Organic Medicinals and Pharmacodynamics

Organic Medicinals

• Organic medicinal study of pharmaceutical chemistry focused on the discovery, synthesis, and design of bioactive molecules.

• Pharmacodynamics studies how drugs interact with targets like enzymes, proteins, lipids, and receptors, and nucleic acids.

• Enzymes as drug targets include active site inhibitors.

  • Reversible inhibitors compete with endogenous substrates for active sites.
  • Irreversible inhibitors form covalent bonds, permanently inactivating enzymes.
  • Allosteric site inhibitors bind to sites other than the active site, inducing a conformational change that inactivates the enzyme.
  • Uncompetitive inhibitors bind to the enzyme-substrate complex, preventing the reaction from proceeding.

• Receptors as drug targets are cell components, usually proteins, in cell membranes or cytoplasm.

  • Agonists bind to receptors, activating them similarly to endogenous ligands.
    • Three requirements for agonist binding: correct functional groups, correct orientation, correct site
    • Allosteric modulators bind to sites other than the ligand binding site, indirectly affecting receptor activity. (e.g., benzodiazepines on GABA receptors).
  • Antagonists bind to, yet do not activate receptors, preventing endogenous ligands from binding.
    • Requirements/strategies for antagonist binding: correct functional groups & the correct binding position
    • Other mechanisms: allosteric modulators & umbrella effect
  • Partial agonists activate receptors less than endogenous ligands.
  • Inverse agonists bind to receptors and inhibit their constitutive activity (activity in the absence of an endogenous ligand).
  • Desensitization occurs when receptors become less responsive due to prolonged agonist binding.
  • Sensitization occurs when receptors become more responsive due to prolonged antagonist binding.
  • Tolerance is a situation where increased doses of a drug are required over time to achieve the same effect, often due to receptor desensitization or dependence.
  • Dependence is related to the body's ability to adapt to the presence of a drug. Withdrawal symptoms occur if the drug is stopped due to abnormal levels of target receptor.

• Nucleic acids as drug targets involve intercalating and non-intercalating agents.

  • Intercalating agents slip between DNA base pairs, disrupting replication and transcription.
    • Examples include, Podophyllotoxins, Camptothecin
  • Non-intercalating agents prevent DNA replication or repair.
    • Examples include, Alkylating agents, Nitrogen Mustards, Cyclophosphamide, Cisplatin

• Other components like the journey of the drug in the body, are examined via pharmacokinetics.

Pharmacokinetics

• Absorption: Transfer of drug from administration site to systemic circulation. Factors influencing absorption include ionization, pH, and lipid solubility.
• Distribution: Transfer of drug from blood to cells. Factors involved include plasma protein binding and drug's ability to enter cells.
• Metabolism: Biotransformation of drugs to more polar metabolites.
  • Phase I reactions (e.g., oxidation, hydrolysis): Usually make drugs more polar.
  • Phase II reactions (e.g., glucuronidation, sulfation): Conjugate drugs with endogenous molecules to make them more water-soluble, and usually detoxify them.
• Excretion: Removal of drugs from the body. Common pathways include renal excretion and biliary excretion.

Adrenergic Drugs

• Catecholamines are adrenergic compounds with a catechol ring and alkylamine chain.
  • Biosynthesis, metabolism, and structure-activity relationships (SAR) are essential characteristics.

Cholinergic Drugs

• Acetylcholine (ACh) is the primary neurotransmitter in the peripheral and central nervous systems.
  • Has acetylcholine production, metabolism, and structure-activity relationships (SAR).
• Cholinomimetics and cholinergic antagonists are drugs that affect the acetylcholine system.

Antibacterials

• Antibacterial drugs target various bacterial components, including cell walls and protein synthesis. (Examples include Penicillins, Cephalosporins, Carbapenems, etc)
• General structure-activity relationships (SARs) for various drugs.

Antivirals

• Antiviral drugs are directed at different components of viral replication. (Examples include Acyclovir, Valacyclovir, Desciclovir etc)

Other Anti-cancer Drugs

• Anti-cancer drugs target various cellular processes, including DNA replication and protein synthesis.
• Other, more general, anti-cancer drugs include specific examples, such as methotrexate, 5-fluorouracil, cytarabine, and gemcitabine.

Analgesics

• Analgesics are drugs that relieve pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common class of analgesics.
  • General structure-activity relationships (SAR) for several drugs.

Proton Pump Inhibitors (PPIs)

• PPIs are a class of drugs that target the proton pump in the stomach, reducing acid secretion.

Hypoglycemic Agents

• Hypoglycemic agents are drugs that lower blood sugar levels. Examples include insulin, sulfonylureas, and biguanides.
  • Some related structural characteristics and mechanisms.