BIOMED SCIE Lecture 5 Basics of Pharmacology II

• Pharmacodynamics


  How drugs produce change in patients (i.e. what the drug does to the body), and the differences in patient responses to medications
• Pharmacodynamics


  • Helps to predict if drug will produce change
  • Will ensure that drug will provide safe, effective treatment

  
• Frequency distribution curve


  • Graphical representation of patients giving a measurable response to different doses of the same drug
  • Peak of curve indicates largest number of patients responding to a particular dose of the drug
  • Does not give an idea of the magnitude of patient response

  
• Frequency response curves


  Used to explain how patients respond differently to medications
• Median effective dose (ED50)


  • The dose required to produce a specific therapeutic response in 50% of a group of patients
  • Middle of the frequency-distribution curve
  • Is the "average/standard" dose – but many require more or less

  
• Median lethal dose (LD50)


  • Often determined in preclinical trials, the dose of drug that will be lethal in 50% of a group of subjects
  • Shown on frequency-distribution curves
  • Used to assess safety of a drug and is necessary for calculating the Therapeutic Index

  
• Median toxicity dose (TD50)


  • Dose that will produce a given toxicity in 50% of a group of patients
  • More practical value in a clinical setting

  
• Therapeutic Index


  • Measure of a drug's safety margin
  • The higher the value, the safer the drug
• LD50 and ED50 are population parameters (not individual)
• the drug to be given to the patient has a “narrow therapeutic index.” What does this mean?

  The drug has a narrow safety margin and even a small increase in dose may produce adverse or toxic effects

  
• Graded dose-response relationship


  • Describes how the therapeutic response to a drug changes as the medication dose is increased
  • Obtained by observing and measuring and graphically representing a single patient's response to different doses of a drug

  
• Graded dose-response curve


  • Phase 1: occurs at lowest dose - Few target cells affected by drug
  • Phase 2: linear relationship - between amount of drug administered and degree of patient response - Most desirable range
  • Phase 3: plateau reached - Increasing dose has no therapeutic effect - Increased dose may produce adverse effects

  
• Efficacy


  • The ability of a drug to produce the desired therapeutic effect
  • Efficacy is the magnitude of the maximal response that can be produced from a particular drug

  
• Potency


  • The relationship between the dose of a drug and the therapeutic effect
  • It refers to the drug's strength
  • A drug is considered more potent when it achieves the intended therapeutic effect at a lower dose, compared with another drug in the same class

  
• Efficacy is almost always more important than potency
• A medication must have demonstrated efficacy to gain approval from the U.S. Food and Drug Administration (FDA) or EMA
• Potency is significant with regards to side effects. Smaller, less potent, doses of medications tend to cause fewer undesirable effects while achieving the intended therapeutic effect

  
• It is commonly misconceived that more potent drugs are more effective because it takes less of a drug to achieve an effect … but this does not mean that the drug is more effective
• Agonist


  A drug that is capable of binding with receptors to induce a cellular response

  
• Partial agonist


  Medication that produces a weaker, or less efficacious, response at a receptor than a full agonist
• Antagonist


  A drug that binds to and occupies a receptor site and blocks/prevents endogenous chemicals/agonists from acting

  
• Receptor


  A cellular macromolecule (usually a protein) to which a drug binds in a dose-dependent manner, to produce a response

  
• Receptor subtypes still being discovered - Permit "fine-tuning" of pharmacology - Two basic receptor types: Alpha and Beta

  
• Agonist drug


  • Salbutamol that mimics adrenaline and binds to beta receptors in the bronchioles and produces the same effect as adrenaline – bronchodilation (Ventolin)
• Antagonist drug


  • Propranolol that binds to beta receptors in the heart. However, it blocks rather than stimulates the beta receptors and prevents adrenaline binding to its receptors. Commonly known as a beta -blocker
• Nonspecific cellular responses


  Caused by drugs that act independently of receptors, such as changing the permeability of cellular membranes like general anaesthetics
• Pharmacogenetics


  • Area of pharmacology that examines the role of genetics in drug response
  • Leads to idiosyncratic response - unpredictable and unexplained drug reactions
  • In the Future: Customised Drug Therapy-customised to match the genetic makeup of each patient (Personalised Medicine)
• The LD50 cannot be determined experimentally in humans, SO IT IS USED...?


  Median toxicity dose (TD50)
• Therapeutic index = TD50/ED50
• lower dose has a higher potency,

  but they have equal efficacy
• A drug with a low therapeutic index is less safe because there is little difference between the effective dose and the lethal dose.
• Morphine is more efficacious than aspirin and ibuprofen as it produces a higher maximal response
• Functional antagonists inhibit the effects of an agonist not by competing for a receptor, but by changing pharmacokinetic factors
• Drug + Receptor =?


  EFFECT
• Drug + Receptor = ? If drug is a full agonist


  Maximum Effect
• Drug + Receptor = ? If drug is a partial agonist


  Less than maximal effect
• Drug + Receptor = ? If drug is an antagonist (blocker) 


  Block effect
• • How to know if the standard dose is effective?


  Patient observation. Vital signs. Monitoring lab data