Pharmacology

• Pharmacology


  The study of drugs: structure, physical properties, chemical characteristics relevant to its activity as therapeutic agent
• Pharmacology


  The science of substances used to prevent, diagnose and treat diseases
• Drug


  Substance that brings about change in biologic function through its chemical actions
• Drug


  Any article used in the Mitigation, Diagnosis, Prevention and Cure of diseases in man and animals
• Drug


  Defined as "to bind" specific portion of the body
• Drug-receptor interaction will not produce an immediate effect, it must first stimulate the production of an effector

  
• Effectors


  Translates drug-receptor interaction
• Pharmacokinetics


  Action of the body (Katawan) on the Drug (Absorption, Distribution, Metabolism, Elimination)
• Pharmacokinetics


  Fate of the drug inside the body (What will happen to drug)
• Liberation


  Release of drug from its dosage form for it to be absorbed by the body
• Factors affecting liberation


  • Formulation of salts for easy absorption
  • Formulation of prodrug
• Prodrug


  Drugs that are inactive in the native form but active in vivo
• Prodrug


  Drugs that are inactive in vitro/outside the body, but once taken or administered, they become active
• Why we produce prodrugs

  • To enhance absorption
  • To facilitate the drug reaching the target site
  • To alter solubility
  • Formulation of dosage form
• Prodrugs


  • Enalapril (Ethyl ester of enalaprilat)
  • Olsalazine (Dimer of mesalamine)
  • Chloramphenicol palmitate

  
• Absorption


  When the drug enters the systemic circulation (from the site of administration to the systemic circulation)
• Factors affecting absorption


  • Chemical structure (NP > Polar)
  • Variation in particle size & surface area (↓PS and ↑SA)
  • Nature of crystalline form (amorphous — faster, crystalline — slower absorption)
  • Type of tablet coating and matrix
• Distribution


  Drug reaches the target site of action (from systemic circulation to the target site of action)
• Factors affecting distribution


  • Blood flow (↑ in heart, lungs and liver)
  • Capillary permeability (↑ in liver, ↓ in BBB)
  • Protein binding
  • Affinity of drugs to tissue deposits (↑NP)
• Protein binding


  • Warfarin (90% bound to albumin) and phenylbutazone (98% bound to albumin)

  
• Metabolism


  2 types: Phase 1 (functionalization or asynthetic) and Phase 2 (conjugation or synthetic)
• Phase 1 metabolism


  Introduces a polar functional group (-OH, -COOH, -SH, -NH2) to the xenobiotic molecule
• Phase 2 metabolism


  Attach a small, polar, ionizable endogenous compound to the functional handles of Phase 1
• Most drugs under phase 2 metabolism will undergo Glucuronidation Reaction, except for infants or neonates who will undergo sulfation metabolism since they are still not yet well developed

  
• Excretion


  Final loss of drugs from the body
• Elimination


  Metabolism + excretion
• Types of Elimination Kinetics

  • Zero-order Kinetics
  • First-order Kinetics
• Zero-order Kinetics


  Constant amount of drug is eliminated per unit time, elimination is not dependent on its plasma concentration
• First-order Kinetics


  Constant amount in half (50%) eliminated per unit time, dependent on plasma concentration
• Pharmacodynamics


  Action of the Drug on the Body (Katawan), Effect of the drug on the body
• Drug-receptor interaction


  • Affinity: ability of a Ligand to bind to receptors
  • Intrinsic Activity: ability of the ligand to stimulate the receptors; the ability to exert effect
• Agonist


  Binds to regulatory receptors and mimics regulatory effects of the endogenous signaling compounds
• Types of Agonists


  • Full Agonist
  • Partial Agonist
  • Inverse Agonist

  
• Full Agonist


  Maximal effect (100%)

  
• Partial Agonist


  More than zero but less than one intrinsic activity, cannot produce maximal effect

  
• Inverse Agonist


  Zero or less than one intrinsic activity, produce opposite effect

  
• Antagonist


  Drugs that block or reduce the effects of an Agonist; possess 100% affinity but zero intrinsic activity

  
• Classification of Antagonists


  • Functional Antagonism (Physiologic Antagonism)
  • Receptor Antagonism (Pharmacologic Antagonism)
  • Chemical Antagonism (Inactivation)
• Physiological Antagonism


  Binds to different receptors and produce opposite effect
• Physiological Antagonism


  • Caffeine and alcohol
  • Insulin and glucagon