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Questions and Answers
Pharmacokinetics refers to what drugs do in the body.
Pharmacokinetics refers to what drugs do in the body.
False
Monoclonal antibodies have applications in drug therapy.
Monoclonal antibodies have applications in drug therapy.
True
Toxicology studies the benefits of drugs.
Toxicology studies the benefits of drugs.
False
The synthesis of aspirin occurred in 1897.
The synthesis of aspirin occurred in 1897.
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Chemistry-led drug discovery is the same as target-led drug discovery.
Chemistry-led drug discovery is the same as target-led drug discovery.
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Digitalis is derived from the plant Foxglove.
Digitalis is derived from the plant Foxglove.
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Eptifibatide is derived from a fungus.
Eptifibatide is derived from a fungus.
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The dosage of herbal medicines is often precisely known.
The dosage of herbal medicines is often precisely known.
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Drugs have one active component while herbal medicines can have more than one.
Drugs have one active component while herbal medicines can have more than one.
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Homeopathy is regulated like conventional drugs.
Homeopathy is regulated like conventional drugs.
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In drug discovery, target-led discovery starts with identifying the chemical with biological activity.
In drug discovery, target-led discovery starts with identifying the chemical with biological activity.
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The mechanism of action for drugs is often unknown.
The mechanism of action for drugs is often unknown.
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Mepyramine interacts with H1 receptors.
Mepyramine interacts with H1 receptors.
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Cimetidine has a dissociation constant of 33 μM.
Cimetidine has a dissociation constant of 33 μM.
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Ranitidine has a dissociation constant of less than 1 μM.
Ranitidine has a dissociation constant of less than 1 μM.
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Small molecule drugs have always been sufficient for all therapeutic interactions.
Small molecule drugs have always been sufficient for all therapeutic interactions.
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Recent advances in biotechnology include cell-based therapies.
Recent advances in biotechnology include cell-based therapies.
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Early 19th century drug development began with the synthesis of aspirin.
Early 19th century drug development began with the synthesis of aspirin.
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Proteins are considered effective drugs due to their abundance and ease of isolation.
Proteins are considered effective drugs due to their abundance and ease of isolation.
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Chemistry is not a barrier in the development of small molecule drugs.
Chemistry is not a barrier in the development of small molecule drugs.
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Aromatic rings are not a feature typically associated with small molecule drugs.
Aromatic rings are not a feature typically associated with small molecule drugs.
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Aptamers are a type of gene therapy.
Aptamers are a type of gene therapy.
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Stem cells can differentiate into an unlimited number of mature tissue-specific cell types.
Stem cells can differentiate into an unlimited number of mature tissue-specific cell types.
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Chimeric antigen receptor (CAR)-T cell therapy uses genetically modified B cells.
Chimeric antigen receptor (CAR)-T cell therapy uses genetically modified B cells.
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Drug-coated stents are used in cardiology to prevent vessel re-occlusion.
Drug-coated stents are used in cardiology to prevent vessel re-occlusion.
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Cell-based therapies do not involve the use of genetically-modified cells.
Cell-based therapies do not involve the use of genetically-modified cells.
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Insulin was first purified and used to treat diabetes in 1922.
Insulin was first purified and used to treat diabetes in 1922.
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Recombinant proteins have a high potential for viral contamination.
Recombinant proteins have a high potential for viral contamination.
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Monoclonal antibodies can only be produced using animal cells.
Monoclonal antibodies can only be produced using animal cells.
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Antivenin is typically created using serum from horses that have been inoculated with snake venom.
Antivenin is typically created using serum from horses that have been inoculated with snake venom.
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Nucleic acids cannot be used as drugs.
Nucleic acids cannot be used as drugs.
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Monoclonal antibody therapies are often inexpensive to produce.
Monoclonal antibody therapies are often inexpensive to produce.
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Chimeric antibodies are designated with the suffix -omab.
Chimeric antibodies are designated with the suffix -omab.
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Patisiran is an FDA-approved antisense molecule therapy for hereditary amyloidosis.
Patisiran is an FDA-approved antisense molecule therapy for hereditary amyloidosis.
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Pharmacodynamics refers to the study of what happens to drugs in the body.
Pharmacodynamics refers to the study of what happens to drugs in the body.
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The chemical structures of morphine and cocaine were determined before the synthesis of aspirin.
The chemical structures of morphine and cocaine were determined before the synthesis of aspirin.
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Cell therapies overlap with pharmacology as a new area of therapeutics.
Cell therapies overlap with pharmacology as a new area of therapeutics.
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Toxicology is defined as the study of positive effects of drugs.
Toxicology is defined as the study of positive effects of drugs.
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A drug is defined as a chemical that affects the body in a specific way when applied to a physiological system.
A drug is defined as a chemical that affects the body in a specific way when applied to a physiological system.
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Histamine antagonists were already clinically used for H2 receptor inhibition by 1948.
Histamine antagonists were already clinically used for H2 receptor inhibition by 1948.
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Sir James Black was involved in the development of H2 receptor antagonists starting in 1964.
Sir James Black was involved in the development of H2 receptor antagonists starting in 1964.
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Burimamide has poor oral absorption with a dissociation constant of 320 μM for H1 receptors.
Burimamide has poor oral absorption with a dissociation constant of 320 μM for H1 receptors.
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Metiamide has a higher dissociation constant for H2 receptors compared to histamine.
Metiamide has a higher dissociation constant for H2 receptors compared to histamine.
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The concept of H2 receptor antagonists was proposed due to gastric acid secretion caused by histamine.
The concept of H2 receptor antagonists was proposed due to gastric acid secretion caused by histamine.
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Drugs have a single active component, whereas herbal medicines can contain multiple active components.
Drugs have a single active component, whereas herbal medicines can contain multiple active components.
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Homeopathy is considered to have a documented biological effect greater than a placebo effect.
Homeopathy is considered to have a documented biological effect greater than a placebo effect.
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Target-led discovery in drug development begins by identifying the drug target of interest.
Target-led discovery in drug development begins by identifying the drug target of interest.
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Mepyramine is an example of a drug that binds to histamine H1 receptors.
Mepyramine is an example of a drug that binds to histamine H1 receptors.
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Penicillin is derived from a plant.
Penicillin is derived from a plant.
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Eptifibatide originates from an animal source.
Eptifibatide originates from an animal source.
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Chemistry-led drug discovery relies primarily on known mechanisms and effects.
Chemistry-led drug discovery relies primarily on known mechanisms and effects.
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The dosage of conventional drugs is strictly regulated and known compared to herbal medicines.
The dosage of conventional drugs is strictly regulated and known compared to herbal medicines.
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Cimetidine has a dissociation constant of 450 μM.
Cimetidine has a dissociation constant of 450 μM.
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Ranitidine exhibits a stronger interaction with targets compared to Cimetidine.
Ranitidine exhibits a stronger interaction with targets compared to Cimetidine.
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Small molecule drugs have always been effective in developing agents for all therapeutic interactions.
Small molecule drugs have always been effective in developing agents for all therapeutic interactions.
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Recent advances in biotechnology have led to the development of nucleic acid-based therapeutics.
Recent advances in biotechnology have led to the development of nucleic acid-based therapeutics.
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Proteins are considered less effective drugs because they are difficult to isolate.
Proteins are considered less effective drugs because they are difficult to isolate.
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Cell-based therapies always use genetically modified cells.
Cell-based therapies always use genetically modified cells.
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Gene therapy approaches are part of conventional pharmacology.
Gene therapy approaches are part of conventional pharmacology.
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Aromatic rings are commonly found in small molecule drugs.
Aromatic rings are commonly found in small molecule drugs.
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Recombinant proteins eliminate the risk of viral contamination completely.
Recombinant proteins eliminate the risk of viral contamination completely.
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Monoclonal antibodies can be produced without using animals.
Monoclonal antibodies can be produced without using animals.
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Antivenin is produced using serum from horses that are unexposed to snake venom.
Antivenin is produced using serum from horses that are unexposed to snake venom.
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The discovery of the monoclonal antibody method was made in 1975 by Köhler and Milstein.
The discovery of the monoclonal antibody method was made in 1975 by Köhler and Milstein.
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The production of monoclonal antibodies is generally inexpensive.
The production of monoclonal antibodies is generally inexpensive.
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Nucleic acids can be utilized as drugs through the use of 'antisense' molecules.
Nucleic acids can be utilized as drugs through the use of 'antisense' molecules.
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The suffix -zumab indicates a fully human monoclonal antibody.
The suffix -zumab indicates a fully human monoclonal antibody.
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Hirudin is a recombinant protein derived from the plant Brassica napus.
Hirudin is a recombinant protein derived from the plant Brassica napus.
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Study Notes
Pharmacology
- The study of drugs and their effects on living organisms
- Encompasses pharmacokinetics, pharmacodynamics, pharmacotherapeutics, pharmacognosy, and toxicology
Drug Discovery
- Chemistry-led discovery: Identifies chemicals with biological activity and modifies structures to create libraries of analogues
- Target-led discovery: Identifies a target of interest and screens chemicals for binding. Design chemicals based on computer modeling of ligand binding.
- Mepyramine: An example of chemistry-led discovery. Its structure was modified to create a library of analogues.
- H1 Receptor: A target of interest involved in the inflammatory response regulated by histamine. Antihistamines like mepyramine inhibit the H1 receptor.
- Cimetidine and Ranitidine: Drugs discovered using target-led methods. They bind to H2 receptors involved in gastric acid secretion.
Drug Development
- Small molecules: Frequently used drugs with limitations including challenges in developing inhibitors for protein-protein interactions.
- Modern Drug Development: Involves novel therapies like recombinant engineered proteins, nucleic acid-based therapeutics, gene therapy approaches, and cell-based therapies.
Protein Therapies
- Advantages: Abundant, effective, and easy to isolate.
- Disadvantages: Require blood donation, infection risk, difficult to modify.
- Recombinant protein therapies: Utilize genetic engineering to produce proteins in cell lines, circumventing the challenges of isolating proteins from natural sources.
- Examples: Insulin, erythropoietin, interferon, factor VIII and IX, growth factors, hirudin.
Monoclonal Antibody Therapies
- Discovery: Developed by Kohler and Milstein in 1975. Antibody-producing cells from the spleen are fused with myeloma cells resulting in hybridoma cells that produce a specific antibody (monoclonal antibody).
- Application: Targeted treatment for various conditions including cancer and autoimmune diseases.
- Benefits: High specificity, targeting single epitope on a single antigen; produced in large quantities with predictable batch properties, and eliminates the need for animal use.
- Limitations: Expensive to produce, typically require intravenous administration.
-
Nomenclature:
- Mouse Moabs -omab (e.g., Tositumomab)
- Chimeric antibodies -ximab (e.g., Infliximab)
- Humanised antibodies -zumab (e.g., Natalizumab, Trastuzumab)
- Human antibodies -umab (e.g., Adalimumab)
Antivenin/Antivenom
- Treatment: Used for snake and spider bites.
- Production: Typically derived from horse serum containing antibodies against venom obtained after the horse is inoculated with snake venom.
- Risks: Can produce allergic reactions because horse serum is foreign.
Nucleic Acid-Based Therapeutics
- Antisense Molecules: A single-stranded DNA or RNA sequence complementary to a specific target mRNA. Can inhibit transcription.
- Example: PATISARAN - an FDA-approved RNAi therapy for hereditary amyloidosis with polyneuropathy.
- Aptamers: Short, single-stranded DNA or RNA sequences with highly specific binding to target molecules (proteins, peptides, and small molecules).
Gene Therapy
- Use: Targeted treatment for diseases caused by genetic mutations or altered gene expression.
- Mechanism: Involves delivering genes to cells to replace a faulty gene or introduce a new gene to combat disease.
Cell-Based Therapies
- Approaches: Use genetically modified cells to treat diseases or apply stem cells to regenerate damaged tissues.
- Stem cell therapies: Utilize embryonic or self-renewing multipotent stem cells, often used to treat leukemia.
- Adoptive cell transfer therapy: "Living drugs" - CAR-T cell therapy. T cells are genetically modified to express synthetic receptors recognizing tumor antigens - enhancing their ability to destroy malignant cells.
Medical Devices
- Regulation: Regulated by different legislation compared to drugs.
- Blurring the lines: Technological advancements have blurred the boundaries between drugs and devices.
- Drug-coated stents: Provide a therapeutic effect by releasing drugs to prevent vessel re-occlusion.
What is Pharmacology?
- The study of drugs and their effects on living organisms
- Includes pharmacokinetics, pharmacodynamics, pharmacotherapeutics, pharmacognosy, and toxicology
- Study of drugs from naturally occurring sources is known as pharmacognosy
- Toxicology focuses on the study of adverse effects of drugs
The Evolution of Pharmacology
- 3400 BC: Egyptians used inhalation of herbs to relieve asthma symptoms
- 1000 BC: Ma huang was ingested to alleviate asthma symptoms
- 1800s: Chemical structures of morphine, cocaine, and aspirin were determined
- 1897: Aspirin was synthesized
Drug Sources
- Plants: Foxglove, digitalis
- Animals: Viper, eptifibatide
- Microbes: Penicillium notatum (fungus), penicillin
Drugs vs. Herbal vs. ‘Alternative’ Medicine
- Drugs: Biologically active, single active component, known dose, regulated manufacture/sale, biological effect > placebo
- Herbal: Biologically active, >1 active component, estimated dose, generally unregulated manufacture/sale, biological effect > placebo
- Homeopathy: No biological activity, no active component (?), dose = 0 (?), unregulated manufacture/sale, placebo effect only
Drug Targets
- Receptors
- Enzymes
- Ion channels
- Transporters
Drug Discovery Approaches
- Chemistry-led discovery: Identify chemical with biological activity, modify chemical structure to make a library of analogues, screen analogues for biological activity, generate structure-activity relationships, mechanism often unknown
- Target-led discovery: Identify drug target of interest, screen chemicals for binding to target, design chemical entities based on computer modelling, mechanism known and effect predicted
An Example of Chemistry-Based Drug Development: Ranitidine
- 1948: Histamine antagonists already clinically used (H1 receptor selective), histamine caused gastric acid secretion, proposal of another histamine receptor (H2), clinical utility for treatment of peptic ulcers (none available at that time)
- 1964: Program established to develop antagonists of H2 receptors, synthesis of histamine analogues testing for H2 selectivity
Mepyramine Binding to H1 Receptors
- Mepyramine is an antihistamine that blocks H1 receptors
- Understanding the molecular mechanism of antihistamines like mepyramine binding to H1 receptors helps in drug development and understanding their effects
Small Molecule Drugs - Problems
- Difficult to develop small molecule agents for all interactions, especially between proteins
- Chemistry can be too complex
Modern Drug Development
- Conventional pharmacology uses small synthetic molecules
- Recent advances in biotechnology have led to new therapies:
- Recombinant engineered proteins
- Nucleic acid-based therapeutics
- Gene therapy approaches
- Cell-based therapies
Protein Therapies
- Proteins have long been used as drugs, initially purified from natural sources
- Advantages of using proteins: Plentiful, effective, and easy to isolate
- Disadvantages of using proteins from natural sources: Require blood donation, infection risk, difficult to modify
- Recombinant proteins: Solve the disadvantages of using proteins from natural sources by cloning the protein-encoding gene into a cell line to produce the desired protein
Recombinant Protein Therapies
- Protein not isolated, but protein-encoding gene cloned into cell line
- Cells generate ‘recombinant’ protein that is expressed and purified
- Limited potential for viral contamination
- Examples: Insulin, Erythropoietin, Interferon, Factor VIII and IX, Growth factors, Hirudin (Brassica napus)
Monoclonal Antibody Therapies
- Köhler and Milstein discovered a method to immortalize antibody-producing cells (1975)
- Antibody-producing cells from the spleen fused with myeloma cells (cancer cells)
- This allows for the production of monoclonal antibodies that target a single epitope on an antigen
Value of Monoclonal Antibody Therapies
- Advantages: Single epitope on a single antigen, large amounts of antibody can be produced, predictable batch properties, no need to use animals in production
- Disadvantages: Expensive to make, have to be given intravenously
Monoclonal Antibody Nomenclature
- Mouse MoAbs: -omab (e.g., Tositumomab)
- Chimeric antibodies: -ximab (e.g., Infliximab)
- Humanized antibodies: -zumab (e.g., Natalizumab, Trastuzumab)
- Human antibodies: -umab (e.g., Adalimumab)
Antivenin/Antivenom
- Used to treat snake and spider bites
- Usually, serum from a horse inoculated with snake venom is used
- Horse serum is foreign and can trigger immune reactions
- Anti-horse antibodies are used to counter these immune reactions
Nucleic Acids as Drugs
- Nucleic acids can be used as drugs in two ways:
- Antisense molecules: Complementary mRNA chain can bind and inhibit transcription
- siRNA (small interfering RNA): siRNA molecules target and degrade specific mRNAs
- Patisiran: FDA-approved RNAi therapy for hereditary amyloidosis with polyneuropathy
New Areas of Therapeutics
- New areas of therapeutics that overlap with pharmacology include:
- Cell therapies
- Gene-based therapies
- Engineered antibodies
- Small molecule inhibitors
- Antibody-drug conjugates
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Description
Explore the fascinating world of pharmacology, focusing on drug discovery processes and their development. This quiz covers the essential concepts around pharmacokinetics, pharmacodynamics, and different drug discovery methods including chemistry-led and target-led approaches. Test your knowledge on significant drugs and their mechanisms of action.
