This document provides an overview of medicinal chemistry and the drug development process. It discusses how most medicines contain a single active organic compound, and how medicinal chemists work to design new drug candidates and improve existing lead compounds. The development process involves natural product discovery, computational modeling, synthesis of analogues, and clinical trials to test safety and efficacy before regulatory approval. Key points covered include the high costs of drug development, common sources of lead compounds like plants and microbes, and safety issues that led to modern clinical trial standards.
Introduction to Medicinal Chemistry(2).pptxRoshanAryal6
Unit I provides an 8 hour introduction to medicinal chemistry including the history of medicinal chemistry and drugs from natural and synthetic origins. It discusses drug discovery and design as well as the advantages and disadvantages of natural, synthetic, and semisynthetic drugs. Key events in the history of medicinal chemistry include the isolation of morphine in 1803, the synthesis of aspirin in the late 1800s, the discovery of penicillin in the 1920s, and the development of numerous drugs throughout the 20th century.
The document provides an introduction to the field of pharmacology, including its history and key concepts. It discusses how pharmacology studies the interaction between drugs and living organisms. Ancient cultures used plant- and animal-based remedies, with varying effectiveness. Modern pharmacology has derived many drugs from natural sources and through synthetic processes. Throughout history, some drugs have been mislabeled, dangerous or led to addiction when regulations were lacking.
Role of natural product in drug discoveryRahul B S
This document provides an overview of the role of natural products in new drug development. It discusses how drug development involves choosing a disease, identifying drug targets, selecting bioassays, and finding lead compounds. Many natural products from plants, microorganisms, marine sources, and animals have been used as lead compounds. Examples are discussed like morphine from poppies, quinine from cinchona, and epibatidine from poison frogs. Isolation, purification, and structural determination are required to develop natural product leads into drugs. While natural products were historically important, their use declined but is now increasing again with new technologies.
The document provides an introduction to pharmacology and the history of drugs. It discusses the origins of key terms related to pharmacology and describes three medical uses of drugs. It then summarizes the historical origins and development of drugs from ancient times through the 1800s-early 1900s, including major milestones. The document also discusses issues with mislabeled/dangerous drugs historically and the development of drug laws and regulatory agencies.
The document discusses various topics related to pharmacology including:
1. Pharmacology is defined as the study of drugs and their interactions with living organisms. It includes the history, sources, uses, and effects of drugs.
2. Important figures in the development of pharmacology include Oswald Schmiedeberg, who established experimental physiology, and Friedrich Serturner, who isolated the alkaloid morphine in 1805.
3. Pharmacology can be divided into clinical pharmacology, pharmacy, therapeutics, toxicology, and other branches dealing with specific areas like chemotherapy and pharmacogenetics.
This presentations includes information about definition of pharmacology, history, nature and sources of drugs, different terms used in Pharmacology, Essential Drugs concept, Routes of Drug Administration, and Agonist and Antagonist.
final ppt of pharmaceutical compounds mcnl 1.pptxgyanaraja2002
This document provides an overview of pharmaceutical compounds and their importance. It discusses how chemistry has led to the development of synthetic drugs that can treat diseases. Some key points covered include:
- Pharmaceutical drugs act by binding to proteins in the body and causing physiological changes like cell death in the case of anticancer drugs.
- Drugs are classified as natural or synthetic and can be antibacterial, antiviral, antiseptics, analgesics, or act on the central nervous system.
- Important drug classes discussed include antipyretics, analgesics, antimalarials, and antibiotics. Specific drugs mentioned include aspirin, chloroquine, penicillin, and streptomycin.
Introduction to Medicinal Chemistry(2).pptxRoshanAryal6
Unit I provides an 8 hour introduction to medicinal chemistry including the history of medicinal chemistry and drugs from natural and synthetic origins. It discusses drug discovery and design as well as the advantages and disadvantages of natural, synthetic, and semisynthetic drugs. Key events in the history of medicinal chemistry include the isolation of morphine in 1803, the synthesis of aspirin in the late 1800s, the discovery of penicillin in the 1920s, and the development of numerous drugs throughout the 20th century.
The document provides an introduction to the field of pharmacology, including its history and key concepts. It discusses how pharmacology studies the interaction between drugs and living organisms. Ancient cultures used plant- and animal-based remedies, with varying effectiveness. Modern pharmacology has derived many drugs from natural sources and through synthetic processes. Throughout history, some drugs have been mislabeled, dangerous or led to addiction when regulations were lacking.
Role of natural product in drug discoveryRahul B S
This document provides an overview of the role of natural products in new drug development. It discusses how drug development involves choosing a disease, identifying drug targets, selecting bioassays, and finding lead compounds. Many natural products from plants, microorganisms, marine sources, and animals have been used as lead compounds. Examples are discussed like morphine from poppies, quinine from cinchona, and epibatidine from poison frogs. Isolation, purification, and structural determination are required to develop natural product leads into drugs. While natural products were historically important, their use declined but is now increasing again with new technologies.
The document provides an introduction to pharmacology and the history of drugs. It discusses the origins of key terms related to pharmacology and describes three medical uses of drugs. It then summarizes the historical origins and development of drugs from ancient times through the 1800s-early 1900s, including major milestones. The document also discusses issues with mislabeled/dangerous drugs historically and the development of drug laws and regulatory agencies.
The document discusses various topics related to pharmacology including:
1. Pharmacology is defined as the study of drugs and their interactions with living organisms. It includes the history, sources, uses, and effects of drugs.
2. Important figures in the development of pharmacology include Oswald Schmiedeberg, who established experimental physiology, and Friedrich Serturner, who isolated the alkaloid morphine in 1805.
3. Pharmacology can be divided into clinical pharmacology, pharmacy, therapeutics, toxicology, and other branches dealing with specific areas like chemotherapy and pharmacogenetics.
This presentations includes information about definition of pharmacology, history, nature and sources of drugs, different terms used in Pharmacology, Essential Drugs concept, Routes of Drug Administration, and Agonist and Antagonist.
final ppt of pharmaceutical compounds mcnl 1.pptxgyanaraja2002
This document provides an overview of pharmaceutical compounds and their importance. It discusses how chemistry has led to the development of synthetic drugs that can treat diseases. Some key points covered include:
- Pharmaceutical drugs act by binding to proteins in the body and causing physiological changes like cell death in the case of anticancer drugs.
- Drugs are classified as natural or synthetic and can be antibacterial, antiviral, antiseptics, analgesics, or act on the central nervous system.
- Important drug classes discussed include antipyretics, analgesics, antimalarials, and antibiotics. Specific drugs mentioned include aspirin, chloroquine, penicillin, and streptomycin.
1.1 Pharmacology- An Introduction
The word pharmacology is derived from two Greek words, pharmacon meaning a drug, and logos meaning an opinion or reason. It can be defined as
“The science which deals with the history, source, physical properties, chemical properties, compounding, biochemical effects, physiological effects, mechanism of action, absorption, distribution, biotransformation, excretion, therapeutic and other uses of drugs, is called pharmacology.”
“The study of a substance that interacts with the living system through chemical processes especially by binding to regulatory molecules and activates or inhibits normal body processes”
“The science of substances used to prevent, diagnose and treat disease.”
Drug:
The word drug comes from Drogue meaning a dry herb. A drug can be defined as:
“A substance, material or product used for the purpose of diagnosis, prevention and relief of symptoms or cure of disease.”
WHO defines drug as:
“A substance, material or product used or intended to be used to modify or explore the physiological processes or pathological states for the benefit of the recipient.”
General Features of a Drug:
• Variability in molecular size
• Variability in shape
• Variability in chemical nature
• Variability in lipid/water partition coefficient
• Variability in degree of ionization
• Physical Properties
• Variability in molecular size
Smaller sized molecules are easily absorbed than larger molecules. Normally the molecular weight is between 100-1000 but may be higher or lower. Streptokinase is an example of large molecular weight drug while lithium or nitric oxides are of small molecular weight.
• Variability in shape
Pharmacology Unit - 1General Pharmacology.pptxNikita Gupta
This document provides an introduction to the subject of pharmacology. It defines key terms like pharmacodynamics, pharmacokinetics, pharmacotherapeutics, toxicology, and clinical pharmacology. It discusses the history of pharmacology from ancient civilizations to modern developments. It also covers the scope of pharmacology, nature and sources of drugs, drug classification systems, routes of drug administration, and types of drug receptors like agonists. The document is serving to introduce students to the overall field of pharmacology.
This document provides an overview of pharmacognosy, including its definition, historical development, and modern applications. It discusses how pharmacognosy is the study of crude drugs from natural sources like plants, animals, and minerals. Over time, the field has advanced from early empirical use of natural remedies to the systematic isolation and characterization of active pharmaceutical ingredients using analytical techniques. Pharmacognosy continues to contribute to drug discovery and development through the study of natural products.
Pharmacology is the study of how drugs act on living systems. It has evolved from early use of natural products by ancient civilizations to treat illnesses, to the modern experimental science involving isolation of active drug compounds and understanding their physiological effects. Key events included isolation of morphine and quinine, development of the field of pharmacokinetics to study how the body affects drugs, and pharmacodynamics to study how drugs affect the body. Most drugs produce their effects by binding to specific receptor proteins in cells to trigger signaling pathways that result in physiological responses.
The document provides a history of pharmacology, from ancient times using natural remedies to modern pharmacology as an experimental science. It discusses how drugs were isolated from natural products in the 19th century, including morphine and quinine. Modern pharmacology studies how drugs work on the body through pharmacokinetics, pharmacodynamics and pharmacogenomics. Drugs act by binding to receptors to produce effects through signaling pathways.
The document provides a history of pharmacology, from ancient times using natural remedies to modern pharmacology as an experimental science. It discusses how drugs were isolated from natural products in the 19th century, including morphine and quinine. Modern pharmacology studies how drugs work on the body through pharmacokinetics, pharmacodynamics and pharmacogenomics. Drugs act by binding to receptors to produce effects through signaling pathways.
The document discusses the importance of studying pharmacology, which is the scientific study of drugs and their interaction within biological systems. It defines key terms like pharmacology, pharmacist, drug, and outlines the major branches and concepts of pharmacology such as pharmacokinetics, pharmacodynamics, toxicology, and provides a brief history of the evolution of pharmacology from ancient to modern times.
This document discusses current trends in natural health products and research on natural products from garlic and perilla. It provides background on the history of using natural products for medicine beginning with Hippocrates prescribing garlic. Developments are discussed such as the discovery of antibiotics from microorganisms in the 1970s and shift to laboratory drug discovery in the 1980s. The presentation will cover organic chemistry, biochemistry, pharmacology and synthetic analogs related to natural product research and development. Studies on garlic are summarized showing that consuming garlic may help lower blood glucose, cholesterol, and triglycerides.
Pharmacology is study of the substances which interact with living system by activating or inhibiting normal body processes. It includes physical and chemical properties, biochemical and physiological effects, mechanism of action, therapeutic uses and adverse effects of drugs.
Natural products from living organisms have historically provided many pharmaceuticals and will continue to be an important source of new drug leads. Compounds are classified as primary or secondary metabolites, with secondary metabolites having non-essential functions but often medicinal properties. Traditional medicine systems rely heavily on plants, with over 65% of the global population using herbal remedies. Oceans are also a rich source of novel compounds from marine organisms.
Natural products in pharmaceutical chemistry Nelson giovanny rincon silvaNelson Giovanny Rincon S
The document discusses the history of natural products in medicine, noting that plants have long formed the basis of traditional medicine systems dating back thousands of years in ancient Mesopotamia, Egypt, China, India, and among the Greeks and Romans. It describes how natural products from plants, animals, and microbes have been the source of many modern drugs and continue to offer novel drug leads. The document also provides examples of important natural products that have been used medicinally and taxonomically classifies natural products based on their biosynthetic origins.
This is an introduction to Pharmacology, which is very helpful for nursing students. This presentation tells about classification, sources, pharmacokinetics, and pharmacodynamics of drugs.
The document discusses the various sources of drugs, which include plants, animals, minerals, microorganisms, synthesis, and genetics. Plants remain a major source, with parts like leaves, stems, and roots utilized. Alkaloids, glycosides, oils, resins, gums, and tannins are the major active pharmacological compounds found in plants. Animals provide substances like insulin, antibiotics from microbes, and minerals like iron. Synthetic and semi-synthetic drugs allow for mass production and structural modifications. Genetic engineering also enables large-scale production of drugs like insulin through recombinant DNA techniques. Overall, the document provides an overview of the diverse natural and manufactured sources that the pharmaceutical industry relies upon to discover and produce
This document provides an overview of the textbook "The Pharmacy Technician 4th Edition" by Dr. Bisrat Hailemeskel. It discusses the origins of pharmacy dating back thousands of years, how medicine has evolved over time, and key developments in the 20th century like antibiotics and the establishment of the FDA. It also describes the role of pharmacists today, the education and licensing process, and how computers are now used extensively in pharmacy settings to manage patient profiles, billing, prescribing, and labeling.
This document provides an introduction to the field of pharmacology. It defines pharmacology as the study of substances that interact with living systems, including drugs. It discusses the classification of drugs based on site of action, chemical structure, mechanism of action, and other factors. The document also covers the sources of drugs, including plants, animals, microorganisms, and chemicals. It discusses the nomenclature of drugs, including generic names versus brand names. Finally, it provides a brief history of the field and discusses the scope of modern pharmacology.
Pharmaceuticals, Personal Care Products & Chemicals of Concern v2zq
Pharmaceuticals, Personal Care Products & Chemicals of Concern - Resources for Healthy Children www.scribd.com/doc/254613619 - For more information, Please see Organic Edible Schoolyards & Gardening with Children www.scribd.com/doc/254613963 - Gardening with Volcanic Rock Dust www.scribd.com/doc/254613846 - Double Food Production from your School Garden with Organic Tech www.scribd.com/doc/254613765 - Free School Gardening Art Posters www.scribd.com/doc/254613694 - Increase Food Production with Companion Planting in your School Garden www.scribd.com/doc/254609890 - Healthy Foods Dramatically Improves Student Academic Success www.scribd.com/doc/254613619 - City Chickens for your Organic School Garden www.scribd.com/doc/254613553 - Huerto Ecológico, Tecnologías Sostenibles, Agricultura Organica www.scribd.com/doc/254613494 - Simple Square Foot Gardening for Schools - Teacher Guide www.scribd.com/doc/254613410 - Free Organic Gardening Publications www.scribd.com/doc/254609890 ~dep.state.fl.us
The document provides an overview of the history of pharmacy and healthcare. It discusses how medicine originated from religious and magical beliefs and transitioned to more scientific study. Key developments included Hippocrates' humors theory, natural medicines derived from plants, and major discoveries like penicillin, insulin, and DNA. The 20th century saw major advances in pharmaceutical drugs and their regulation. Today, pharmacy involves dispensing prescriptions in various settings using computer systems, while pharmacists require a PharmD degree and licensing.
Dr zare habibeh plant drug for cancer preventionhzare
This document discusses several plants and plant-derived compounds that have anti-cancer properties. It begins with a brief history of medicinal plants and provides examples of plants like willow bark containing salicylic acid, the precursor to aspirin. It then discusses the use of taxol derived from yew trees and the alkaloids vinblastine and vincristine from Madagascar periwinkle in cancer treatment. Other sections introduce saffron for its anticancer carotenoids crocin and crocetin, and lycopene's potential anti-cancer activity. The document concludes with an overview of molecular mechanisms of action for various chemotherapeutic agents.
1.1 Pharmacology- An Introduction
The word pharmacology is derived from two Greek words, pharmacon meaning a drug, and logos meaning an opinion or reason. It can be defined as
“The science which deals with the history, source, physical properties, chemical properties, compounding, biochemical effects, physiological effects, mechanism of action, absorption, distribution, biotransformation, excretion, therapeutic and other uses of drugs, is called pharmacology.”
“The study of a substance that interacts with the living system through chemical processes especially by binding to regulatory molecules and activates or inhibits normal body processes”
“The science of substances used to prevent, diagnose and treat disease.”
Drug:
The word drug comes from Drogue meaning a dry herb. A drug can be defined as:
“A substance, material or product used for the purpose of diagnosis, prevention and relief of symptoms or cure of disease.”
WHO defines drug as:
“A substance, material or product used or intended to be used to modify or explore the physiological processes or pathological states for the benefit of the recipient.”
General Features of a Drug:
• Variability in molecular size
• Variability in shape
• Variability in chemical nature
• Variability in lipid/water partition coefficient
• Variability in degree of ionization
• Physical Properties
• Variability in molecular size
Smaller sized molecules are easily absorbed than larger molecules. Normally the molecular weight is between 100-1000 but may be higher or lower. Streptokinase is an example of large molecular weight drug while lithium or nitric oxides are of small molecular weight.
• Variability in shape
Pharmacology Unit - 1General Pharmacology.pptxNikita Gupta
This document provides an introduction to the subject of pharmacology. It defines key terms like pharmacodynamics, pharmacokinetics, pharmacotherapeutics, toxicology, and clinical pharmacology. It discusses the history of pharmacology from ancient civilizations to modern developments. It also covers the scope of pharmacology, nature and sources of drugs, drug classification systems, routes of drug administration, and types of drug receptors like agonists. The document is serving to introduce students to the overall field of pharmacology.
This document provides an overview of pharmacognosy, including its definition, historical development, and modern applications. It discusses how pharmacognosy is the study of crude drugs from natural sources like plants, animals, and minerals. Over time, the field has advanced from early empirical use of natural remedies to the systematic isolation and characterization of active pharmaceutical ingredients using analytical techniques. Pharmacognosy continues to contribute to drug discovery and development through the study of natural products.
Pharmacology is the study of how drugs act on living systems. It has evolved from early use of natural products by ancient civilizations to treat illnesses, to the modern experimental science involving isolation of active drug compounds and understanding their physiological effects. Key events included isolation of morphine and quinine, development of the field of pharmacokinetics to study how the body affects drugs, and pharmacodynamics to study how drugs affect the body. Most drugs produce their effects by binding to specific receptor proteins in cells to trigger signaling pathways that result in physiological responses.
The document provides a history of pharmacology, from ancient times using natural remedies to modern pharmacology as an experimental science. It discusses how drugs were isolated from natural products in the 19th century, including morphine and quinine. Modern pharmacology studies how drugs work on the body through pharmacokinetics, pharmacodynamics and pharmacogenomics. Drugs act by binding to receptors to produce effects through signaling pathways.
The document provides a history of pharmacology, from ancient times using natural remedies to modern pharmacology as an experimental science. It discusses how drugs were isolated from natural products in the 19th century, including morphine and quinine. Modern pharmacology studies how drugs work on the body through pharmacokinetics, pharmacodynamics and pharmacogenomics. Drugs act by binding to receptors to produce effects through signaling pathways.
The document discusses the importance of studying pharmacology, which is the scientific study of drugs and their interaction within biological systems. It defines key terms like pharmacology, pharmacist, drug, and outlines the major branches and concepts of pharmacology such as pharmacokinetics, pharmacodynamics, toxicology, and provides a brief history of the evolution of pharmacology from ancient to modern times.
This document discusses current trends in natural health products and research on natural products from garlic and perilla. It provides background on the history of using natural products for medicine beginning with Hippocrates prescribing garlic. Developments are discussed such as the discovery of antibiotics from microorganisms in the 1970s and shift to laboratory drug discovery in the 1980s. The presentation will cover organic chemistry, biochemistry, pharmacology and synthetic analogs related to natural product research and development. Studies on garlic are summarized showing that consuming garlic may help lower blood glucose, cholesterol, and triglycerides.
Pharmacology is study of the substances which interact with living system by activating or inhibiting normal body processes. It includes physical and chemical properties, biochemical and physiological effects, mechanism of action, therapeutic uses and adverse effects of drugs.
Natural products from living organisms have historically provided many pharmaceuticals and will continue to be an important source of new drug leads. Compounds are classified as primary or secondary metabolites, with secondary metabolites having non-essential functions but often medicinal properties. Traditional medicine systems rely heavily on plants, with over 65% of the global population using herbal remedies. Oceans are also a rich source of novel compounds from marine organisms.
Natural products in pharmaceutical chemistry Nelson giovanny rincon silvaNelson Giovanny Rincon S
The document discusses the history of natural products in medicine, noting that plants have long formed the basis of traditional medicine systems dating back thousands of years in ancient Mesopotamia, Egypt, China, India, and among the Greeks and Romans. It describes how natural products from plants, animals, and microbes have been the source of many modern drugs and continue to offer novel drug leads. The document also provides examples of important natural products that have been used medicinally and taxonomically classifies natural products based on their biosynthetic origins.
This is an introduction to Pharmacology, which is very helpful for nursing students. This presentation tells about classification, sources, pharmacokinetics, and pharmacodynamics of drugs.
The document discusses the various sources of drugs, which include plants, animals, minerals, microorganisms, synthesis, and genetics. Plants remain a major source, with parts like leaves, stems, and roots utilized. Alkaloids, glycosides, oils, resins, gums, and tannins are the major active pharmacological compounds found in plants. Animals provide substances like insulin, antibiotics from microbes, and minerals like iron. Synthetic and semi-synthetic drugs allow for mass production and structural modifications. Genetic engineering also enables large-scale production of drugs like insulin through recombinant DNA techniques. Overall, the document provides an overview of the diverse natural and manufactured sources that the pharmaceutical industry relies upon to discover and produce
This document provides an overview of the textbook "The Pharmacy Technician 4th Edition" by Dr. Bisrat Hailemeskel. It discusses the origins of pharmacy dating back thousands of years, how medicine has evolved over time, and key developments in the 20th century like antibiotics and the establishment of the FDA. It also describes the role of pharmacists today, the education and licensing process, and how computers are now used extensively in pharmacy settings to manage patient profiles, billing, prescribing, and labeling.
This document provides an introduction to the field of pharmacology. It defines pharmacology as the study of substances that interact with living systems, including drugs. It discusses the classification of drugs based on site of action, chemical structure, mechanism of action, and other factors. The document also covers the sources of drugs, including plants, animals, microorganisms, and chemicals. It discusses the nomenclature of drugs, including generic names versus brand names. Finally, it provides a brief history of the field and discusses the scope of modern pharmacology.
Pharmaceuticals, Personal Care Products & Chemicals of Concern v2zq
Pharmaceuticals, Personal Care Products & Chemicals of Concern - Resources for Healthy Children www.scribd.com/doc/254613619 - For more information, Please see Organic Edible Schoolyards & Gardening with Children www.scribd.com/doc/254613963 - Gardening with Volcanic Rock Dust www.scribd.com/doc/254613846 - Double Food Production from your School Garden with Organic Tech www.scribd.com/doc/254613765 - Free School Gardening Art Posters www.scribd.com/doc/254613694 - Increase Food Production with Companion Planting in your School Garden www.scribd.com/doc/254609890 - Healthy Foods Dramatically Improves Student Academic Success www.scribd.com/doc/254613619 - City Chickens for your Organic School Garden www.scribd.com/doc/254613553 - Huerto Ecológico, Tecnologías Sostenibles, Agricultura Organica www.scribd.com/doc/254613494 - Simple Square Foot Gardening for Schools - Teacher Guide www.scribd.com/doc/254613410 - Free Organic Gardening Publications www.scribd.com/doc/254609890 ~dep.state.fl.us
The document provides an overview of the history of pharmacy and healthcare. It discusses how medicine originated from religious and magical beliefs and transitioned to more scientific study. Key developments included Hippocrates' humors theory, natural medicines derived from plants, and major discoveries like penicillin, insulin, and DNA. The 20th century saw major advances in pharmaceutical drugs and their regulation. Today, pharmacy involves dispensing prescriptions in various settings using computer systems, while pharmacists require a PharmD degree and licensing.
Dr zare habibeh plant drug for cancer preventionhzare
This document discusses several plants and plant-derived compounds that have anti-cancer properties. It begins with a brief history of medicinal plants and provides examples of plants like willow bark containing salicylic acid, the precursor to aspirin. It then discusses the use of taxol derived from yew trees and the alkaloids vinblastine and vincristine from Madagascar periwinkle in cancer treatment. Other sections introduce saffron for its anticancer carotenoids crocin and crocetin, and lycopene's potential anti-cancer activity. The document concludes with an overview of molecular mechanisms of action for various chemotherapeutic agents.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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2. Medicines
Medicines are amongst the most widely used products on the
planet. The average cost of developing a new candidate drug
is a staggering £515 million. Development costs include not
only the initial research and development, clinical trials and
regulatory affairs but have to account for the high attrition
rate with only 10% of molecules making it to market. Potential
pitfalls include severe side effects, complications with delivery
or simply it may not work as intended. Medicinal chemists
have to keep updating the rules of drug design and develop
tactics to maximise the chances of a molecules success. So
what makes a successful medicine?
3. What do drugs/medication do?
Drugs are substances that alter biochemical proceeses in the
body.
If a drug has beneficial effects it is a medicine.
Medicines usually contain the active ingredient (drug) and
other ingredients.
4. Discovery and Design
The shelves of a typical pharmacy contain about 2000
medications.
Most medicines contain a single active ingredient , usually an
organic compound.
6. Paracetamol
Prostaglandins are substances released in response to illness
or injury. Paracetamol blocks the production of
prostaglandins, making the body less aware of the pain or
injury.
7. Paracetamol
Side effects can include:
• a rash or swelling – this could be a sign of an allergic
reaction
• hypotension (low blood pressure) when given in
hospital by infusion (a continuous drip of medicine into
a vein in your arm)
• liver and kidney damage, when taken at higher-than-
recommended doses (overdose)
8. Discovery and Design
The goal of medicinal chemists is to find compounds that have
potent effects on given diseases with minimum side effects.
A drug must be selective, it must be transported to the
correct cells in the body and must react in the selected cells.
9. Herbs used by humans since ancient times can provide
starting points for medicines.
Discovery and Design
Quinine from the bark of
cinchona tree is used to
treat malaria
Foxglove contains
digitoxin a cardiac
stimulant
10. Herbs used by humans since ancient times can provide
starting points for medicines.
Discovery and Design
Willow bark contains
salicylates used to
treat fever
Opium compounds
from poppies are
used for sever pain
By 1882 more than fifty different herbs where being grown to treat the sick
11. Lead compounds
Chemists still search the world for plants, berries, flora and
fauna that might contain new medicines.
Once they discover and isolate and determine the structure of
a naturally occurring drug it can serve as a prototype in the
design of other biologically active compounds.
12. Lead compound
• The prototype compound is called the lead compound.
• Analogues of the lead compound are synthesised to try and
improve the therapeutic properties or reduce the side effects.
• Changing the functional groups and structure is called
molecular modification.
13. Cocaine
• Cocaine comes from leaves of erythroxlon coca.
• It is an effective local anaesthetic in low level doses but has
damaging effects on the central nervous system, stimulates
heart rate and causes euphoria which is quickly replaced by
depression.
15. Anaesthetics based on cocaine
100’s of esters have been synthesised, changing chain lengths,
adding substituent's to the ring and changing the alkyl groups
attached to the nitrogen.
Benzocaine Procaine Lidocaine (one of the
most widely used
anaesthetics)
16. Opioids
morphine
Opioids are among the world's oldest known drugs; the therapeutic
use of the opium poppy predates recorded history.
Morphine was first isolated in 1804 by
Friedrich Sertürner, Merck began
marketing it commercially in 1827. At the
time, Merck was a single small chemists'
shop.
Morphine is still the best analgesic; pain
relieving compound and is the standard
used to measure other painkilling agents.
Side effects include addiction,
constipation and no longer responding to
the same dose (drug tolerance).
17. Opioids
codeine
Codeine was first isolated decades
later in 1832 by Pierre Robiquet. It
is used to relive painful coughs and
mild pain.
Nowadays codeine is made from
morphine.
Codeine shows 1/10 of the
analgesic properties of morphine.
18. Opioids
Heroin
Diacetylmorphine
Heroin (diacetylmorphine) was first synthesized in
1874 by English researcher, C.R. Wright.
In 1895 Heinrich Dreser working for The Bayer
Company of Germany, found that diluting morphine
with ethanoic anhydride produced a new drug
without the common morphine side effects which
he later confirmed to be heroin.
Forming the ester derivatives of the two hydroxyl
groups of morphine produces a less polar molecule
so it crosses the blood brain barrier more rapidly
resulting in a quicker high. It is banned because it is
widely abused.
Ethanoic acid impurities are often present in illegally
produced heroin, drug dogs are trained to recognise
the odour of ethanoic acid .
19. Opioids
Etrophine
Understanding how morphine binds to the opiate receptor resulted
in a chemist designing etrophine. Etrophine is 2000 times more
potent than morphine but unsafe for use in humans.
20. Marine chemistry
Marine chemistry is a promising source of drugs for the future.
The study of corals has shown that they contain a large cocktail
of chemicals, many of which have only recently been discovered.
Several look interesting as potential anticancer agents.
21. Marine chemistry
Bengamide A comes from orange sponges, it has unique anti
tumour properties and a range of analogues are being
developed.
Bengamide A
contains six chiral
centres
Bengamide A marine sponge
22. Rainforests
Rainforests contain a bewildering variety of plant and insect life,
often within very small areas. As such they provide a rich source of
plant species. Each of these plant species could have a chemical
locked up within its cells that could become the drug to combat
cancer or AIDS. It is therefore a concern that many plant species
have been lost and will continue to be lost due to deforestation.
23. Venoms
Snake venoms have provided lead compounds for the
development of new drugs. It may seem strange to think of
poisonous chemicals being used in medicine. However, all
drugs are poisons if they are given in too high a dose. For
example, morphine will kill patients in high doses by stopping
breathing. Many of the poisons that are found in nature can
have a useful effect if they are given in much lower non-toxic
doses.
24. Microbes
Microorganisms such as bacteria and fungi have provided a rich
source of antibacterial drugs, especially since the Second World
War. Bacteria and fungi produce antibacterial agents because
microorganisms are continually competing against each other to
colonise and survive. A microorganism that can produce a poison
to kill off its competitors is obviously at an advantage and is
more likely to flourish.
25. Biochemistry
Our own bodies give us clues for new drugs. By understanding
how the body works at the molecular level, we can design new
drugs based on the mechanism of action of hormones and other
chemical messengers within the body.
Medicinal chemists therefore need to cooperate closely with
pharmacologists, geneticists, biochemists and microbiologists.
26. Serendipity in drug development
Workers using nitroglycerin in explosives factories experienced
severe headaches. It was discovered it dilates blood vessels in
the brain and is now used to relieve the symptoms of angina.
Viagra was synthesised by Pfizer's, it was screened as a
treatment for angina and hypertension. During phase 1 trials, it
was discovered it had the ability to treat erectile dysfunction.
Nitroglycerin Viagra (silenafil)
27. Computational chemistry
Modern analytical techniques coupled with computer-aided
molecular modelling have enabled biochemists to work out the
precise structure of some enzymes and receptor sites.
28. Computational chemistry
Computer-generated models of possible active compounds can
then be matched with the enzyme or active site. From this, a list
of target molecules can be drawn up and chemists can devise
methods to synthesise these molecules in the laboratory so that
they can be tested for pharmacological activity.
29. Combinatorial chemistry
Research chemists around the world are continually making new
compounds and it is common for pharmaceutical companies to
put these chemicals through a biological screening process to see
if any of them have pharmacological activity. In recent years, a
science called combinatorial chemistry has been developed. This
is a bit like sticking lego blocks together at random.
32. In 1937, US company S E Massengill mixed diethylene glycol, with
sulfanilamide to make a drug in syrup form with a sweet taste.
The sweet preparation had a sour aftertaste – more than 100
people, mostly children, died after taking it. Diethylene glycol is
toxic.
Elixir sulfanilamide disaster of 1937
33. Thalidomide
• 1953 Thalidomide was synthesised by Chimie Grünenthal
• 1955 Distributed as an epilepsy drug
• 1957 Launched as morning sickness treatment
• 1961 Australian William McBride linked hundreds of case of
malformations to thalidomide
35. How do we know drugs are safe
The thalidomide produced is racemic, two enantiomers existed,
one enantiomer was responsible for the health benefits. The
other inhibited an enzyme important to the growth of limbs.
racemic
36. • Drug testing is overseen by the Medicines and Healthcare
Products Regulatory Agency (MHRA)
• Pre-clinical testing
In vitro and in vivo testing to determine if the drug is safe
enough for human testing.
How do we know drugs are safe
37. • Clinical trial exceptions (CTX) applications
File CTX with appropriate authorities before clinical testing
can begin.
• Phase 1 clinical trial
Initial human testing in a small group of healthy volunteers
(six patients given doses lower than proved safe in animals).
How do we know drugs are safe
38. • Phase 2 clinical trial
Test in a small group of patients (designed to test if safe in
patients with the disease and does it have health benefits).
• Phase 3 clinical trial
Test in a large group of patients to show safety and efficacy
(5000 patients).
How do we know drugs are safe
39. • Marketing authorisation application
Apply to MHRA for approval.
• Manufacturing
Begin full-scale production.
• On-going studies and Phase 4 trials
Continuing monitoring and checking of the drug in use.
How do we know drugs are safe
40. Animal tests
• Use of animals in safety testing is a key stage in drug
development.
• Crucially, animal tests lessen the risk to human volunteers
• Although there are alternatives that can substitute for some
aspects of safety testing, nothing can yet model the
complexity of a living organism.
43. How drugs work
• Biochemical receptors are large protein molecules that can be
activated by the binding of a molecule or drug.
• Receptors are usually protein molecules on the surface of
cells, or enzymes that catalyse chemical reactions (catalytic
receptors).
• The protein receptor has a hollow or cleft called the binding
site into which the messenger molecule can fit and bind.
44. Protein Cell receptors
cell
active
molecule
When the
active
molecule
binds to the
surface it
triggers a
BIOLOGICAL
RESPONCE
Muscle cell
contracts
Nerve cell
sends an
impulse
Stomach
cell
excretes
acid
Cell receptor
Protein
molecule with
binding site
Many different types of cells in the body
have protein molecules on the surface that
act as receptors
The active molecule
leaves the site
unchanged
45. Enzymes as receptors (catalytic
receptors)
Enzyme
Substrate
doesn't fit
Active molecule binds to the enzyme receptor site
causing the enzymes active site to change allowing
the substrate to fit and the reaction to take place
products
Receptors can also be associated with
enzymes. When the active molecule binds
to the receptor it results in the enzyme
changing shape.
Enzyme
receptor
(binding site)
Active site
48. Enzyme inhibitors
‘Smart drugs’, which are designed to improve memory in
Alzheimer’s disease, inhibit an enzyme that degrades
acetylcholine – an important neurotransmitter. Since the
neurotransmitter is not degraded it has a longer lifetime,
resulting in enhanced nerve transmission and better memory.
49. Enzyme inhibitors
Penicillin is another example of a drug that inhibits an enzyme
– in this case a bacterial enzyme involved in the synthesis of
the bacterial cell wall. The bacteria can no longer synthesise
its cell wall and dies.
50. How do drugs work
Other drug targets include DNA and RNA.
Cis-platinum is a chemotherapeutic drug. It binds to DNA
preventing DNA replication and transcription processes.
51. Receptor drug interactions
Binding occurs as a result of noncovalent interactions
between the receptor and the drug molecules.
Knowing about the molecular interactions of drugs and
receptors allows chemists to design compounds that might
have desired biological activities
52. Receptor Shape and binding
Drug
molecule
Receptor protein binding
site
The overall shape and size of the drug has to be
such that it fits the binding site
53. Shape and binding
Drug
molecule
Receptor protein binding
site
The functional groups on both the drugs and
receptors are positioned such that the drugs can
interact and bind to the receptor
54. Van der Waal’s interactions
Receptors and drug molecules can form van der Waal’s
interaction when brought close together e.g. London’s forces
between hydrophobic regions or dipole-diploe interactions.
Hydrophobic pocket Dipole-dipole interactions
55. A group that provides a hydrogen to a hydrogen bond is said
to be acting as a hydrogen bond donor.
H-bond donor: look for an H atom connected to an N or O
atom.
Hydrogen bonding interactions
56. A group that provides an oxygen or nitrogen lone pair or
fluorine is said to be acting as a hydrogen bond acceptor.
H bond acceptor: look for an N O or F with at least one lone pair
of electrons.
Hydrogen bonding interactions
60. Lidocaine
• Lidocaine is a local anaesthetic (sodium channel blocker)
hydrophobic
hydrophobic
H bond acceptor
H bond acceptor
H bond acceptor or dipole –diploe interaction
hydrophobic
H bond donor
H bond donor or ionic
interaction
61. Classification of drugs
After attachment to a receptor site, a drug may either initiate
a response or prevent a response from occurring.
62. Agonist
An agonist is a drug which produces a response similar to the
body’s natural response.
Agonists interact by binding to the receptor site and
competing with the natural compound
63. Antagonist
An antagonist drug interacts with the receptor site and
produces no response but prevents the action of the body’s
natural active compound.
64. Structures of drugs
The structural fragment of a drug molecule which confers
pharmacological activity upon it normally consists of different
functional groups correctly orientated with respect to each
other.
The overall shape and size of the drug has to be such that it fits a
binding site. The functional groups on both the drugs and the
receptor are positioned such that the drugs can interact with and
bind to the receptor.
By comparing the structures of drugs that have similar effects on
the body, the structural fragment that is involved in the drug
action can be identified.
65. Penicillins
Penicillins are well tried families of drugs that bind to proteins
in the cell walls of bacteria and inhibit bacteria cell wall
synthesis, they are antagonists. New forms of penicillin with
different structures are constantly being developed.
Comparing the active molecules allows chemists to identify
the structural fragment responsible for the drugs activity.
68. Adrenoreceptors
Noradrenaline is produced naturally by the adrenaline gland
in times of stress. It activates sites called adrenoreceptors that
cause changes in the body including increased blood pressure.
Phenylephrine also works directly on the receptors as an
agonist.
Amphetamines work indirectly by causing nerve terminals in
the body to produce noradrenaline.
71. Opioids
codeine
Heroin
Diacetylmorphine
morphine
Overlapping the structures allows the structural fragment that
confers pharmacological activity to be identified.
Once the structural fragment has
been identified, chemists can design
and synthesise potential medicines
with a greater likelihood of success.
72. Receptor - enkephalins
Nerve cells release enkephalins which bind to surface receptors
opening ion channels preventing the nerve cells from firing and
sending pain signals. Enzymes then remove the enkephalins from
the receptor.
Nerve cell
Receptor site
Cell
membrane
K+ K+
K+ Ion channel closed
73. Cell
membrane
Opiates - receptor
Morphine and other opiates bind to the receptor but the
enzymes cannot remove them as a result relieving pain
symptoms.
Receptor site
Flat hole binds
the aromatic
ring
Cavity binds
carbon chain/
ring
Anion site
binds
nitrogen
K+
K+
Nerve cell
cannot fire
K+ Ion channel
74. Bliss receptor sites
Chemists began to look for other receptor sites. In 1988, specific
receptors were discovered for THC (tetrahydrocannibol, the
active ingredient in marijuana).
The natural key to this receptor was found to be a molecule
called anandamide.
75. Anandamide
Anandamide has been nick named the bliss molecule.
It is produced in areas of the brain associated with memory
movement and thought, suggesting its role is more than just
pleasure.
76. Anandamide and memory
Animal studies suggest that anandamide induces
forgetfulness. Substances that keep anandamide from binding
to its receptor might be used to treat memory loss.
77. Anandamide and chocolate
Chocolate contains three molecules that resemble
anandamide and these molecules may act as agonists.
Another molecule in chocolate is thought to prevent the
breakdown of anandamide.
It is speculated this may be why chocolate gives pleasure.
79. Case studies
The following case studies give examples of how drugs work.
They are included as examples to aid understanding you do not
need to learn them as part of the course.
80. Case study 1 - Asthma
Asthma is a common long-term condition that can cause
coughing, wheezing, chest tightness and breathlessness.
Asthma is caused by inflammation of the small tubes,
called bronchi, which carry air in and out of the lungs.
81. Case study 1 -Asthma
When an asthma sufferer comes
into contact with something that
irritates their lungs – known as a
trigger – their airways become
narrow, the muscles around them
tighten and there is an increase in
the production of sticky mucus
(phlegm).
Common asthma triggers include:
house dust mites
animal fur
pollen
cigarette smoke
exercise
viral infections
82. Case study 1 - Asthma
adrenaline
Bronchodilators, make breathing easier by relaxing the muscles
in the lungs and widening the airways (bronchi).
Adrenaline is a natural bronchodilator produced at nerve
endings to stimulate muscle activity.
Adrenaline however also increases heart rate and blood
pressure, making it unsuitable for treating an asthma attack.
83. Case study 1 - Asthma
Adrenaline was found to bind to three different receptors
producing different effects.
Receptor Effect Outcome
α-receptors
β1-receptors
β2-receptors
Increased blood pressure
Increased heart rate and force
Dilation of bronchi
Unhelpful
Unhelpful
Helpful
84. Case study 1 - Asthma
To over come the side effects an agonist is needed that is
selective for the β2-receptor and activating only the dilation
of the bronchi.
Starting from adrenaline chemists altered the structure to
select β2 activity and produce a longer lasting activity.
adrenaline
85. Case study 1 Asthma - Isoprenaline
The bulky group attached to the nitrogen improved β2 selectivity
86. Case study 1 - Asthma - salbutamol
salbutamol
Salbutamol is found to have even better β2 selectivity since the group
attached to the nitrogen atom is even bulkier. It also produces longer
lasting effects than isoprenaline because of the replacement of the 3-
hydroxyl group on the benzene ring by a hydroxymethyl group. This
modification slows down the metabolism of the drug in the body.
Salbutamol is effective in providing immediate relief from the symptoms of
an asthma attack and also acts very quickly when administered as an
aerosol spray in a specially designed inhaler.
87. Case study 1 - Asthma – bronchial
dilators
salbutamol
salmterol
isoprenaline
Further developments have produced other
medicines that, although slower acting, produce
longer lasting effects, allowing them to be used
as a preventative measure.
All these bronchial
dilators are agonists
88. Case study 2 - Heart attacks Angina
and hypertension
Blood pressure is increased naturally by exercise, stress and
excitement.
Permanently high blood pressure (hypertension) can result in
strokes or heart attacks.
Angina results in sharp chest pain during physical exercise or
stress and is a result of poor blood flow through the coronary
artery and heart.
89. Case study 2 - Heart attacks angina
and hypertension
To lower blood pressure a drug is needed to block the
β1-receptors.
Receptor Effect Outcome
α-receptors
β1-receptors
β2-receptors
Increased blood pressure
Increased heart rate and force
Dilation of bronchi
Unhelpful
Unhelpful
Helpful
90. Case study 2 - β blockers
Pronethalol is antagonist binding to the β1-receptors in the
heart preventing adrenaline from raising blood pressure and
dilating the blood vessels in the heart.
pronethalol
91. When excess histamine is produced in the body it causes the
symptoms of the common cold and allergic responses i.e. Hay
fever.
Drugs which bind to the histamine receptor but do not produce
the same response are known as antihistamines, the bulky
groups in these molecules also prevent the histamine molecule
approaching the receptor.
Antihistamines are antagonist
Case Study 3 - Hay Fever
histamine
meyramine chlorphenamine
ranitidine
92. Case study 4 - Antibiotics
In 1935 Gerland Domagk was a researcher at a German dye
company, that manufactured a red dye called prontosil. His
daughter was dying of streptococcal infection from a cut to
her finger. It was known prontosil had antibacterial
properties when given to animals (in vivo). He gave prontosil
to his daughter and she was cured.
Prontosil
93. Case study 4 - Antibiotics
However when used in vitro (in glass) prontosil did not kill
bacteria. Studies showed bacteria broke down prontosil into
sulfanilimide.
Prontosil
Sulfanilimide
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