Pharmacology

• Pharmacology


  The study of drugs, their uses and how they affect organisms
• Pharmacokinetics

  Describes what the body does to a drug
• Pharmacodynamics

  Describes what the drug does to the body
• Drug


  Any chemical that can affect living processes
• Properties of an ideal drug

  • Effective
  • Safe
  • Selective
• Additional properties of an ideal drug

  • Reversible action
  • Predictability
  • Ease of administration
  • Freedom from drug interaction
  • Low cost
  • Chemical stability
• Chemical name

  Complicated, describes the chemical and physical properties of the drug
• Generic name


  Describes the active ingredient
• Trade name

  Assigned by the company marketing the drug
• Most drugs have three names: chemical, generic, and trade
• ADME

  Absorption, Distribution, Metabolism, Elimination
• Absorption


  • The drug absorption from the site of administration which permits the entry of the therapeutic agent into the plasma
• Distribution

  • Reversible process, the drug leaves the bloodstream and distributes into the interstitial and intracellular fluids
• Metabolism

  • Biotransformation of the drug into metabolites by the liver or other tissues
• Elimination

  • The drug and its metabolites are eliminated into urine, bile or feces
• Routes of Drug Administration

  • Enteral (Oral, Sublingual/Buccal)
  • Parenteral (Intravenous, Intramuscular, Subcutaneous)
  • Other routes (Inhalation, Intrathecal/Intraventricular, Topical, Transdermal, Rectal)
• Oral administration

  • Advantages: Easily self-administered, Low risk of systemic infections, Easier to manage toxicity

  Disadvantages: Complicated absorption, Inactivation of drugs due to first pass effect or stomach acidity
• Enteric coated

  • To protect the stomach (e.g. aspirin)

  To protect the drug from stomach acidity (e.g. omeprazole)
• Extended release

  • To control how fast the drug is released from the pill to the body

  Slow absorption and prolong the duration of action

  Less frequent dosage, improve compliance
• Sublingual/Buccal

  • Drug diffuses into the capillary network to the systemic circulation

  Advantages: Ease of administration/Convenience, Rapid absorption, Low incidence of infection, Bypass GI, Bypass first pass effect
• Parenteral route

  • Direct administration of the drug across body barriers into the systemic circulation

  Used for: Drugs with poor GI absorption, Drugs unstable in GI, Unconscious patients, Rapid onset of action, High bioavailability

  Advantage: No first pass metabolism, Provides the most control over the dose

  Disadvantages: Risk of infection, local tissue damage, pain, Can be irreversible
• Intravenous (IV)

  • Bolus: Immediate delivery of full amount

  Infusion: Delivery over a longer time
• Intramuscular

  • Aqueous solution (Rapid absorption)

  Depot preparation in nonaqueous vehicle
• Subcutaneous

  • Less risk of hemolysis or thrombosis (compared to IV)

  May provide sustained slow effect
• Inhalation

  • Rapid delivery across large surface area of mucous membranes
• Intrathecal/intraventricular

  • Direct injection into the cerebrospinal fluid

  Rapid delivery

  To avoid the blood brain barrier
• Topical


  • Application to the skin, for local effect
• Transdermal


  • Sustained delivery of drugs (e.g. nicotine patches)
• Rectal

  • Rapid delivery

  Rectal absorption is erratic and incomplete

  Used when oral administration is not possible (antiemetics)
• Factors that influence oral bioavailability

  • First-pass hepatic metabolism

  Nature of the drug formulation

  Solubility of the drug

  Chemical instability

  Decomposition in acidic gastric juices

  Decomposition by hydrolytic gut enzymes

  Degradation by gut microorganisms

  Food in the gut may alter absorption rate and amount

  Metabolism by gut wall enzymes
• First-pass metabolism


  When an oral drug is absorbed across the GI tract, it first enters the portal circulation before the systemic circulation

  If the drug is rapidly metabolized in the liver or gut wall, less of the active ingredient will reach the systemic circulation
• Mechanisms of drug absorption from GI tract

  • Passive diffusion

  Facilitated diffusion

  Active transport

  Endocytosis and exocytosis
• Factors influencing absorption

  • pH

  1. glycoproteins (P-gp)

  High expression of p-gp reduces absorption
• Drug Distribution


  • Depends on: Cardiac output and regional blood flow, Capillary permeability, Tissue volume, Drug-protein binding in plasma and tissues, Hydrophobicity of the drug
• Blood Flow


  • Unequal distribution of cardiac output, variable rate of blood flow to tissue capillaries

  Blood flow to the brain, liver and kidney is greater than that to skeletal muscles

  Adipose tissue, skin and viscera have lower rates of blood flow
• Drug-Protein binding


  • Binding to plasma proteins

  Binding to tissue proteins, can accumulate in tissues due to tissue protein binding
• Plasma Half-Life (t1/2)


  Length of time needed to decrease drug plasma concentration by one half

  The greater the half-life of the drug, the longer it takes to excrete

  Determines frequency and dosages
• Drug clearance through metabolism

  • Routes of elimination include: Hepatic metabolism, Elimination in bile, Elimination in urine

  Metabolism leads to products with increased polarity which allows drug elimination
• Metabolism Kinetics


  1. First-order kinetics: The rate of drug metabolism and elimination is directly proportional to the drug concentration

  2. Zero-order kinetics (nonlinear kinetics): The rate of metabolism or elimination is constant and does not depend on drug concentration
• Reactions of Drug Metabolism

  • Phase I: Oxidation, Reduction, Hydrolysis

  Phase II: Conjugation