin. Bacillus subtilisBacillus subtilis --- Bacitracin.--- Bacitracin.
Bacillus polymyxaBacillus polymyxa ------------- Polymyxin.------------- Polymyxin. Stryptomyces griseus-Stryptomyces griseus--- Streptomycin.-- Streptomycin.
Streptomyces aureofaciensStreptomyces aureofaciens ---Chlortetracyclines.---Chlortetracyclines. Stryptomyces erythraeusStryptomyces erythraeus -------Erythromycin-------Erythromycin
Streptomyces venezulae-Streptomyces venezulae------- Chloramphenicol.------ Chloramphenicol.
Semisynthetic antibioticsSemisynthetic antibiotics: These antibiotics are commercially synthesized by adding chemical compounds, amides etc., to the natural: These antibiotics are commercially synthesized by adding chemical compounds, amides etc., to the natural
antibiotics. In these the main part of the chemical structure is obtained from the micro-organisms which are then modified by adding variousantibiotics. In these the main part of the chemical structure is obtained from the micro-organisms which are then modified by adding various
chemical moieties as the side chain.chemical moieties as the side chain.
Ex:Ex: Ampicillin, Amoxacillin, Oxacillin, Cloxacillin, Dicloxacillin, Carbencillin. Methicillin.Ampicillin, Amoxacillin, Oxacillin, Cloxacillin, Dicloxacillin, Carbencillin. Methicillin.
**Spectrum ActivitySpectrum Activity::
Broad spectrumBroad spectrum: These antibiotics inhibit the growth of wide range (i.e. More than one species) of microorganisms. Some antibiotics can: These antibiotics inhibit the growth of wide range (i.e. More than one species) of microorganisms. Some antibiotics can
inhibit both Gram- positive and Gram-negative bacteria.inhibit both Gram- positive and Gram-negative bacteria.
EX:EX: Cephalosporins, Chloramphenicol, Tetracycline’sCephalosporins, Chloramphenicol, Tetracycline’s..
Narrow spectrumNarrow spectrum:: These antibiotics are effective mainly against a single species of microorganism eitherThese antibiotics are effective mainly against a single species of microorganism either
Gram +ve (or) Gram –ve bacteria. EX: -Gram +ve (or) Gram –ve bacteria. EX: - Bacitracin, Nystatin, PenicillinBacitracin, Nystatin, Penicillin..
8. Antibiotic activityAntibiotic activity :Based on their activity against different m.o’s they are divided in to:Based on their activity against different m.o’s they are divided in to
a. Antibacterial antibiotics:a. Antibacterial antibiotics: The chemotherapeutic agents which kill or inhibit the growth of bacteriaThe chemotherapeutic agents which kill or inhibit the growth of bacteria
are called antibacterial antibiotics. (penicillins, cephalosporins, tetracyclines, aminoglycosides)are called antibacterial antibiotics. (penicillins, cephalosporins, tetracyclines, aminoglycosides)
1.1. Bactericidal antibioticsBactericidal antibiotics :: These are more effective in killing harmful microorganisms particularlyThese are more effective in killing harmful microorganisms particularly
bacterialbacterial
species. (species. (Kill the bacteria directlyKill the bacteria directly)) ExamplesExamples are …..are …..
22. Bacteriostatic antibiotics:. Bacteriostatic antibiotics: These are effective in abolishing or preventing the growth ofThese are effective in abolishing or preventing the growth of
bacterial species. (bacterial species. ( stop the bacteria from growingstop the bacteria from growing ):):
EX: Tetracyclines, Chloramphenicol, Clindamycin.EX: Tetracyclines, Chloramphenicol, Clindamycin.
b.b. Antifungal antibioticsAntifungal antibiotics : Griseofulvin, Amphoterisin B, Nystatin.: Griseofulvin, Amphoterisin B, Nystatin.
c .c . Anthelmintic agentsAnthelmintic agents : Ivermectin.: Ivermectin.
d.d. Anticancer antibioticsAnticancer antibiotics : Bleomycin, Dactinomycin, Doxorubicin.: Bleomycin, Dactinomycin, Doxorubicin.
Penicillins and Cephalosporins Are Very cidal For Microbes
Penicillins Cephalosporins
Aminoglycosides
Vancomycin
Fluoroquinolones
Metronidazole
10. Beta-lactam antibiotics will be examined in fourBeta-lactam antibiotics will be examined in four
groups, includinggroups, including penicllinspenicllins, cephalosporins,, cephalosporins,
monobactams, and carbapenems.monobactams, and carbapenems.
The beta-lactam ring is joined to a five-memberedThe beta-lactam ring is joined to a five-membered
thiazolidine ring in penicillin,thiazolidine ring in penicillin,
Six-membered dihydrothiazine ring inSix-membered dihydrothiazine ring in
cephalosporins.cephalosporins.
In carbapenems, the beta-lactam ring is alsoIn carbapenems, the beta-lactam ring is also
joined to a five-membered ring, although it isjoined to a five-membered ring, although it is
carbocyclic.carbocyclic.
Monobactams have a monocyclic betalactamMonobactams have a monocyclic betalactam
structure, and the side sulfo-group is joined to astructure, and the side sulfo-group is joined to a
nitrogen atom.nitrogen atom.
All of these contain a four-membered beta-lactamAll of these contain a four-membered beta-lactam
ring, which is necessary for exhibiting antibacterialring, which is necessary for exhibiting antibacterial
activity.activity.
Four groups Beta-lactam antibiotics
11. Penicillin was discovered inPenicillin was discovered in 19281928 byby Alexander FlemingAlexander Fleming, who, who
noticed that one of his experimental cultures ofnoticed that one of his experimental cultures of staphylococcusstaphylococcus
was contaminated with mold, which caused the bacteria towas contaminated with mold, which caused the bacteria to
lyse. Since mold belonged to the familylyse. Since mold belonged to the family PenicilliumPenicillium, he named, he named
the antibacterialthe antibacterial substancesubstance penicillin.penicillin.
About a decade later, a group of researchers at OxfordAbout a decade later, a group of researchers at Oxford
University isolated a crude substance made up of a few low-University isolated a crude substance made up of a few low-
molecular substances, which were penicillins (molecular substances, which were penicillins (F, G, K, O, V,F, G, K, O, V,
XX).).
PENICILLINSPENICILLINS
13. Historical background of penicillinsHistorical background of penicillins
Alexander Fleming was born in Loudon, Scotland on 6 August,Alexander Fleming was born in Loudon, Scotland on 6 August,
1881 in a farming family.1881 in a farming family.
He carried on his schooling atHe carried on his schooling at regent streetregent street polytechnicpolytechnic after hisafter his
family moved to London in 1895.family moved to London in 1895.
He joinedHe joined St. Mary's medical schoolSt. Mary's medical school and became research assistantand became research assistant
to renowned Sir Almroth Wright, after he gotto renowned Sir Almroth Wright, after he got distinctiondistinction in 1906.in 1906.
He completed his degreeHe completed his degree (M.B.B.S.)(M.B.B.S.) withwith gold medalgold medal in 1908 fromin 1908 from
the University of London and lectured at St. Mart till 1914.the University of London and lectured at St. Mart till 1914.
He served asHe served as captaincaptain during theduring the World War IWorld War I and worked inand worked in
battlefield hospitals in France. After the war he returned to St. Marybattlefield hospitals in France. After the war he returned to St. Mary
in 1918 and got elected asin 1918 and got elected as Professor of bacteriology in 1928.Professor of bacteriology in 1928.
He discovered natural antiseptic enzyme in 1921, which he namedHe discovered natural antiseptic enzyme in 1921, which he named
lysozymelysozyme. This substance existed in tissues and secretions like. This substance existed in tissues and secretions like
mucus, tears and egg-white but it did not have much effect on themucus, tears and egg-white but it did not have much effect on the
strongly harmful bacteria.strongly harmful bacteria.
It was in 1928 when he observed while experimenting onIt was in 1928 when he observed while experimenting on influenzainfluenza
virusvirus that a common fungus inhibiting the growth of organism.that a common fungus inhibiting the growth of organism.
14. It was aIt was a Serendipitous observation(fortuitous accident)Serendipitous observation(fortuitous accident) i.ei.e
(happening by chance) in his laboratory in the basement of St.(happening by chance) in his laboratory in the basement of St.
Mary's Hospital in London ( now part of imperical college).Mary's Hospital in London ( now part of imperical college).
On Friday, September 28, in 1928, Fleming left the lid off of one ofOn Friday, September 28, in 1928, Fleming left the lid off of one of
his Petri dishes for several weeks, and a fungal spore landed on ithis Petri dishes for several weeks, and a fungal spore landed on it
(the culture became contaminated). After returning from vacation,(the culture became contaminated). After returning from vacation,
Fleming noticed that hisFleming noticed that his StaphylococcusStaphylococcus culture was contaminatedculture was contaminated
with this fungus but instead of throwing the Petri dish away, hewith this fungus but instead of throwing the Petri dish away, he
carefully examined it first.carefully examined it first.
There was an inhibited bacterial growth around the mould. FlemingThere was an inhibited bacterial growth around the mould. Fleming
concluded that the mould (fungal colony) was releasing aconcluded that the mould (fungal colony) was releasing a
antibacterial substance which was spreading into the surroundingantibacterial substance which was spreading into the surrounding
area where the bacterial colonies were dying. i.e. lysing the bacteria.area where the bacterial colonies were dying. i.e. lysing the bacteria.
He grew a pure culture and discovered that it was aHe grew a pure culture and discovered that it was a PenicilliumPenicillium
mould, now known to bemould, now known to be Penicillium notatum.Penicillium notatum.
Penicillium mould must be secreting an antibacterial substance,Penicillium mould must be secreting an antibacterial substance,
which he isolated first in crude form of the active substance andwhich he isolated first in crude form of the active substance and
named it as penicillin.named it as penicillin.
15. This newly discovered active substance(penicillin) was effectiveThis newly discovered active substance(penicillin) was effective
even when diluted up toeven when diluted up to 800800 times.times.
Unfortunately, the substance was alsoUnfortunately, the substance was also unstable and Fleming wasunstable and Fleming was
unableunable to isolate and purify the compoundto isolate and purify the compound. He therefore came to. He therefore came to
the conclusion that penicillin was too unstable to be used clinically.the conclusion that penicillin was too unstable to be used clinically.
Florey and Chain in 1938Florey and Chain in 1938 by using processes such asby using processes such as freeze-dryingfreeze-drying
and chromatographyand chromatography which allowed isolation of pure form ofwhich allowed isolation of pure form of
penicillins.penicillins.
Fleming, Florey, and Chain shared theFleming, Florey, and Chain shared the 1945 Nobel Prize1945 Nobel Prize for theirfor their
medicinal work on penicillin.medicinal work on penicillin.
In june 1942 availability of penicillin was just to treat 10 patients.In june 1942 availability of penicillin was just to treat 10 patients.
After fermentation research 2.3 million doses had been increased inAfter fermentation research 2.3 million doses had been increased in
U.S.U.S.
16. Commercial production of antibioticsCommercial production of antibiotics
The general scheme may be divided into six stepsThe general scheme may be divided into six steps
1.1. Preparation of a pure culture of the desired organism for use in inoculation of thePreparation of a pure culture of the desired organism for use in inoculation of the
fermentation medium.fermentation medium.
2.2. Fermentation, during which the antibiotic is formed.Fermentation, during which the antibiotic is formed.
3.3. Isolation of the antibiotic from the culture medium.Isolation of the antibiotic from the culture medium.
4.4. Purification.Purification.
5.5. Assays for potency, sterility, absence of pyrogens, and other necessary data.Assays for potency, sterility, absence of pyrogens, and other necessary data.
6.6. Formulation into acceptable and stable dosage forms.Formulation into acceptable and stable dosage forms.
1943 the mass production of penicillin began.
As the production increased the cost dropped
Correspondingly.
When penicillin was first available, 100,000
units sold for $20. currently, the same quantity
costs less than a penny.
17. Once the penicillin is released from the fungal cells, the compoundOnce the penicillin is released from the fungal cells, the compound
is isolated from the fermenter's contents and purified by specialis isolated from the fermenter's contents and purified by special
biochemical processes.biochemical processes.
Such commercial production results in more than 100,000,000Such commercial production results in more than 100,000,000
pounds of penicillin production per year.pounds of penicillin production per year.
Bulk production of pencillins
18. Biological sources of penicillinBiological sources of penicillin
The first naturally occurring benzyl penicillin (penicillin G is alsoThe first naturally occurring benzyl penicillin (penicillin G is also
referred to asreferred to as gold standard penicillingold standard penicillin ) was obtained by the) was obtained by the
fermentation of fungusfermentation of fungus Penicillium notatumPenicillium notatum..
At present it is obtained from a highly yielding strain calledAt present it is obtained from a highly yielding strain called
PenicilliumPenicillium chrysogenumchrysogenum and other penicillum species.and other penicillum species.
30 different biosynthetic penicillin's have been isolated from various30 different biosynthetic penicillin's have been isolated from various
strains ofstrains of Penicillium notatiumPenicillium notatium andand Penicillum chrysogenum.Penicillum chrysogenum.
22. Penicillin G (Benzylpenicillin)Penicillin G (Benzylpenicillin)
Penicillin G is also referred to asPenicillin G is also referred to as gold standard penicillingold standard penicillin..
Penicillin G is not acid resistant it is acid sensitive.Penicillin G is not acid resistant it is acid sensitive.
3 reasons for the acid sensitivity of penicillin G.3 reasons for the acid sensitivity of penicillin G.
11.. Ring strainRing strain. ( 4 membered betalactam ring + 5 membered thiazolidine ring) As a result penicillins. ( 4 membered betalactam ring + 5 membered thiazolidine ring) As a result penicillins
suffers large angle and torsional strains. Acid catalyzed ring opening relieves these strains by breakingsuffers large angle and torsional strains. Acid catalyzed ring opening relieves these strains by breaking
open the more highlyopen the more highly ββ –lactam ring.–lactam ring.
22.. Highly reactive corbonyl groupHighly reactive corbonyl group.. The resonance stabilization is impossible for theThe resonance stabilization is impossible for the ββ –lactam ring because–lactam ring because
of the increase in angle strain that would result in having a double bond withinof the increase in angle strain that would result in having a double bond within ββ –lactam ring. So the–lactam ring. So the
angle of theangle of the ββ –lactam ring constrained to 90–lactam ring constrained to 9000
. So the lone pair is localized on the N atom, and the. So the lone pair is localized on the N atom, and the
carbonyl group is more electrophilic than one would expect for a tertiary amide.carbonyl group is more electrophilic than one would expect for a tertiary amide.
Influence of the acyl side chainInfluence of the acyl side chain: Acyl group open up the lactam ring . So Penicillin G has a self-destruct: Acyl group open up the lactam ring . So Penicillin G has a self-destruct
mechanism built in its structure.mechanism built in its structure.
Benzylpenicillin is broken down by stomach acidBenzylpenicillin is broken down by stomach acid
and destroyed by staphylococcus penicillinase.and destroyed by staphylococcus penicillinase.
So it can be given by IV.So it can be given by IV.
Therapeutic uses:
Drugs of the penicillin group are effective for infections caused by Gram-positive bacteria
(streptococcus, pneumococcus, and others), spirochaetae, and other pathogenic microorganisms.
Drugs of this group are ineffective with respect to viruses, mycobacteria tuberculosis, fungi, and
the majority of Gram-negative microorganisms.
Benzylpenicillin is the drug of choice for infections caused by sensitive organisms. This includes streptococci
infections (except enterococci), gonococci, and meningococci that do not produce beta-lactam anaerobes.
Benzylpenicillin is used for croupous and focal pneumonia, skin infections, soft tissue and mucous membranes,
periotonitis, cystisis, syphilis, diphtheria, and other infectious diseases.
Benzyl group
N
S
COOH
H
CH3
CH3
HH
O
HNCH2C
O
23. N
S
COOH
H
CH3
CH3
HH
O
HNCH2C
O
O
It withdraws the electrons away
from the corbonyl oxygen and
reduce the tendency to act as a
nucleophile
Phenoxy methyl Penicillin ( Penicilln V)
•By placing electron with drawing group in the side chain which could draw
electrons away from the corbonyl oxygen and reduce its tendency to act as
a nucleophile.
•Penicillin- V has electro –ve oxygen on the acyl side chain with electron
withdrawing effect. It has more acid stability than penicillin G .
•It is more stable in acid in the stomach, so it can be given orally.
•Infact acid sensitivity can be solved by having an electron withdrawing group
on the Acyl side chain.
PENICILLIN- V
24. N
S
COOH
H
CH3
CH3
HH
O
HNCH2C
O
OCH3
OCH3
Strategy is putting
two ortho- methoxy
groups on the aromatic
ring.
Bulky groups
"Steric shields” can be added to penicillins to protect them from bacterial Betalactamase
(peicillinase) enzymes.
By placing bulky groups on the side chain, bulky groups can prevent the betalactamase or
penicillinase enzyme to Reach the beta lactamase or penicillinase active site.
Because of betalactamases bacteria can gain resistance to penicillin.
Betalactamases hydrolyse the ester link and open the pencillin. 1000 penicillin molecules
are hydrolysed per second.
Infact steric shield should not be too bulkey. If it is too bulkey it also prevents the penicillin
from attacking the transpeptidase target enzyme.
It should not be too small enough.. Methicillin is also not a ideal drug. Infact methicillin has
no electron withdrawing group on the side chain. Methicillin is acid sensitive and has to be
injected.
Penicillinase resistant penicillins
METHICILLIN
OC2H5
R Group
Nafcillin.
(Narrow spectrum Antistaphylococcal
penicillins)
Methicillin in USA not ued clinically
Methicillin produces Interstitial Nephritis (damages the kedney).
Nafcillin also some times produces Interstitial Nephritis.
it also Produces Neutropenia (Low level of Neutrophils ie,) white blood cells)
25. Isoxazoyl Penicillins
Penicillinase- resistant penicillins or β- lactamase- resistant penicillins
R1 R2
Oxacillin H H
Cloxacillin Cl H
Dicloxacillin Cl Cl
Flucloxacillin Cl F
N
S CH3
CH3
COOH
O
HN
O
N
O
CH3
R1
R2
H
H H
Bulkyand electron
withdrawing
group
Isoxazolyl ring
The incorporation of an isoxazolyl ring in to the penicillin side chain lead to orally active
compounds which were stable to β-lactamase enzymes of S. aureus.
The isoxazolyl ring acts as the steric shiels but it is also electron-withdrawing, giving the
structure acid stable.
The β-Lactamase resistant penicllins tend to be comparatively
lipophilic molecules that do not penetrate well into Gram –ve
bacteria.
α- acyl carbon could be part of an aromatic ( phenyl or
Naphthyl or heteroaromatic (e.g., 4-isoazoyl) system.
26. To sum up acid resistant penicillins would be the drugs of first choice against an infection.
If the bacteria proved resistance due to the presence of a Penicillinase enzyme
Penicillin resistant S. aureus therapy would be changed to penicillinase resistant penicillins.
Hydrophobic groups on the side chain(pen-G) favor gram +ve but Poor activity against gram-
ve.
Enhancement of gram -ve activity is found if hydrophilic Groups – NH2, - OH, -COOH are
attached to the alpha carbon from the carbonyl group on the side chain. Those Penicillins have
useful activity against gram +ve and gram -ve.
Hydrophilic groups on the side chain have little effect on Gram-positive activity (e.g.
penicillin T) or cause a reduction of activity (e.g. penicillin N)
However, they lead to an increase in activity against Gram-negative bacteria.
27. The acidic stability of the ampicillin also attributes the electron withdrawing character of the primary
amino group which prevents the hydrolysis of the β-lactum bond. It is susceptible to degradation by
β-lactamase enzymes. Hence it is given in Combination with inhibitors like sulbactum.
Hydrophobic groups on the side chain( Ex: penicillin G) favor activity against Gram-positive bacteria
Hydrophilic groups on the side chain have increase in activity against Gram –negative bacteria.
If the hydrophilic group is (NH2,OH,COOH group) attached to the carbon, alpha to the carbonyl group on the
side chain. All have an alpha hydrophilic group which aids the passage of these penicillins through the porins of
the Gram-ve Bacterial outer cell membrane.
Uses: Ampicillin and Amoxicillin HELPS to clear the Enterococci.
H – Haemophilus Influenzae.
E – Escherichia Coli.
L – Listeria monocytogenes.
P- Proteus.
S – Salmonella Typhi.
Amino Penicillins ( Ampicllin, Amoxicillin )
AMPICILLIN
N
S CH3
CH3
COOH
O
HN
O
C
H
H H
NH2
H
It is used for
bronchitis, pneumonia, dysentery,
salmonella, whooping cough,
pyelonephritis, endocarditis,
sepsis, and so on.
28. Amoxicillin (Amoxil) (p-hydroxy Ampicillin)
Amoxicillin is the very similar in structure like ampicillin, the only difference being
an extra phenol group on amoxicillin.
*similar spectrum of activity to penicillin G, but more active against Gram-ve bacteria
*Acid resistant due to the –NH2 group and therefore orally active.
*Non toxic, *Sensitive to β-lactamase (No shield).
---Can cause diarrhea due to poor absorption through the gut wall, is due to dipolar nature of the molecule
It has both free carboxylic acid and amino function. This problem can be solved by using a prodrug
Pivampicillin, talampicillin, bacampicillin are prodrugs of ampicillin. acyloxymethyl esters are used to mask the
-COOH groups. Its spectrum of activity is increased when administered with clavalunic acid.
Amoxicillin + clavalunic acid = Augmentin tablets.
Broad spectrum activity is associated with the
presence of an alpha hydrophilic group on the acyl side chain
of penicillin. Extra phenol group is present on amoxicillin.
If you compare with ampicillin, amoxicillin Is better absorbed
through gut wall.
Uses:
Bronchitis
Pneumonia
Typhoid
Enteric fever
Gonorrhoea
Urinary tract infactions.
N
S CH3
CH3
COOH
O
HN
O
C
H
H H
NH2
H
HO
29. Ampicillin synthesis:
Directly acylating 6-APA with phenylglycine chloride hydrochloride
Ampicillin
Amoxicillin synthesis:
The direct reaction of D-(-)-2-(4-hydroxyphenyl) glycine chloride hydrochloride with
trimethylsylil ester of 6-APA
Amoxicillin
30.
31. Nomenclature of Penicillins
Chemical abstract system(CAS):
According to this system penicillins are numbered starting from “S” atom.
Sulphur atom is assigned the 1st
position and the “N” atom is assigned number 4.
N
S
HH
O
N
S CH3
CH3
HH
O
COOH
1 2
3
4
56
7
(4-aza-1- thiabicyclo[3.2.0]heptane)-7-one
United States Pharmacopoeia (USP system):
The USP system of naming penicillins is the reverse of CAS.
According to this system the nitrogen atom is given the 1st
position and “S” atom is assigned the 4th
position.
N
S
HH
O 1
2
34
56
7
(4-Thia-1-azabicyclo[3.2.0]heptane)-7-one
penam(or)
As a derivatives of penicillanic acid:
According to this method of nomenclature penicillind consists of penicillanic acid ring system with
2,2-dimethyl and corboxyl groups as substutuents at positions 2 and 3 respectively.
2
3 H
As derivatives of penicillins (On the basis of Rgroup)
This is most trivalof all the naming system. In this system the entire 6-corbonylamino penicillanic acid
(6 corbonyl-APA) portion of the molecule is named as penicillin and the different penicills are
distinguished on the basis of the R group on the amino acyl side chain.
N
S CH3
CH3
HH
O
COOH
2
3 H
HNC
O
R
Thus when R is is a Benzyl group CH2
O
Benzyl penicillin (or) Penicillin G
CH2 Phenoxy methyl penicillin (penicillin- v)when R is Phenoxy methygroup
32. N
S CH3
CH3
HH
O
COOH
2
3 H
HNC
O
H2C 1
4
5
7
6
(2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicylo[3.2.0]heptane-2-corboxylate.
According to CAS
Penicillin G or benzyl penicillin nomenclature:
According to USP Pencicillin G chemical name is
N
S CH3
CH3
HH
O
COOH
2
3
H
HNC
O
H2C
1
4
5
7
6
(3S,5R,6R)-2,2-dimethyl-7-oxo-6-(2-phenylacetamido)-4-aza-1-thiabicylo[3.2.0]heptane-3-corboxylate.
33. The atoms composing the 6-aminopenicillanic acid are
biosynthetically derived from two amino acids, L-cysteine
and D-valine.
N
S
CH3
HH
O
COOH
2
3
HNC
O
R 1
4
5
7
6
According to CAS
According to USP
N
S CH3
CH3
HH
O
COOH
2
3
H
HNC
O
R
1
4
5
7
6
Stereochemical aspects of Penicillins
Cis stereochemistry
(cis orientation of hydrogens are very essenttial)
H
α - Configuration
β- Configuration
CH3
α - Configuration
The overall shape of the molecule is like a half-open book.
acyl amino group and corboxyl group are treans to one another.
3 chiral carbon atoms
are present
C- 3
C- 5
C- 6
3 chiral centres are present
C- 2
C- 5
C- 6
Trans orientation
of amino group
present at 7th
position
The carbon atom bearing the acylamino group (C-6) has the L-configuration, whereas the carbon to which the carbonyl group is attached has the D- configuration.
Thus, the acyl amino and corboxyl groups are trans to each other,wtih the former in theα and the latter in the orientation relative to the penam ring system.
The absolute stereochemistry of the penicillins is designated 3S:5R:6R.
N
S
O
2
3
1
4
5
7
6
penam
Azitidinone
(β- lactum)
Basic chemistry:β-lactum is fused with thiazolidine ring.
Thiazolidine ring.
34. Reactions: Hydrolysis of penicillins by hot and cold dilute mineral acidReactions: Hydrolysis of penicillins by hot and cold dilute mineral acid
35. There are also a variety of acylases that have been isolated from some bacteria, and
these enzymes cleave the acylamino sidechain of the antibiotic, a modification which also
36.
37. MEDICINAL CLASSIFICATION, CHEMICAL STRUCTURES, ANDMEDICINAL CLASSIFICATION, CHEMICAL STRUCTURES, AND
GENERIC NAMES OF PENICILLINS CURRENTLY AVAILABLEGENERIC NAMES OF PENICILLINS CURRENTLY AVAILABLE
38. 1.Natural1.Natural 1.Oral1.Oral 1.Narrow spectrum1.Narrow spectrum 1.Resistant1.Resistant toto 1.Acid1.Acid
Penicillin G Amoxycillin MethicillinPenicillin G Amoxycillin Methicillin betabeta lactamaselactamase stablestable
Peniciilin V Oxacillin Oxacillin Methicillin PenicillinGPeniciilin V Oxacillin Oxacillin Methicillin PenicillinG
2.Biosynthetic2.Biosynthetic Cloxacillin Dicloxacillin Oxacillin OxacillinCloxacillin Dicloxacillin Oxacillin Oxacillin
Penicillin G Dicloxacillin Nafcillin Cloxacillin CloxacillinPenicillin G Dicloxacillin Nafcillin Cloxacillin Cloxacillin
Penicillin V AmpicillinPenicillin V Ampicillin 2.Broad spectrum2.Broad spectrum Dicloxacillin AmpicillinDicloxacillin Ampicillin
Penicillin X AmpicillinPenicillin X Ampicillin 2.Non2.Non resistantresistant 2.Acid2.Acid
Penicillin FPenicillin F 2.Parenteral2.Parenteral AmoxycillinAmoxycillin toto betabeta lactamaselactamase unstableunstable
Penicillin K Penicillin GPenicillin K Penicillin G 3.Intermediate spectrum3.Intermediate spectrum Penicillin G TicarcillinPenicillin G Ticarcillin
3.Semisynthetic3.Semisynthetic Methicillin Penicillin G Penicillin V MethicillinMethicillin Penicillin G Penicillin V Methicillin
Oxacillin Nafcillin Penicillin v Ampicillin PiperacillinOxacillin Nafcillin Penicillin v Ampicillin Piperacillin
Cloxacillin CarbencillinCloxacillin Carbencillin 4.Extended spectrum4.Extended spectrum AmoxycillinAmoxycillin
Dicloxacillin Ticarcillin Carbencillin CarbencillinDicloxacillin Ticarcillin Carbencillin Carbencillin
Ampicillin TicarcillinAmpicillin Ticarcillin
Methicillin AzocillinMethicillin Azocillin 3838
39.
40.
41. N
S
COO
H
CH3
CH3
HH
O
HNCR
O
Thiazolidine
ring
β-Lactam
ring
Cis orientation of hydrogens
(stereochemistry) are essential
Bicyclic system
essential
Free corboxylate essential
Amide essential or
acylaminoside chain
essential
Strained β-lacturm
ring,which is necessary
for exhibiting
antibacterial activity
(The corboxylate ion binds
to the charged ammonium
ion of a lysine residue in the
binding site)
Sulfur is usual but not
essential
Presence of one
α-orientation and
one β-orientation
is essential for activity
Presence of N is essential
any modification upon
nitrogen it will results lack
of activity.
Highly reactive
ketonic group at
7th
position also
essential any
modification lack
of activity.
Amino group present
on the 6th
position
should be trans which
is very essential.
1
2
34
56
7
Bicyclic system confers further strainon
β-lactam ring. Greater the stran, the greater
the activity,but greater the instability of the
molecure to other factors.
6-Aminopenicillanic acid
The “R”group
determines the
Stability and
Improved spectrum
of activity and
Pharmacokinetic
advantages.
BASIC CHEMISTRY= β-LACTRUM RING + THIAZOLIDINE RING
STRUCTURE - ACTIVITY RELATION SHIP (SAR) OF PENICILLINS
GENERAL STUCTURE OF PENICILLIN OR PENICILLIN CORE STRUCTURE
PENICILLIN NUCLEUS OR BASIC STRUCTUREOF PENICILLIN
Valine
(amino
acid)
By
Prof. Ravisankar
Site of penicillinase action(break in beta lactum ring
(that bond is broken by betalactamase or penicillinase
Enzyme.(the bond b/n C and N is broken by ß-lactamase (or) penicillinase
enzme.
Cysteine
42. Key features of structure
1. β-lactam ring
a. "Lactam" is a word for any cyclic amide (the word "lactone" is used for
a cyclic ester)
b. a β-lactam means that the nitrogen is joined to the carbon which is beta
to the carbonyl
c. this creates strain in the ring, since it is a four membered ring
d. b-lactam becomes good acylating agent for active site serine of
penicillin binding
protein
2. Carboxylate:
a. Negatively charged at neutral pH
b. Anchors drug in active site pocket (positively charged)
3. Acylamide side chain:
a. Necessary for biological potency
b. Proper stereochemistry of attachment to ring essential for activity
c. Variation at side chain can dramatically affect biological activity against
various strains of bacteria
D. Common Early Penicillins
1. Penicillin G had to be administered parenterally, since it isn't acid stable.
2. Penicillin V has more acid stability, and can be administered orally
43. Penicillins are…. Simply substituted 6-aminopencillanic acid.
a group of antibiotics that contain 6-amino penicillanic acid side chain attached
to the 6-amino group.
•The penicillin nucleus is the chief structural requirement for biological activity.
•The side chain structure determines the many of the antibacterial and
pharmacological characterstics.
•The strained β-lactum ring is essential.
•Penicillin contains β-lactum ring is fused with thiazolidine ring.
•The free carboxylic acid is essential. The carbolated ion is binds to the charged
ammonium ion of lysine residue in the binding site.
•The bicyclic system is important. The greater the strain, the greater the activity.
•The acyl amino side chain is essential.
•Sulfur is usual but not essential.
•The cis- stereo chemistry of bicyclic ring with respect to the acyl amino side chain is
important.
•Oxidation of sulphur to a sulfone or sulfoxide will decrease the activity.
•The methyl groups at position 2 are essential.
•β- lactum corbonyl group at position “7” is must.
•The carboxylic acid is changed to an alcohol or ester activity is decreased.
•“N” at position 4 is must for antibacterial activity.
•Penicillin molecule contains a ‘3’ chiral carbon atome c-3,c-5,c-6. Disruption of
•These spacial arrangements results in loss of activity.
44. SAR of “R” group:SAR of “R” group:
C-6 amino west end substitution:C-6 amino west end substitution:
The design and development of the west-end substituents hasThe design and development of the west-end substituents has
been aimed at strengthening of activity, stability, resistance, absorption and distribution.been aimed at strengthening of activity, stability, resistance, absorption and distribution.
Placing the electron withdrawing group in the side chain which could draw electrons awayPlacing the electron withdrawing group in the side chain which could draw electrons away
from the carbonyl oxygen and reduce the tendency to act as a nucleophile and allows afrom the carbonyl oxygen and reduce the tendency to act as a nucleophile and allows a
greater stability and oral availability. Ex: penicillin V, Ampicillin.greater stability and oral availability. Ex: penicillin V, Ampicillin.
Stereic shields can be added to penicillin to protect them from bacterial β-lactamase enzymes.Stereic shields can be added to penicillin to protect them from bacterial β-lactamase enzymes.
By placing bulky groups on the side chain it prevent the penicillin from entering theBy placing bulky groups on the side chain it prevent the penicillin from entering the
penicillinase or β-lactamase active site.penicillinase or β-lactamase active site.
Infact if the stereic shield was too bulky then it also prevents the penicillin fromInfact if the stereic shield was too bulky then it also prevents the penicillin from
attacking the transpeptidase target enzyme, It should be ideal shield.attacking the transpeptidase target enzyme, It should be ideal shield.
but it should not be too small enough…but it should not be too small enough…
Ex: Methicillin.Ex: Methicillin.
Indeed Methicillin has no electron with drawing group on the side chain. It is acid sensitiveIndeed Methicillin has no electron with drawing group on the side chain. It is acid sensitive
and has to be injected.and has to be injected.
Incorporation of isoxazolyl ring in to the penicillin side chain lead to the development ofIncorporation of isoxazolyl ring in to the penicillin side chain lead to the development of
better penicillinase resistant agents. In fact isoxazolyl ring acts as the stereic shield but alsobetter penicillinase resistant agents. In fact isoxazolyl ring acts as the stereic shield but also
electron withdrawing group giving the structure acid stability.electron withdrawing group giving the structure acid stability.
Ex: Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin.Ex: Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin.
45. Broad spectrum activity is associated with the presence ofBroad spectrum activity is associated with the presence of αα-hydrophilic-hydrophilic
group on the acyl side chain of penicillin.group on the acyl side chain of penicillin.
Enhancement of Gram –ve activity is increased hydrophilic groupEnhancement of Gram –ve activity is increased hydrophilic group
(-NH(-NH22,OH,-COOH group), attached to the Carbon,,OH,-COOH group), attached to the Carbon,αα to the carbonyl groupto the carbonyl group
on the side chain. These penicillin's are having useful activity against bothon the side chain. These penicillin's are having useful activity against both
remove and gram-Vet bacteria are known as broad spectrum antibiotics.remove and gram-Vet bacteria are known as broad spectrum antibiotics.
EX: Ampicillin and Amoxicillin.EX: Ampicillin and Amoxicillin.
The spectrum of activity was further extended with introducing strongThe spectrum of activity was further extended with introducing strong
acidic group is attached to the carbonacidic group is attached to the carbon αα- to the carbonyl group on the side- to the carbonyl group on the side
chain.chain.
αα - carboxy penicillins are broad spectrum penicillins and wider range of- carboxy penicillins are broad spectrum penicillins and wider range of
gram-ve activity than ampicillin.gram-ve activity than ampicillin.
EX: Carbencillin,Ticarcillin.EX: Carbencillin,Ticarcillin.
The acylation of the ampicillin west-end amine functionality withThe acylation of the ampicillin west-end amine functionality with
certain polar groups leads to cyclic urea derivatives.certain polar groups leads to cyclic urea derivatives.
Urido penicillins have a urea functional group atUrido penicillins have a urea functional group at αα-position. In fact they-position. In fact they
are more active than the carboxy Penicillins against streptococci andare more active than the carboxy Penicillins against streptococci and
Haemophilus species. Presence of urea group gives improved penetrationHaemophilus species. Presence of urea group gives improved penetration
in to gram-ve species.in to gram-ve species.
EX: Azocillin, Mezlocillin, Piperacillin.EX: Azocillin, Mezlocillin, Piperacillin.
46. Plasma membrane
Peptidoglycan cell wall
(rigid coating around the membrane)
Lipopolysaccharide layer
(LPS)
Gram +ve Gram –ve
Thick Thin
One of the major difference between 2 types of bacteria is the amount of peptidoglycon
They have on the cell wall.
Gram +ve bacteria has a lot of peptidoglycon and this actually holds the gram stain in
That’s why it is gram +ve.
Gram –ve bacteria has a very thin layer of the peptidoglycon and gram stain leaks out
Cell membrane (or)
Outer membrane
Since the penicillin's inhibits peptidoglycon synthesis it is much better an attacking gram+ve bacteria such as
Staphylococci, and streptococci than gram –Ve bacteria like E-coli.
47. Beta-lactam antibiotics are relativelyBeta-lactam antibiotics are relatively
non-toxic to humans why?non-toxic to humans why?
One of the important point is penicillin is acting as a mimicOne of the important point is penicillin is acting as a mimic
for a D-Ala-D- Ala moiety, this provides another explanationfor a D-Ala-D- Ala moiety, this provides another explanation
for its lack of toxicity.for its lack of toxicity.
There is no D-Ala- D-Ala amino acids or D-Ala- D-AlaThere is no D-Ala- D-Ala amino acids or D-Ala- D-Ala
segments in any human protein. That’s why any of the body'ssegments in any human protein. That’s why any of the body's
serine protease enzymes does not recognize penicillin.serine protease enzymes does not recognize penicillin.
As a result penicillin is only selective for bacterialAs a result penicillin is only selective for bacterial
transpeptidase enzyme and ignored by the body’s own serinetranspeptidase enzyme and ignored by the body’s own serine
protease.protease.
48. Mechanism of action of penicillinsMechanism of action of penicillins
The primary mechanism of the action of beta-lactam antibiotics is the inhibition of synthesis ofThe primary mechanism of the action of beta-lactam antibiotics is the inhibition of synthesis of cell walcell wall ofl of
bacteria, which causes them to quickly die.bacteria, which causes them to quickly die.
The cell membrane protects bacteria cells from lysis, which can occur as a result of different osmotic pressuresThe cell membrane protects bacteria cells from lysis, which can occur as a result of different osmotic pressures
between the cytoplasm and the surrounding medium..between the cytoplasm and the surrounding medium..
The main component of bacterial cell membranes is a mixed polymer known asThe main component of bacterial cell membranes is a mixed polymer known as murein or peptidoglycanmurein or peptidoglycan..
Peptidoglycon is a long polysaccharide chain that is cross-linked with short peptides.Peptidoglycon is a long polysaccharide chain that is cross-linked with short peptides.
Polysaccharide chains are made up of two varying aminosugars—Polysaccharide chains are made up of two varying aminosugars—N-acetylglucosamineN-acetylglucosamine
andand N-acetylmuraminic acidN-acetylmuraminic acid. There are significant differences between Gram +ve and Gram –ve bacteria. The. There are significant differences between Gram +ve and Gram –ve bacteria. The
cell wall in Gram +ve bacteria consists ofcell wall in Gram +ve bacteria consists of 50-10050-100 peptidoglycon layers where as Gram –ve bacteria itpeptidoglycon layers where as Gram –ve bacteria it
consists onlyconsists only 2 layers2 layers..
Beta-lactam antibiotics specifically bind with a number of proteins of cytoplasmic membranes known asBeta-lactam antibiotics specifically bind with a number of proteins of cytoplasmic membranes known as
penicillin-binding proteins (PBP).penicillin-binding proteins (PBP).
The enzyme responsible for the cross-linking reaction is known as theThe enzyme responsible for the cross-linking reaction is known as the transpeptidase enzyme.transpeptidase enzyme.
Beta-lactam antibiotics must pass through the outer layer of the cell in order to get the desired PBP to theBeta-lactam antibiotics must pass through the outer layer of the cell in order to get the desired PBP to the
surface of the membrane.surface of the membrane.
About 30 enzymes are involved in the overall biosynthesis of cell wall but final cross linking reaction which isAbout 30 enzymes are involved in the overall biosynthesis of cell wall but final cross linking reaction which is
inhibited by penicillin. This leads to a cell wall framework that is no longer interlinked. As a result, the wallinhibited by penicillin. This leads to a cell wall framework that is no longer interlinked. As a result, the wall
becomes fragile and can no longer prevent the cell frombecomes fragile and can no longer prevent the cell from swelling and bursting.swelling and bursting.
It has been proposed thatIt has been proposed that penicillin has a conformation which ispenicillin has a conformation which is similar to the transition statesimilar to the transition state
conformation taken up by the D-Ala- D-Ala moiety during cross linking reactionconformation taken up by the D-Ala- D-Ala moiety during cross linking reaction. The enzyme. The enzyme
mistakes penicillin for D-Ala- D-Ala and binds to the active site.mistakes penicillin for D-Ala- D-Ala and binds to the active site.
Once bound, penicillin is subjected toOnce bound, penicillin is subjected to nucleophilic attack by serinenucleophilic attack by serine. The enzyme can attack the. The enzyme can attack the ββ- lactam rung- lactam rung
of penicillin and open it in the same way as it did with the peptide bond. However penicillin is a cyclic and asof penicillin and open it in the same way as it did with the peptide bond. However penicillin is a cyclic and as
a result the molecule isa result the molecule is not split in twonot split in two and nothing leaves the active site.and nothing leaves the active site.
49. Transpeptidase connects the little peptide chains perpendicular to the NAM chains.Transpeptidase connects the little peptide chains perpendicular to the NAM chains.
Without the grid the rapidly growing bacteria can’t maintain the strong cell wall.Without the grid the rapidly growing bacteria can’t maintain the strong cell wall.
There is a high pressure inside the cell i.e. 10-20 atm. pressure which means if the cell wall isThere is a high pressure inside the cell i.e. 10-20 atm. pressure which means if the cell wall is
not present, the rigid coating bacteria can swell and burst.not present, the rigid coating bacteria can swell and burst.
β – lactam antibiotics like penicillins act by inhibiting the transpeptidase (or) PBPs byβ – lactam antibiotics like penicillins act by inhibiting the transpeptidase (or) PBPs by
covalently bonding to the serine residues within the active sites and prevent the cell wallcovalently bonding to the serine residues within the active sites and prevent the cell wall
synthesis.synthesis.
50. (Peptidoglycan cell wall)
N-acetylglucosamine
N-acetylmuramic acid
Transpeptidase located
within the cell membrane
are responsible for
cross linking the
Peptidoglycon chains
Transpeptidases
(Penicillin Binding Proteins)
In order to make the rigid grid,
There is an enzyme called
Transpeptidase, which
connects
the Little peptide strings
perpendicular to the
NAM and NAG chains.
Cell membrane
PBP’S (or) transpeptidase help to build
Or construct maintain the peptidoglycon
Layer.
54. Microbial resistance toMicrobial resistance to ββ-lactam antibiotics-lactam antibiotics like penicillins, cephalosporins occurslike penicillins, cephalosporins occurs
mainlymainly due to the production of an enzyme known asdue to the production of an enzyme known as ββ-lactamases.-lactamases.
ββ-lactamases act by breaking the-lactamases act by breaking the ββ-lactam ring by catalyzing the hydrolysis of-lactam ring by catalyzing the hydrolysis of ββ--
lactum ringlactum ring, which results in the loss of antibacterial property of antibiotics. Thus, which results in the loss of antibacterial property of antibiotics. Thus
micro-organisms exhibit resistance.micro-organisms exhibit resistance.
ββ-lactamase inhibitors are-lactamase inhibitors are ββ-lactam structures that have negligible antibacterial-lactam structures that have negligible antibacterial
activity but inhibitactivity but inhibit ββ-lactamases-lactamases..
They can be administered along with penicillinsThey can be administered along with penicillins to protect them fromto protect them from ββ-lactamases-lactamases
and broaden(increase) their spectrum of activityand broaden(increase) their spectrum of activity..
ββ-lactamase inhibitors such as-lactamase inhibitors such as Clavulanic acid, Sulbactam, Tazobactum act asClavulanic acid, Sulbactam, Tazobactum act as
suicide substrates forsuicide substrates for ββ-lactamase enzymes.-lactamase enzymes.
Suicide substrates are agents which are converted to highly reactive species whenSuicide substrates are agents which are converted to highly reactive species when
they ungergo an enzyme-catalyzed reaction. They formthey ungergo an enzyme-catalyzed reaction. They form covalent bonds to thecovalent bonds to the
enzyme and inhibit irreversiblyenzyme and inhibit irreversibly..
55. The agents Clavalunic acid, sulbactam and tazobactam have also been developed as
β-lactamase inhibitors.
Ampicillin + Sulbactum = unasyn.
Amoxycillin + Clavulanic acid = Clavulin
Augmentin
Ticarcillin + Clavulanic acid = Timentin
Piperacillin + Tazobactam = Tazocin (or)
zosyn
Allow the “real” drug to get through to bind to the PBP’s
Regain gram negative spectrum of activity otherwise lost due
to β-lactamase production
56. Clavulanic acid:Clavulanic acid:
clavalunic acid was isolated from streptomyces clavuligerus by Bechams inclavalunic acid was isolated from streptomyces clavuligerus by Bechams in
1976.1976.
It has weak and unimportant antibiotic activity, but it is powerful andIt has weak and unimportant antibiotic activity, but it is powerful and
irreversible inhibitor of most β-lactamases and as such it is now usedirreversible inhibitor of most β-lactamases and as such it is now used
in combination with penicillins such as amoxicillinin combination with penicillins such as amoxicillin( Augmentin)( Augmentin)
The structure of clavulanic acid was the first example of a naturally occuringThe structure of clavulanic acid was the first example of a naturally occuring
β-lactam ring that was not fused to a sulfur-containing ring.β-lactam ring that was not fused to a sulfur-containing ring.
It is fused instead to an oxazolidine ring structure.It is fused instead to an oxazolidine ring structure.
ESSENTIAL REQUIREMENTS FORESSENTIAL REQUIREMENTS FOR ββ-lactamase inhibition are:-lactamase inhibition are:
StrainedStrained ββ-lactam ring.-lactam ring.
Enol ether.Enol ether.
The double bond of the enol ether has the Z configuration(Activity is reducedThe double bond of the enol ether has the Z configuration(Activity is reduced
but not eliminated if the double bond is E)but not eliminated if the double bond is E)
No substitution at C-6No substitution at C-6
R- Stereochemistry at positions 2 and 5.R- Stereochemistry at positions 2 and 5.
Carboxylic acid group.Carboxylic acid group.
57.
58.
59. Resistance to the B-lactam Antibiotics
1. Differences in PBP’s
- Decreased affinity of the PBP for the binding of the Abx
- Increased production / concentration of PBP’s produced
2. B-lactamase production
- Spectrum of activity of various B-lactamases
- Concentration of B-lactamases produced
3. Decreased ability to penetrate to the PBP target
- Primarily due to the LPS layer of gram –ve bacteria
60. Penicillin’s may be used to treat infections such as urinary tract infections.Penicillin’s may be used to treat infections such as urinary tract infections.
Septicaemia, meningitis, intra-abdominal infection, respiratory infections, ear,Septicaemia, meningitis, intra-abdominal infection, respiratory infections, ear,
nose and throat infections.nose and throat infections.
Skin and Soft tissue infections. Examples of infectious micro organisms (bacteria)Skin and Soft tissue infections. Examples of infectious micro organisms (bacteria)
that may respond to penicillin therapy includethat may respond to penicillin therapy include
* Streptococcal infections* Streptococcal infections
* Pneumococcal infections* Pneumococcal infections
* Meningococcal infections* Meningococcal infections
* Gonorrhoea* Gonorrhoea
* Syphilis* Syphilis
* Diphtheria* Diphtheria
* Tetanus and gas gangrene* Tetanus and gas gangrene
DRUG OF CHOICE for *Anaerobic anthrax*DRUG OF CHOICE for *Anaerobic anthrax*
* Actinomycosis* Actinomycosis
* Trench mouth* Trench mouth
* Rat bite fever* Rat bite fever
* Listeria monocytogenes* Listeria monocytogenes
* Pasteurella multocida* Pasteurella multocida
61. Penicillins are available only with a prescription. Penicillin’s are useful againstPenicillins are available only with a prescription. Penicillin’s are useful against
infections in many parts of the body, including the mouth and throat, skin andinfections in many parts of the body, including the mouth and throat, skin and
soft tissue, tonsils, heart, lungs, and ears. For example, dentists often prescribesoft tissue, tonsils, heart, lungs, and ears. For example, dentists often prescribe
penicillin to prevent infections after dental surgery.penicillin to prevent infections after dental surgery.
Biosynthetic penicillins are important in chemotherapy. They are used inBiosynthetic penicillins are important in chemotherapy. They are used in
treating streptococcal sore throat, tonsillitis, pneumococcal pneumonia,treating streptococcal sore throat, tonsillitis, pneumococcal pneumonia,
endocardities caused by some streptococci, syphilis, gonorrhoea, meningococcalendocardities caused by some streptococci, syphilis, gonorrhoea, meningococcal
infections and infections that are caused by some anaerobic organisms.infections and infections that are caused by some anaerobic organisms.
The drug Augmentin, for example, contains a combination ofThe drug Augmentin, for example, contains a combination of
amoxicillin(500mg) and a β-lactamase inhibitor, clavulanic acid (125mg)amoxicillin(500mg) and a β-lactamase inhibitor, clavulanic acid (125mg) usedused
in the treatment of Feverish patients with neutropenia from cancerin the treatment of Feverish patients with neutropenia from cancer
chemotherapy.chemotherapy. It is also useful in treating the sinusitis. Animal/human biteIt is also useful in treating the sinusitis. Animal/human bite
wounds, otitis media in children.wounds, otitis media in children.
There are several types of penicillins, each used to treat different kinds ofThere are several types of penicillins, each used to treat different kinds of
infections.infections.
These drugs will not work for, flu, and other infections caused by viruses.These drugs will not work for, flu, and other infections caused by viruses.
62. Adverse/toxic effects of penicillins:-
Although most penicillins are safe for the majority of people, some people may
experience side effects. Once an individual is allergic to one penicillin, he or
she is most likely allergic to all of the penicillins.
The most serious allergic reaction is anaphylaxis that can be fatal which is not
treated properly.
a severe allergic reaction that can cause skin rash, itching, difficulty breathing,a severe allergic reaction that can cause skin rash, itching, difficulty breathing,
shock, and unconsciousness.shock, and unconsciousness.
An early sign of anaphylaxis is a feeling of warmth and flushing. If any ofAn early sign of anaphylaxis is a feeling of warmth and flushing. If any of
these occurs, the medicine should be stopped and emergency help soughtthese occurs, the medicine should be stopped and emergency help sought
immediately.immediately.
Anaphylactic shock occurs more frequently after parenteral administration butAnaphylactic shock occurs more frequently after parenteral administration but
can occur with oral use.can occur with oral use.
63. After 7 days this allergy occurred her after penicillin has been
taken for throat Infection. That is Late hypersensityvity.
65. Less common side effects of penicillins are
1. Nausea 2. Diziness 3. Head ache 4. skin rashes 5. Bronchospasm 6. vasculitis 7.
inflammation of blood vessels 8. constriction of the airways of the lungs 9. fever
10. Angioedema or swelling of lips, face and tongue.
Other most common side effects are mild diarrhoea, vomiting, headache, vaginal
itching and discharge, sore mouth or tongue, or white patches in the mouth or on
the tongue. These problems usually go away as the body adjusts to the drug and do
not require medical treatment unless they continue or they are bothersome.
Occasionally, certain types of penicillin may cause the tongue to darken or
discolour. This condition is temporary and will go away when the medicine is
stopped.
Effect on GITEffect on GIT: Broad spectrum penicillins like Ampicillin, when administered: Broad spectrum penicillins like Ampicillin, when administered
orally, alters the bacterial flora in the intestines and leads to GIT disturbances likeorally, alters the bacterial flora in the intestines and leads to GIT disturbances like
diarrhoea .diarrhoea .
On rare occasions some types of penicillin may cause severe abdominal or stomachOn rare occasions some types of penicillin may cause severe abdominal or stomach
cramps, pain, or bloating or severe or bloody diarrhoea. Other rare side effectscramps, pain, or bloating or severe or bloody diarrhoea. Other rare side effects
include fever, increased thirst, severe nausea or vomiting, unusual tiredness orinclude fever, increased thirst, severe nausea or vomiting, unusual tiredness or
weakness, weight loss, seizures, or unusual bleeding or bruising .weakness, weight loss, seizures, or unusual bleeding or bruising .
Over dosage/Acute ToxicityOver dosage/Acute Toxicity - Acute oral penicillin overdoses are unlikely to- Acute oral penicillin overdoses are unlikely to
cause significant problems other than GI distress, but other effects are possible .Incause significant problems other than GI distress, but other effects are possible .In
humans, very high dosages of parenteral penicillin’s, especially in patients withhumans, very high dosages of parenteral penicillin’s, especially in patients with
renal disease, have induced CNS effects.renal disease, have induced CNS effects.
66. Hypersensitivity or allergic reactions :
Hypersensitivity to penicillin’s is caused by the degradation
products of penicillins. The degradation products of
penicilloic acid, sodium benzyl penicilloate (of β-lactum
ring) binds ie combines to serum proteins initiating an IgE
and initiates the IgE mediated inflammatory reactions
It occurs in about 5-8% of the patients and according to
estimation, 300-500 people have been dieing each year form
penicillin induced anaphylaxis.
Hypersensitivity reactions are classified into
A) Immediate Hypersensitivity
b) Accelerated Hypersensitivity
C) Late Hypersensitivity
67. A)A) Immediate hypersensitivityImmediate hypersensitivity:: -- This occursThis occurs within 20 minwithin 20 min. of parenteral. of parenteral
administration of penicillin and is characterized by the prurities, skinadministration of penicillin and is characterized by the prurities, skin
rashes, wheezing, rhinitis, sneezing.rashes, wheezing, rhinitis, sneezing.
These reactions are transformed in to anaphylaxis (extreme from ofThese reactions are transformed in to anaphylaxis (extreme from of
immediate hypersensitivity reaction) that it is characterised by hypotensiveimmediate hypersensitivity reaction) that it is characterised by hypotensive
shock, angioneurotic oedema, choking, loss of consciousness and finallyshock, angioneurotic oedema, choking, loss of consciousness and finally
death.death.
Serious anaphylaxis reactions require immediate emergency treatment withSerious anaphylaxis reactions require immediate emergency treatment with
ephedrine, oxygen, IV steroids and airway management, includingephedrine, oxygen, IV steroids and airway management, including
intubations should also be administered as indicated.intubations should also be administered as indicated.
B)B) Accelerated HypersensitivityAccelerated Hypersensitivity:: - It occurs- It occurs within few hourswithin few hours afterafter
penicillin has been administered. Accelerated hypersensitivity reactions arepenicillin has been administered. Accelerated hypersensitivity reactions are
characterized by skin rashes, fever, urticaria, angioneurotic oedema. Deathcharacterized by skin rashes, fever, urticaria, angioneurotic oedema. Death
is a rare consequence.is a rare consequence.
c)c) Late HypersensitivityLate Hypersensitivity:: It occursIt occurs after 72 hoursafter 72 hours after penicillin hasafter penicillin has
been administered. This reaction is mediated by IgE and IgM antibodiesbeen administered. This reaction is mediated by IgE and IgM antibodies
and manifested byand manifested by utricaria, skin rashes similar to measles, localutricaria, skin rashes similar to measles, local
inflammation, serum sickness and coomb’s positive haemolytic anaemiainflammation, serum sickness and coomb’s positive haemolytic anaemia
68. Penicillin's advantages and disadvantagesPenicillin's advantages and disadvantages
Penicillin's disadvantagesPenicillin's disadvantages::
Acid liability - most of these drugs are destroyed by gastric acid.Acid liability - most of these drugs are destroyed by gastric acid.
Short duration of action - because of this short half-life, the penicillin's must be at shortShort duration of action - because of this short half-life, the penicillin's must be at short
intervals, usually every 4 hours.intervals, usually every 4 hours.
Lack of activity against most gram-negative organisms.Lack of activity against most gram-negative organisms.
Drug hypersensitivity - about 10 % of population has allergy.Drug hypersensitivity - about 10 % of population has allergy.
Many patients experience GI upset.Many patients experience GI upset.
Painful if given intramuscularly.Painful if given intramuscularly.
penicillin's advantagespenicillin's advantages::
Bactericidal against sensitive strains.Bactericidal against sensitive strains.
Relatively nontoxic.Relatively nontoxic.
Have excellent tissue penetration.Have excellent tissue penetration.
Efficacious in the treatment of infections.Efficacious in the treatment of infections.
Relatively inexpensive in comparison with other antibiotics.Relatively inexpensive in comparison with other antibiotics.
Newer penicillin's are resistant to stomach acid, such as penicillin v, or have a broaderNewer penicillin's are resistant to stomach acid, such as penicillin v, or have a broader
spectrum, such as Ampicillin and Amoxicillin.spectrum, such as Ampicillin and Amoxicillin.
69. Key pointsKey points
Penicillins have aPenicillins have a bicyclic structurebicyclic structure consisting of aconsisting of a ββ-lactam ring fused to a-lactam ring fused to a
Thiazolidine ring.Thiazolidine ring.
The strainedThe strained ββ-lactam ring reacts irreversibly with the transpeptidase enzyme-lactam ring reacts irreversibly with the transpeptidase enzyme
responsible for the final cross-linking of the bacterial cell wall.responsible for the final cross-linking of the bacterial cell wall.
Penicillin can be made more resistant to acid conditions by incorporating anPenicillin can be made more resistant to acid conditions by incorporating an
electronelectron withdrawing groupwithdrawing group into the acyl side chain.into the acyl side chain.
Penicillin analoguesPenicillin analogues can be prepared by fermentation or by a semi-syntheticcan be prepared by fermentation or by a semi-synthetic
synthesis from 6-aminopenicillanic acid. Variation of the penicillin structure issynthesis from 6-aminopenicillanic acid. Variation of the penicillin structure is
limited to the acyl side chain.limited to the acyl side chain.
Steric shieldSteric shield can be added to penicillins to protect them from bacterialcan be added to penicillins to protect them from bacterial ββ--
lactamase enzymes.lactamase enzymes.
Broad spectrum activityBroad spectrum activity is associated with the presence of anis associated with the presence of an αα-hydrophilic-hydrophilic
group on the acyl side chain of penicillins.group on the acyl side chain of penicillins.
Ureidopenicillins are the newest class of broad-spectrum penicillins and have aUreidopenicillins are the newest class of broad-spectrum penicillins and have a
urea functional group at the alpha position.urea functional group at the alpha position.