Slide 1: Introduction to Chemistry in Everyday Life

  • Chemistry plays a significant role in our daily lives
  • It is involved in various aspects of life, including medicine, food, and environment
  • In this lecture, we will focus on the design of antagonists in medicine

Slide 2: What are Antagonists?

  • Antagonists are substances that inhibit or block the actions of a particular receptor or enzyme in the body
  • They oppose the effects of agonists and prevent them from binding to their target sites
  • Antagonists are commonly used in medical treatments to treat a wide range of conditions

Slide 3: Types of Antagonists

  1. Competitive Antagonists:
    • Compete with agonists for the same binding site
    • Bind reversibly to the receptor
    • Can be overcome by increasing the concentration of agonist
  1. Non-competitive Antagonists:
    • Bind to a different site on the receptor
    • Irreversibly inhibit the receptor’s function
    • Cannot be overcome by increasing the concentration of agonist
  1. Physiological Antagonists:
    • Produce the opposite effect of the agonist through a different pathway
    • Counteract the action of the agonist without directly interacting with the same receptor

Slide 4: Examples of Competitive Antagonists

  • Propranolol:
    • Used to treat hypertension and angina
    • Competes with adrenaline for beta-adrenergic receptors in the heart
  • Atropine:
    • Blocks the action of acetylcholine at muscarinic receptors
    • Used to dilate the pupil during eye examinations

Slide 5: Examples of Non-competitive Antagonists

  • Aspirin:
    • Irreversibly inhibits the enzyme cyclooxygenase (COX)
    • Prevents the formation of prostaglandins and thromboxanes
  • Chlorpromazine:
    • Blocks dopamine receptors in the brain
    • Used to treat schizophrenia and bipolar disorder

Slide 6: Examples of Physiological Antagonists

  • Insulin and Glucagon:
    • Insulin promotes the uptake of glucose by cells
    • Glucagon increases blood glucose levels by promoting glycogen breakdown
  • Epinephrine and Histamine:
    • Epinephrine dilates bronchial smooth muscles
    • Histamine constricts bronchial smooth muscles

Slide 7: Drug Design Process

  1. Identify the Target:
    • Determine the receptor or enzyme associated with the disease or condition
  1. Screening and Lead Selection:
    • Identify potential leads through high-throughput screening or rational drug design
  1. Lead Optimization:
    • Modify the lead compounds to improve their affinity, selectivity, and pharmacokinetic properties

Slide 8: Factors Affecting Drug Design

  • Structure-Activity Relationship (SAR)
  • Lipophilicity and Hydrophilicity
  • Stereochemistry
  • Charge and Polarity
  • Molecular Size and Shape

Slide 9: SAR (Structure-Activity Relationship)

  • The relationship between the chemical structure of a drug and its biological activity
  • Helps in designing new compounds with improved potency and reduced side effects
  • Key factors to consider:
    • Functional groups
    • Binding conformation
    • Hydrogen bonding
    • Lipophilic and hydrophilic interactions

Slide 10: Importance of Drug Design

  • Efficient drug design leads to:
    • Safer and more effective medications
    • Reduced side effects
    • Lower development costs
    • Faster approval process

Slide 11:

  • Drug-Receptor Interactions:
    • Drugs interact with specific receptors in the body to produce their desired effects
    • Receptors can be proteins, enzymes, or nucleic acids
    • Drug-receptor interactions are typically based on intermolecular forces such as hydrogen bonding, electrostatic interactions, and hydrophobic interactions
  • Lock-and-Key Model:
    • The drug (key) fits into the receptor (lock) with complementary shape and functional groups
    • The binding between drug and receptor is specific and selective
  • Examples:
    • Opioid receptors and morphine
    • Nicotinic acetylcholine receptors and nicotine

Slide 12:

  • Drug Discovery and Development Process:
    1. Drug Discovery:
      • Identify the target for drug intervention through research and analysis
      • Investigate target structure, function, and role in disease
    2. Hit Generation:
      • Generate small initial compounds that have potential to interact with the target
      • Utilize combinatorial chemistry, virtual screening, or natural product screening
    3. Lead Optimization:
      • Modify the initial compounds to optimize their potency, selectivity, and pharmaceutic properties
      • Aim to enhance drug-like properties and minimize toxicity

Slide 13:

  • Pharmacophore:
    • The essential features or characteristics of a drug molecule that are responsible for its biological activity
    • A pharmacophore model represents the arrangement of these features in three-dimensional space
    • Used in drug design and virtual screening to identify compounds with similar pharmacophoric properties
  • Pharmacophoric Features:
    • Hydrophobic groups
    • Hydrogen bond acceptors
    • Hydrogen bond donors
    • Positive or negative charge centers
    • Aromatic or conjugated systems

Slide 14:

  • Quantitative Structure-Activity Relationship (QSAR):
    • A mathematical model that relates the structure of a compound to its biological activity or potency
    • Typically uses physicochemical properties as descriptors of the compound
    • Enables prediction of activity for new compounds based on their structural characteristics
  • QSAR Equation:
    • Activity = f(physicochemical properties)
    • Properties may include molecular weight, partition coefficient, electronic properties, and topological indices

Slide 15:

  • Drug Metabolism:
    • The process by which the body converts drugs and other foreign compounds into metabolites that can be eliminated
    • Two main phases:
      1. Phase I metabolism: Functionalization reactions (oxidation, reduction, hydrolysis)
      2. Phase II metabolism: Conjugation reactions (glucuronidation, sulfation, acetylation)
  • Metabolism Considerations in Drug Design:
    • Metabolic stability: Prevent excessive metabolism and maintain therapeutic levels
    • Prodrugs: Use inactive compounds that are converted into active drugs through metabolism
    • Metabolite toxicity: Avoid formation of toxic metabolites

Slide 16:

  • Drug Delivery Systems:
    • Enhance drug stability, bioavailability, and targeting to specific sites in the body
    • Examples:
      • Liposomes: Artificial vesicles for encapsulating drugs
      • Nanoparticles: Small particles used for targeted drug delivery
      • Implants and patches: Provide sustained release of drugs
  • Importance of Drug Delivery Systems:
    • Improve patient compliance
    • Reduce side effects
    • Increase therapeutic efficacy

Slide 17:

  • Drug Formulation:
    • The process of designing and developing dosage forms for drug delivery
    • Considerations:
      • Formulation type (tablets, capsules, injections, creams)
      • Drug physicochemical properties
      • Stability and shelf-life
      • Dosage strength and administration route
  • Examples:
    • Tablet formulation: Excipients, binders, disintegrants, lubricants
    • Liposomal formulation: Lipids, surfactants, cholesterol

Slide 18:

  • Drug-Drug Interactions (DDIs):
    • Occur when two or more drugs interact with each other, affecting their pharmacokinetic or pharmacodynamic properties
    • Types of DDIs:
      • Pharmacokinetic interactions: Alter drug absorption, distribution, metabolism, or excretion
      • Pharmacodynamic interactions: Enhance or reduce the effects of another drug
  • Example: Warfarin and Aspirin
    • Aspirin inhibits platelet aggregation, increasing the risk of bleeding when combined with warfarin, an anticoagulant

Slide 19:

  • Adverse Drug Reactions (ADRs):
    • Undesirable or unintended effects of a drug that occur at therapeutic doses
    • Types of ADRs:
      • Type A: Predictable and dose-dependent (e.g., gastrointestinal upset with aspirin)
      • Type B: Unpredictable and idiosyncratic (e.g., severe allergic reactions)
  • Minimizing ADRs:
    • Proper dosage adjustment
    • Patient monitoring
    • Identifying and avoiding drugs with high ADR risks

Slide 20:

  • Conclusion:
    • Understanding the design of antagonists plays a crucial role in drug development
    • Chemistry is essential in the discovery, optimization, and formulation of drugs
    • Considerations such as drug-receptor interactions, pharmacophores, and drug metabolism are crucial for successful drug design and development
    • Future advancements in drug design will continue to improve the efficacy and safety of medications.

Slide 21:

  • Drug Interactions:
    • Occur when two or more drugs interact with each other, affecting their pharmacokinetic or pharmacodynamic properties
    • Types of Drug Interactions:
      • Pharmacokinetic interactions: Alter drug absorption, distribution, metabolism, or excretion
      • Pharmacodynamic interactions: Enhance or reduce the effects of another drug
  • Example:
    • Digoxin and Verapamil: Verapamil inhibits the P-glycoprotein pump, leading to increased digoxin concentration and potential toxicity

Slide 22:

  • Adverse Drug Reactions (ADRs):
    • Undesirable or unintended effects of a drug that occur at therapeutic doses
    • Types of ADRs:
      • Type A: Predictable and dose-dependent (e.g., gastrointestinal upset with aspirin)
      • Type B: Unpredictable and idiosyncratic (e.g., severe allergic reactions)
  • Minimizing ADRs:
    • Proper dosage adjustment
    • Patient monitoring
    • Identifying and avoiding drugs with high ADR risks

Slide 23:

  • Stereochemistry in Drug Design:
    • The arrangement of atoms in three-dimensional space affects drug activity
    • Enantiomers: Mirror-image isomers that have different biological activity
    • Chiral Drugs: Contain a stereocenter and may exhibit different pharmacological effects based on their stereochemistry
  • Example: Thalidomide
    • R-thalidomide: Sedative effects
    • S-thalidomide: Teratogenic effects

Slide 24:

  • Polymorphism in Drug Design:
    • Polymorphs: Different crystal forms of the same compound
    • Polymorphism affects drug solubility, stability, and bioavailability
    • Careful consideration of polymorphs is necessary during drug development to ensure consistent and reproducible performance
  • Example: Carbamazepine
    • Three known polymorphic forms, each with different dissolution rates and bioavailability
    • Selection of a specific polymorph can affect the drug’s therapeutic effectiveness

Slide 25:

  • Drug Delivery Systems:
    • Enhance drug stability, bioavailability, and targeting to specific sites in the body
    • Examples of Drug Delivery Systems:
      • Liposomes: Artificial vesicles for encapsulating drugs
      • Nanoparticles: Small particles used for targeted drug delivery
      • Implants and patches: Provide sustained release of drugs
  • Importance of Drug Delivery Systems:
    • Improve patient compliance
    • Reduce side effects
    • Increase therapeutic efficacy

Slide 26:

  • Controlled Drug Release Systems:
    • Allow for a predetermined and sustained release of drugs over an extended period
    • Types of Controlled Drug Release Systems:
      • Matrix Systems: Drugs are uniformly dispersed in a polymer matrix
      • Reservoir Systems: Drugs are contained in a reservoir surrounded by a rate-controlling membrane
  • Example: Transdermal Patches
    • Deliver drugs through the skin for systemic effects
    • Provide consistent drug release over an extended period, ensuring therapeutic levels in the body

Slide 27:

  • Drug Targeting and Prodrugs:
    • Prodrugs: Inactive compounds that are converted into active drugs upon administration or by metabolic processes
    • Targeted Drug Delivery: Direct drugs to specific tissues or cells to enhance efficacy and reduce side effects
    • Ligands or antibodies can be attached to drugs for targeted delivery
  • Example: Antibody-Drug Conjugates (ADCs)
    • Combines the specificity of an antibody with the cytotoxicity of a drug
    • Delivers drugs directly to cancer cells, reducing systemic toxicity

Slide 28:

  • Drug Discovery and Development Process:
    1. Drug Discovery:
      • Identify the target for drug intervention through research and analysis
      • Investigate target structure, function, and role in disease
    2. Hit Generation:
      • Generate small initial compounds that have potential to interact with the target
      • Utilize combinatorial chemistry, virtual screening, or natural product screening
    3. Lead Optimization:
      • Modify the initial compounds to optimize their potency, selectivity, and pharmaceutic properties
      • Aim to enhance drug-like properties and minimize toxicity

Slide 29:

  • Drug Formulation:
    • The process of designing and developing dosage forms for drug delivery
    • Considerations in Drug Formulation:
      • Formulation type (tablets, capsules, injections, creams)
      • Drug physicochemical properties
      • Stability and shelf life
      • Dosage strength and administration route
  • Examples:
    • Tablet formulation: Excipients, binders, disintegrants, lubricants
    • Liposomal formulation: Lipids, surfactants, cholesterol

Slide 30:

  • Conclusion:
    • The design of antagonists plays a crucial role in drug development and therapeutic interventions
    • Factors such as drug interactions, adverse drug reactions, stereochemistry, polymorphism, drug delivery systems, and formulation affect the efficacy and safety of medications
    • The advancements in drug design and development aim to provide more effective and targeted treatment options for various diseases and conditions.