pharmacology

• what is pharmacology?

  • study of drugs & their actions on living systems
• what are drugs?

  • natural product, chemical substance/pharmaceutical preparation of known chemical substance
  • intended for administration in order to produce biological effects & diagnose/treat diseases
• pharmacodynamics - how drugs act?

  • non uniform distribution of drug within body
  • drug molecules must exert some chemical influence on one/more constituents of cell
  • drugs bind to particular component of cell to produce effect
• targets for drug action?

  1. receptors
  2. ion channels
  3. enzymes
  4. transporters
• drug specifity?

  • for drug to be useful must act selectively on particular cells/tissues - must show high degree of binding site specifity
  • proteins with which drugs bind also show high degree of ligand specifity
• drug lock & key?

  • drug target (lock) has region with particular 3d shaped binding site within its structure at which an appropriately shaped ligand (key) can interact
• drug receptor interaction?

  • follows simple mass action relationships - only 1 drug molecule occupies each drug target at any one time & binding is reversible
  • less drug receptors & more drugs = stronger effect
• define affinity?

  • tendency for drug to bind to its receptor
• define efficacy?

  • tendency to activate receptor once bound
• define potency?

  • amount of drug needed for given effect
• what are agonists?

  • activate receptors
  • initate changes in cell function & elicit response
• agonist contentration - effect curves?

  • biological effect measures
  • allows comparison of potencies of different drugs
• Emax?

  • maximal response - 100% - efficacy
• EC50?

  • dose needed for 50% max reponse - potency
• relative potency?

  • compares ec50 values of different agonists
  • only relevant when examined under same experimental conditions
  • smaller EC50 - greater potency
• what are antagonists?

  • drug reduces response to another drug
  • binds to receptor - causes no receptor activation
  • needed to inhibit agonist response by 50%
  • measure of antagonist potency
  • smaller IC50 - greater potency
• competitive antagonism?

  • antagonist & agonist compete for same receptor binding site
  • reversible - can be removed as it binds non covalently
  • irrerversible - binds covalently
• non competitive antagonism?

  • antagonist binds to allosteric site on receptor to prevent activation of receptor
  • reversible/irreversible
• what is pharmokinetics?

  • what body does to drug
• 4 stages of drug disposition?

  1. absorption
  2. distribution
  3. metabolism - irrerversible loss from body - elimination
  4. excretion - irrerversible loss from body - elimination
• for drugs to have effect in body?


  • present in right place
  • at right concentration
  • right amount of time
• knowledge of drug PK data tells us?

  • what dose to give & how often
  • how to change dose in certain medical conditions
  • how some drug interactions occur
• 2 types of drug movement?

  1. bulk flow
  2. diffusion
• bulk flow?

  • in bloodstream/lymphatics
  • unaffected by chemical nature of drug
• diffusion?

  • over short distances
  • lipid solubility
  • transporters
  • ionisation state
• cell membrane of fluid mosaic model?

  • separates cell content from outside environment
  • regulate passage of substances into & out of cells
  • involved in cell recognition, cell signalling, cell adhesion
• phospholipid bilayer?

  • lipids
  • proteins
  • carbohydrates
• amphipathic?

  • hydrophobic
  • hydrophillic
• absorption?

  • how drug enters bloodstream from site of administration
  • oral
  • sublingual
  • rectal
  • inhalation
  • injection
  • application to other epithelial surfaces - skin
  • little absorption occurs until drug enters small intestine - passive diffusion
• factors affecting oral absorption from gut?

  1. gastrointestinal motility
  2. gastrointestinal ph
  3. particle size & formulation
  4. physiochemical factors
  5. food
• distribution?

  • how much drug is moved to various tissues/organs
  • once drug enters systemic circulation its distributed into interstitial & intracellular fluids
  • drugs bound to circulating plasma proteins - glycoproteins/ beta globulin
  • unbound is pharmacologically active - diffuse through membranes & binds to drug target
• 4 body fluid compartments?

  1. plasma - extracellular
  2. interstital fluid - extracellular
  3. lymph - extracellular
  4. intracellular - content of all cells in body
• metabolism?

  • how drug is chemically altered by body by enzymes
  • converted into water soluble to increase renal elimination
  • swallowed drug - digestive system - hepatic portal system - liver - rest of body
• what is primary site of metabolism?

  liver
• bioavailability?

  • fraction of administered drug that gains access to systemic circulation
  • if its low - incomplete absorption, enzyme metabolism - larger dose needed to get therapeutic effect
• phase 1 - activation?

  • catabolic - oxidation, reduction, hydrolysis
  • products more chemically reactive
  • introduce reactive group for phase 2
  • metabolites more polar & less pharamceutically active - excreted in urine
  • some conjugates excreted in bile - reactivated in intestine & reabsorbed
• phase 2 - inactivation?

  • anabolic - conjugation
  • attach to ionised group with endogenous substituents - acetlyation, sulphation, amino acid, fatty acid
  • glacuronidation - both drug & endogenous compound metabolism
• excretion?

  • how much drug is removed from body
  • drugs eliminated unchanged ( if orginal is water soluble) or polar metabolite (if original is lipid soluble)