BIO2118

• The 2 main arms of pharmacology

  • Pharmacodynamics (PD)
  • Pharmacokinetics (PK)
• Pharmacodynamics (PD)


  • "what the drug does to the body"
  • The biochemical, physiologic, and molecular effects of drugs on the body
  • Chemical interactions, receptors, signal transduction, etc.
• Pharmacokinetics (PK)


  • "what the body does to the drug"
  • The movement of a drug into, through, and out of the body
  • Liberation, absorption, distribution, metabolism, excretion, toxicity
  • Half-life (t½), bioavailability, etc.

  
• Drug sources


  • Plants
  • Animals
  • Microorganisms (fungi, bacteria)
  • Minerals
  • Synthetic
  • Recombinant proteins
• Drug Classes


  • By makeup: Hormone, Carbohydrate
  • By action: Beta blockers, ACE Inhibitors
  • By therapeutic affect: Antiarrhythmics, Antianginals
  • By system/target (systems pharmacology): Drugs affecting the CNS, Drugs affecting the ANS, Drugs used to treat cardiovascular system, Drugs affecting other systems (Respiratory, Hormones, GI)

  
• Names of a drug

  • Chemical name
  • Generic name (non-proprietary)
  • Brand or trade name (proprietary)
• Drug Schedules

  • Schedule 1: (not used)
  • Schedule 2: Pharmacy medicine
  • Schedule 3: Pharmacist only medicine
  • Schedule 4: Prescription only medicine
  • Schedule 5: Caution
  • Schedule 6: Poison
  • Schedule 7: Dangerous poison
  • Schedule 8: Controlled drug
  • Schedule 9: Prohibited substance
  • Schedule 10: Dangerous substances (prohib.)
• Drug interaction with the body (a drugs life cycle)

  1. Administration – getting the drug in

  2. Absorption – drug gets into bloodstream

  3. Distribution – blood carries drug to tissues

  4. Drug action – eg. drug binds & affects cells

  5. Termination of effect, metabolism and/or elimination

  
• First pass metabolism


  • Most of drugs absorbed from the GI tract enter the portal (liver) circulation before they are distributed to the systemic (general) circulation
  • The drug will be metabolized in the liver before reaching the target organ, decreasing drug efficacy
• 5(+) 'Rights' of Safe Administration

  • Right patient
  • Right drug
  • Right dose
  • Right time
  • Right route
  • Right documentation
  • Right to refuse
  • Right education
  • Right assessment/reason
  • Right evaluation/response
• How do drugs work?

  • Transport systems: eg. ion channels, carriers
  • Enzymes: eg. block/prevent enzyme activity
  • 'non-specific': eg. chelation, antacids, osmotics
  • Receptors
• Receptor


  • Any biological molecule that receives chemical signals and is responsible for transducing extracellular signals into intracellular responses
  • Binds to receptor, initiates intracellular signal, resulting in a response/effect

  
• Receptor types & action

  • 4 families/classes of receptor
  • Mediate different effects
  • Different response time

  
• Factors altering drug response

  • Age
  • Body mass
  • Gender
  • Time of administration
  • Pathologic state
  • Genetic factors
  • Psychological factors

  
• Pharmacokinetics


  • The study of the basic processes that determine the duration and intensity of a drug's effect
  • The movement of a drug into, through, and out of the body
  • "what the body does to the drug"
  • Four (6?) principles (ADME or LADMET): (Liberation), Absorption, Distribution, Metabolism, Elimination, (Toxicity)

  
• Relationship of Administration Route to ADME

  • Enteral (slow): Oral, Rectal, Through mucus membranes
  • Parenteral (fast): injection, Inhalational
• Absorption


  • Absorption refers to how medicines enter the bloodstream (plasma)
  • Absorption rate is dependant on route of administration
  • Also influenced by: Concentration gradient (hilow), Drug size (must be < 1kDa), Lipid solubility / pH

  
• Fast and slow – enteral versus parenteral


  • Enteral (slow): Orally (swallowed), Rectally (suppository), Through mucus membranes
  • Parenteral (fast): injection, Intravenous (IV), Intramuscular (IM), Subcutaneous (SC), Intraperitoneal (IP), inhaled (through lungs)
• Absorption & drug solubility

  • Water-soluble: Ionised (have electrical charge), Crosses through pores in capillaries, but not cell membranes
  • Lipid(fat)-soluble: Non-ionised (no electrical charge), Crosses pores, cell membranes, blood-brain-barrier
• Bioavailability


  The fraction of an (orally or enteral) administered dose that reaches the systemic circulation as intact drug, taking into account both absorption and local metabolic degradation (first-pass)

  
• Distribution


  • The reversible transfer of a drug from the bloodstream to the tissue
  • Drug moves between different body compartments
  • Drug reaches the site of action (receptors)
  • The degree of distribution of a medicine depends on its physical and chemical properties

  
• Protein binding


  • Drugs reversibly & rapidly bind plasma (blood) proteins
  • Protein bound drug is pharmacologically inactive
  • Only free drugs can bind to their receptors
• Body fluid compartments & volume of distributionThere are several physiological fluid compartments into which drugs can distribute

  • The volume of distribution (VD) is the theoretical volume necessary to contain the total amount of drug in the body at the same concentration as that in the plasma

  
• Volume of Distribution


  • Vd = amount of drug (in body) / plasma concentration
  • Magnitude of Vd indicates the extent of drug distribution in the body, but not the location
• Metabolism


  • Metabolism is the irreversible conversion of one chemical compound into another
  • Most metabolism of drugs occurs in the liver, but also in the gut wall, lungs, and blood plasma
  • First-pass effect allows the liver to metabolise or deactivate medicines and potentially harmful substances before they are distributed throughout the body
  • The main enzymes involved belong to the cytochrome P450 group

  
• Excretion


  • Refers to how the body gets rid of a medicine or its metabolites
  • Main routes of elimination: Excretion by kidneys, Excretion in faeces

  
• Metabolism


  The irreversible conversion of one chemical compound into another
• Metabolism of drugs


  • Most metabolism occurs in the liver, but also in the gut wall, lungs, and blood plasma
  • First-pass effect allows the liver to metabolise or deactivate medicines and potentially harmful substances before they are distributed throughout the body
  • Liver hepatocytes contain the necessary enzymes for metabolism
  • The main enzymes involved belong to the cytochrome P450 group

  
• Excretion


  How the body gets rid of a medicine or its metabolites
• Main routes of elimination

  • Excretion by kidneys
  • Excretion in faeces
• Clearance (CL)


  Reflects the elimination of the drug from the body & is related to the plasma concentration (Cp) and dose rate
• Clearance


  • It is the collection of processes by which the body removes the drug from the body & occurs via two key ways: Metabolism & elimination
  • It is a very important parameter as it defines how much drug should be administered, and how frequently to dose a patient (dose rate)

  
• Zero-order kinetics


  Rate of elimination is constant, independent of drug concentration, constant amount eliminated per unit of time
• First-order kinetics


  A constant fraction of drug is eliminated per unit of time, when drug concentration is high, rate of disappearance is high
• Half-life (t1/2)


  The time it takes to remove half the current concentration of the drug from the body
• Volume of distribution (Vd)

  The higher the Vd, the less a drug is contained in the plasma, so its half-life is longer
• Pharmacology is the study of what drugs do and how they do it
• Key components of pharmacology

  • Drug classes, naming and classification
  • Routes of administration – enteral vs parenteral (and why)
  • Drug action and the importance of receptors
• Pharmacokinetics


  "What the body does to the drug"
• Key components of pharmacokinetics

  • ADME (absorption, distribution, metabolism, elimination) and factors affecting these
  • Bioavailability, volume of distribution, clearance, half-life