FFP1 - Introduction to Pharmacology
Definition of a Drug
Drugs are substances with beneficial biological activity.
Limitations of Herbal Medicines
Early reliance on plants presents challenges:
Multiple substances in extracts increase toxicity risks.
Unknown quantities of active ingredients.
Drugs from Herbal Medicine
Well-known drugs derived from plants:
Aspirin from willow bark.
Digitalis from foxglove.
Quinine from cinchona tree.
Morphine from poppy.
Microbe-Derived Drugs
Microbes are a rich source of drugs:
Screening supernatants allows testing of many thousands of products.
Penicillin
Derived from fungus, effective against Staphylococcus aureus.
Basis for many antibiotics.
Traditional Use of Animal Tissues as Drugs
Animal tissues have been historically significant:
Bear bile used in traditional Chinese medicine.
Modern Use of Animal Tissues as Drugs
Recent sources include:
Heparin from pigs (anticoagulant).
Hirudin from leeches (anticoagulant).
Eptifibatide from viper venom (anti-platelet).
Modern Drug Development
Conventional pharmacology with small synthetic molecules:
Roots in the 19th century with morphine and cocaine.
Early synthetic drugs include acetylsalicylic acid (aspirin) in 1897.
Current Drug Approaches
Advances in biotechnology broaden therapy options:
Recombinant engineered proteins.
Nucleic acid-based therapeutics (e.g., RNAi).
Gene therapy and cell-based therapies.
Protein Therapies
Insulin was purified in 1922 for diabetes treatment.
Advantages: abundant, effective, easy to isolate.
Disadvantages: risk of infection, need for blood donations, complicated modifications.
Recombinant Protein Therapies
Proteins produced from cloned genes in cell lines to ensure safety:
Examples: Insulin, Erythropoietin, Interferon, Factor VIII and IX.
Monoclonal Antibody Therapies
Method to immortalize antibody-producing cells (can fight cancer)
Advantages of monoclonal antibodies:
Specific targeting of antigens.
Not reliant on animal sources for production.
High yield of uniform antibodies.
Disadvantages: High costs and administration via IV.
Monoclonal antibody naming - ends in ‘mab”
Nucleic Acids as Drugs
Antisense molecules inhibit transcription by targeting mRNA.
Aptamers are nucleic acid sequences that bind specifically to proteins.
Example: PATISARAN
Cell-Based Therapies
Involves genetically modified cells or stem cells to treat diseases:
CAR-T cell therapy utilizes patient's T cells modified to attack tumors.
Stem Cell Therapy:
Potential to differentiate into various cell types, primarily for leukemia treatment.
Definition of a DrugDrugs are substances with beneficial biological activity, excluding dietary factors like vitamins unless used excessively.
Sources of Drugs
Early medicines were primarily herbal, leading to safety challenges like toxicity and unknown active ingredient quantities.
Modern approaches include active ingredient purification and drug development from plants, microbes, and animal tissues.
Examples of Drugs from:
Plants: Aspirin (willow bark), Digitalis (foxglove), Quinine (cinchona), Morphine (poppy).
Microbes: Penicillin (Penicillium notatum), Cyclosporine (Tolypocladium inflatum).
Animals: Heparin (pigs), Hirudin (leeches), Eptifibatide (viper venom).
Modern Drug DevelopmentIncludes target-led (targeting proteins) and chemistry-led (selecting chemicals) discovery. Limitations of small molecules due to biochemical complexity. Advances in biotechnology allow for recombinant proteins and gene therapies.
Therapies
Protein Therapies: Insulin, hormones are produced; safer recombinant methods introduced.
Monoclonal Antibodies: High specificity, not reliant on animal sources, but are expensive.
Nucleic Acids: Antisense therapy targets mRNA; Gene therapy addresses genetic mutations.
Cell-Based Therapies: Includes CAR-T therapy and stem cell therapy.
ConclusionUnderstanding pharmacology encompasses its historical evolution, therapeutic areas, limitations of herbal medicine, and varied drug discovery approaches.