The document discusses various classes of anticancer drugs including cytotoxic drugs derived from natural sources like plants and microbes. It focuses on the mechanisms of action and classification of antitumor antibiotic drugs derived from Streptomyces bacteria. Specifically, it describes the structures, mechanisms involving DNA intercalation and inhibition of topoisomerases, and clinical uses of important anthracycline antibiotics like doxorubicin, daunorubicin and actinomycin antibiotics like dactinomycin and mitomycin C.
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.
Anticancer Drug, also called Anti-Neoplastic drug, that is effective in the treatment of malignant, or cancerous, disease. There are several major classes of anticancer drugs; these include Alkylating Agents, Anti-metabolites, Plant Alkaloids and Hormones.
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.
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
Shortened description of STATURAL ACTIVITY RELATIONSHIP OF ANTIMETABOLITES & its MECHANISM OF ACTION - ANTINEOPLASTIC AGENTS (folate antagonist, purine antagonist & pyridine antagonist)(MEDICINAL CHEMISTRY)
quite useful for B PHARMACY & Pharm D Students.
Aminoglycosides(medicinal chemistry by p.ravisankar)Dr. Ravi Sankar
Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
Definition
Anticancer, or antineoplastic, drugs are used to treat malignancies, or cancerous growths. Drug therapy may be used alone, or in combination with other treatments such as surgery or radiation therapy.
Purpose
Anticancer drugs are used to control the growth of cancerous cells. Cancer is commonly defined as the uncontrolled growth of cells, with loss of differentiation and commonly, with metastasis, spread of the cancer to other tissues and organs. Cancers are malignant growths. In contrast, benign growths remain encapsulated and grow within a well-defined area. Although benign tumors may be fatal if untreated, due to pressure on essential organs, as in the case of a benign brain tumor, surgery or radiation are the preferred methods of treating growths which have a well defined location. Drug therapy is used when the tumor has spread, or may spread, to all areas of the body.
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.
Anticancer Drug, also called Anti-Neoplastic drug, that is effective in the treatment of malignant, or cancerous, disease. There are several major classes of anticancer drugs; these include Alkylating Agents, Anti-metabolites, Plant Alkaloids and Hormones.
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.
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
Shortened description of STATURAL ACTIVITY RELATIONSHIP OF ANTIMETABOLITES & its MECHANISM OF ACTION - ANTINEOPLASTIC AGENTS (folate antagonist, purine antagonist & pyridine antagonist)(MEDICINAL CHEMISTRY)
quite useful for B PHARMACY & Pharm D Students.
Aminoglycosides(medicinal chemistry by p.ravisankar)Dr. Ravi Sankar
Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
Definition
Anticancer, or antineoplastic, drugs are used to treat malignancies, or cancerous growths. Drug therapy may be used alone, or in combination with other treatments such as surgery or radiation therapy.
Purpose
Anticancer drugs are used to control the growth of cancerous cells. Cancer is commonly defined as the uncontrolled growth of cells, with loss of differentiation and commonly, with metastasis, spread of the cancer to other tissues and organs. Cancers are malignant growths. In contrast, benign growths remain encapsulated and grow within a well-defined area. Although benign tumors may be fatal if untreated, due to pressure on essential organs, as in the case of a benign brain tumor, surgery or radiation are the preferred methods of treating growths which have a well defined location. Drug therapy is used when the tumor has spread, or may spread, to all areas of the body.
Antibiotics
Dactinomycin, Daunorubicin, Doxorubicin, Bleomycin
Examples of antineoplastic antibiotics include doxorubicin, daunorubicin, bleomycin, mitomycin, and dactinomycin, all of which are derived from species of Streptomyces bacteria.
While these drugs may have antibacterial activity, they are generally too dangerous and toxic for that use. Antineoplastic antibiotics are associated with blood cell damage, hair loss.
Dactinomycin, also known as actinomycin D
C62H86N12O16
Lactone rings in the dactinomycin stabilizes the peptide chains in such a conformation which enables the formation of four extra Hydrogen bonds between phosphodiester oxygens and peptide-NH groups.
Amino acid composition contributes to the biological activity of dactinomycin.
Replacing the proline by hydroxylproline can change the minimal inhibitory concentration of the drug.
The different conformation in the peptide can result in the different biological activity of the drug.
If pipecolic acid is attached with the drug then it can only inhibit the growth of gram positive bacteria but not gram negative bacteria
Replacement of both the proline residues with the pipecolic acid reduces the biological activity of the drug and the binding capacity of the drug with DNA
Replacement of both the proline residues with the pipecolic acid reduces the biological activity of the drug and the binding capacity of the drug with DNA
Osteosarcoma
Soft tissue sarcoma
Locoregional solid tumours
Gestational trophoblastic neoplasm
Metastatic testicular tumours
Ewing’s sarcoma
Ovarian cancer
Childhood rhabdomyosarcoma
Wilms’ tumour (Kidney cancer in children's
Daunomycin
C27H29NO10
anthracycline-type antitumor drugs
Substitution at 2nd position decreases the biological activity of drug.
Biological activity can be increased by substitution at 3rd
8th position has direct relationship with the biological activity of drug and thus, substitution at 8th position can increase the biological activity of drug.
Substitution at 1st and 7th position will have negative impact on the biological activity of the drug.
Acute Myelogenous leukemia
Acute lymphoblastic leukemia
Acute promyelocytic leukemia
Acute Myelogenous leukemia
Acute lymphoblastic leukemia
Acute promyelocytic leukemia
Anthracyclic antibiotic cytotoxic drug
C27H29NO11
Doxorubicin firms complexes with DNA by intercalation between base pairs.
The drug then stabilizes DNA-topoisomerase II and thus topoisomerase activity is inhibited
Relegation of the DNA is prevented
Cell death
Uterine sarcoma
Transitional cell bladder cancer
Thyroid cancer
Thyomas
Soft tissue sarcoma
Small cell lung cancer
Ovarian cancer
Neuroblastoma]
Bleomycin chelates metal ions and produces pseudoenzymes.
ii. The pseudoenzymes so formed reacts with Oxygen to produce hydroxide and superoxides free radicals.
iii. Cleaving of DNA by the free radicals
For the complexation and oxygen activation, N terminal is responsible.
Hodgkin’s lymphoma
This document was prepared by Afifa Binta Saifuddin and her group members for the assignment purpose for Department of Pharmacy, East West University, Bangladesh. Uploaded by Tousif Azmain.
Cellular defense against fatal associations between proteins
and DNA
Date:
July 3, 2014
DNA 'replication fork' reconstituted for the first time
Date:
July 9, 2014
Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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.
Follow us on: Pinterest
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
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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
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.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
NVBDCP.pptx Nation vector borne disease control program
2.Antitumor Antibiotics
1. 1
A. Cytotoxic drugs
1. Alkylating agents
2. Platinum coordination complexes
3.Antimetabolites
4.Antibiotics
5. Plants
B. Targeted drugs
1. Tyrosine protein kinase inhibitors
2. EGF receptor inhibitors
3. Angiogenesis inhibitors
4. Biological response modifiers
C. Hormonal drugs
CLASSIFICATION OF ANTICANCER DRUGS
2. Drugs from Natural source
A variety of the anticancer agents available
today are derived from natural sources
Microbial sources (antibiotics) and
Plants
Both the antibiotic and natural product from
plants classes have multiple inhibitory effects
on cell growth; however,
They primarily act to disrupt DNA function
and cell division.
3. Mechanisms by which these agents target DNA is
Intercalation,
Alkylation, and
Strand breakage either directly or as a result of enzyme
inhibition.
Steps in Intercalation
Intercalating drugs contain a planar aromatic or
heteroaromatic ring system which can slip into the double helix
of DNA and distort its structure.
Drug should induce a cavity between base pairs so that
insertion may occur b/n drug and DNA.
The interaction of the intercalator (drug) and the adjacent base
pairs of DNA occurs by the overlap of p-orbitals of the
intercalator and the base pairs.
The p-orbitals of the intercalator/intercalation species are
provided by a combination of aromatic and conjugated systems
that impart the planarity required for intercalation.
4. The side chains of intercalator has a cationic
moiety, which may form ionic bonds with the anionic
phosphate backbone in DNA.
The overall result of these interactions is to cause
a local bend or kink or cut in DNA resulting in a local
shape distortion.
Inhibition of topoisomerase /DNA gyrase
(Topoisomerase enzymes are responsible for the
unwinding and relaxation of DNA so that transcription
may occur)
5. Classification of Antitumor Antibiotics drugs
Many of the antineoplastic antibiotics are produced by
the soil fungus Streptomyces.
Anthracyclines: Doxorubicin, Daunorubicin,
Epirubicin, Mitoxantrone, and Idarubicin.
Actinomycins/Chromomycins: Dactinomycin
and Plicamycin.
Miscellaneous: Mitomycin and Bleomycin.
6. Antracyclines
Doxorubicin (previously called adriamycin)
belongs to a group of naturally occurring antibiotics called
the anthracyclines, and was isolated from Streptomyces
peucetius in 1967.
It is very similar in structure to Daunorubicin—differing
only in one hydroxyl group at C9 acetyl group in
daunorubicin & hydroxy acetyl group in doxorubicin.
O
O
OH
OH
OH
C CH2
O
OH
OO
H
H
OH
H
NH2H
H
CH3
OCH3
ABCD
Doxorubicin
1
2
3
4 5 6 7
8
9
1011
12
O
O
OH
OH
OH
C CH3
O
OO
H
H
OH
H
NH2H
H
CH3
OCH3
ABCD
Daunorubicin
1
2
3
4 5 6 7
8
9
1011
12
7. The second generation anthracyclines
Epirubicin and Idarubicin lacks the methoxy
group at C4 , so it is more polar and has an
altered metabolism which prolongs its half-
life.
O
O
OH
OH
OH
C CH2
O
OH
OO
H
OH
H
H
NH2H
H
CH3
OCH3
ABCD
Epirubicin
O
OH
OH
OH
OH
C CH3
O
OO
H
H
OH
H
NH2H
H
CH3
ABCD
Idarubicin
1
2
3
4 5 6 7
8
9
101112
8. SAR
• The anthraquinone chromophore is an important structural feature of the
anthracyclines.
• the anthraquinone chromophore, consisting quinone and a hydroquinone
moiety on adjacent rings.
• The phenolic hydroxy groups present in this core were found to undergo
ready acylation and alkylation under standard reaction conditions.
• It has been shown that, O-methylation of the C-6 or C-11 phenolic groups
results in analogs with markedly reduced activity,
• whereas C-4 modifications such as demethylation and deoxygenation do
not affect bioactivity.
• The transformation of the C-5 carbonyl to the corresponding imino
functionality resulted in an analog that retained activity and was found to
be significantly less cardiotoxic than the parent compound.
• Ring-A, alicyclic moiety bearing the two-carbon side chain group and
the tertiary hydroxyl group at C-9 and also having a chiral hydroxy group
at C-7, which in turn connected to the aminosugar unit;
• the amino sugar residue, attached to the C-7 hydroxy group through an a-
glycosidic linkage;
11. Mitoxantrone
It is a simplified, synthetic analogue of the
anthracyclines where the tetracyclic ring system has
been ‘pruned’ back to the planar tricyclic system
required for intercalation.
• There is no sugar ring which is responsible for cardio
toxic side effects.
• The pharmacophore
groups are highlighted in
box and which are responsible
For binding with DNA base
Pairs.
Anthrace ring interculate b/n DNA
base pairs.
12. Uses of Anthracyclines
Doxorubicin is used to treat a broad spectrum of solid
tumours, as well as acute leukaemias, lymphomas, and
childhood tumours.
Daunorubicin is indicated for acute leukaemias.
Epirubicin is considered effective against breast cancer.
Idarubicin is used in the treatment of haematological
malignancies and can be given orally.
Both epirubicin and idarubicin are second-generation
anthracyclines with less cardiac toxicity than doxorubicin
or daunorubicin.
Mitoxantrone is used for the treatment of certain
leukaemias and lymphomas, and for advanced breast
cancer.
13. Side effects of Anthracyclines
Causes cardiotoxicity
Interference with ryanodine receptors of the
sarcoplasmic reticulum in the heart muscle cells
Sugar residue is one of the cause for cvs toxicity
Free-radical formation in the heart
Leads to forms of congestive heart failure, often years
after treatment
Counteract with dexrazoxane
Liposomes can be useful as carriers to deliver
doxorubicin to target tumours and this approach
is associated with less cardiac toxicity.
Extravasation injury produce extensive local
necrosis.
14. Extravasation Injury by Doxorubicin
Redness , swelling blisters Tissue necrosis
surgery to remove tissue permanent damage
15. Actinomycins
The Actinomycins are a group of compounds
that are isolated from various species of
Streptomyces,
Phenoxazone chromophore
And has di pentapeptide portion
The 1St drug from this group is Actinomycin D
which is known as Dactinomycin
Other Pilcamycin
16. Actinomycin-D/ Dactinomycin
Phenoxazone chromophore
And has di pentapeptide
portion
The pentapeptides namely L-
threonine, D-valine, L-proline,
sarcosine, and L-methylvaline
form a lactone via the side
chain hydroxyl of L-threonine
and the carboxyl group of L-
methylvaline
An amide linkage is present b/n
the amino group of L-threonine
and carbonyls of 1 and 9 of
Phenoxazone chromophore
17. • The structural feature of dactinomycin important for
its mechanism of cytotoxicity is
• the planar phenoxazone ring, which facilitates
intercalation between DNA base pairs.
• The peptide loops are located within the minor groove
and provide for additional interactions.
• Dactinomycin binds noncovalently to double-stranded
DNA by partial intercalation between adjacent guanine
cytosine bases resulting in inhibition of DNA function.
• Additional hydrophobic interactions and hydrogen
bonds are formed between the peptide loops and the
sugars and base pairs within the minor groove.
18. Mechanism of action of Dactinomycin
Minor GrooveD
D
By an effect on topoisomerase II
that unwinds the DNA helix for
replication
It intercalates, in the minor groove
of DNA, between adjacent guanine-
cytosine pairs thus preventing
transcription.
DNA synthesis may also be inhibited,
and the agent is considered as cell
cycle specific for the G1 and S
phases.
Block DNA Gyrase/ topoisomerase
Uses
is given mainly intravenously to treat
paediatric solid tumours, including
Wilm's tumour and Ewing's tumour
23. Uses of Mitomycin C
Adenocarcinoma of the stomach, colon, or pancreas.
Its use and application in ophthalmology has been increasing
in recent years because of its modulatory effects on wound
healing.
Current applications include
Pterygium surgery,
Glaucoma surgery,
Corneal refractive surgery,
Cicatricial eye disease,
Conjunctival neoplasia and allergic eye disease.