General Principles of Pharmacology

• Pharmacology


  The study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes
• Drug


  Any substance that brings a change in physiologic function through its chemical action
• Drug target is where the drug exerts its effect
• Lock and key model


  A more suitable model for drug targets, which are not static
• What pharmaceutical products pertain to


  • Any article recognized in pharmacopoeias and any official compendium or any supplement to them
  • Any article intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease of man or animals
  • Any article, other than food, intended to affect the structure or any function of the human body or animals
  • Any article intended for use, as a component of articles, specified in clauses (1), (2) and (3), not including devices or their components, parts and accessories
  • Herbal or traditional drugs as defined in Republic Act No. 9502
• Drug product


  A dosage form
• Dangerous drug


  Highly regulated, e.g. Morphine
• Pharmacopoeias


  A collection of drug monographs
• Major Areas of Pharmacology


  • Medical Pharmacology
  • Toxicology
  • Clinical
  • Environmental
• Pharmacokinetics


  The movement of drug into, through, and out of the body, what the body does to the drug
• Pharmacodynamics


  The study of the biochemical, physiologic, and molecular effects of drugs on the body, what the drug does to the body
• Pharmacokinetics


  Happens before and after pharmacodynamics (drug target)
• High concentration or overdose


  Can lead to adverse effects
• Pharmacotherapeutics


  The application of pharmacological information together with the knowledge of the disease for its prevention, mitigation or cure, as well as to alter normal functions
• Goals of Pharmacotherapeutics


  • To prepare individualized therapeutic plans based on the diagnosis
  • To maintain drug therapy costs and provide quality and effective treatment
  • To ensure patient compliance
  • To avoid/reduce medical errors
• Therapeutic response


  The desired effect of the drug
• Adverse event


  An untoward event, may or may not have causality with the drug
• Types of adverse events


  • Adverse drug reaction - due to a certain drug
  • Toxicity - due to the dose of the drug
  • Medication error - wrong use of the drug
• Side effect


  An extension of a drug's mechanism of action, an expected adverse drug reaction
• The main goal of pharmacotherapeutics is to maximize the therapeutic effects of the drug and minimize side effects
• Pharmacokinetics


  The movement of drug into, through, and out of the body, the study of the time course of drug absorption, distribution, metabolism, and excretion, what the body does to the drug
• LADME

  • Liberation
  • Absorption
  • Distribution
  • Metabolism
  • Excretion
• Liberation


  The release of drug from the dosage form, the process of transforming a drug product into a molecular dispersion
• Factors determining liberation


  • Physicochemical properties
  • Formulation
  • Route of administration
• For a drug to be absorbed and distributed, it must be liberated from its formulation, dissolve in aqueous solutions, and cross hydrophobic barriers
• Absorption


  The passage of drug molecules from the site of administration into the systemic circulation
• Most absorption occurs in the intestine due to its high surface area
• Absorption is a challenge, drugs must be transported across biological membranes to reach the bloodstream
• Mechanisms of drug permeation


  • Passive diffusion through aqueous channels in intercellular junctions
  • Passive diffusion through lipid cell membranes
  • Active transport by carriers into or out of cells
  • Binding to cell surface receptors, endocytosis, and expulsion via membrane-limited vesicles
• When a drug is swallowed, the esophagus just allows as a passageway for the drug to enter the stomach
• Esophagus = No absorption
• Stomach = Minimal absorption
• Intestine = Most absorption
• Absorption


  • (some acidic drugs)
  • (both acidic & basic)
  • due to its high surface area
• In order for a drug to be absorbed, it must be transported across one or more biologic membranes to reach the bloodstream
• Mechanisms of drug permeation

  • Drugs may diffuse passively through aqueous channels in the intercellular junctions (e.g. tight junctions)
  • Drugs may diffuse through lipid cell membranes
  • Drugs with the appropriate characteristics may be transported by carriers into or out of cells
  • Very impermeant drugs may also bind to cell surface receptors, be engulfed by the cell membrane (endocytosis), and then released inside the cell or expelled via the membrane-limited vesicles out of the cell into the extracellular space (exocytosis)
• Passive diffusion


  • The major absorption process for most drugs
  • The process by which molecules spontaneously diffuse from a region of higher concentration to a region of lower concentration
  • No external energy is expended; hence, it is passive
  • Drug must be small and lipid-soluble
• Passive Diffusion


  1. Fick's Law of Diffusion

  2. dQ/dt = rate of diffusion

  3. D = diffusion co-efficient

  4. A = surface area of membrane

  5. K = lipid-water partition coefficient of drug in the biologic membrane that controls drug permeation

  6. h = membrane thickness

  7. CGI-Cp = difference between the concentrations of drug in the gastrointestinal tract and in the plasma
• Most drugs are weak organic acids or bases, existing in unionized and ionized forms in an aqueous environment
• Weak Acid


  • pH < pKa = unionized
  • pH > pKa = ionized