<aside> 💡 Intro to Pharmokinetics

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• LO1 describe the main routes of administration, their advantages and disadvantages

  • Pharmacokinetics
    • Relationship between dose and drug concentration at site of action
    • Time course of drug concentration in the body
  • The concentration that a drug reaches at its target is by the rate and extent of:
    • Absorption
    • Distribution
    • Metabolism
    • Excretion
  • Absorption
    • Process by which drug enters body
    • Determines magnitude and time of onset
    • Enter circulation either directly or absorbed from site of administration
      • Tablets, capsules, liquids
      • Enteric-coated preparations
        • most drugs are absorbed in the small/large intestine —> need to pass through stomach = coated
      • Sustained release preparation
      • Topical preparations
      • Injectable liquids
  • Oral administration
    • Mouth and GIT
    • Chemical factors:
      • Formulation, physical properties
      • Ionisation, solubility in aqueous & lipid phases
    • Physiological factors:
      • pH of the GI contents
      • GI motility
      • Disorders
      • drugs
      • presence of food
      • Metabolism of the drug by GI enzymes
      • Splanchnic (GIT) blood flow
      • First pass metabolism
  • Parenteral = by injection
    • Intravenous administration
      • Thiopentone (anaesthetic)
      • Injection
      • Advantages:
        • Almost immediate effect
        • Used for oral drugs that will be broken down by first pass metabolism
      • Disadvantages:
        • Difficulty of administration
        • Potential risk of overdose
        • Thrombosis
        • Infection
    • Subcutaneous or intramuscular administration
      • Slower, longer duration
      • Intramuscular injection can be painful and is dependent on local blood flow
      • Insulin (diabetes mellitus)
    • Intrathecal
      • Epidural
      • Injection into subarachnoid space of spinal cord
      • Example: bupivacaine in labour
  • Inhalation
    • Inhalation: Anaesthetics
    • Drugs whose site of action is the lungs (bronchodilators)
  • Epithelial
    • Skin, cornea, nasal mucosa
    • Local effect
    • Transdermal stick-on patches
    • Lipid soluble drugs
    • Example: oestrogen patches (hormone replacement therapy)
    • Sublingual
    • Administration via the oral cavity allows for rapid absorption directly into the systemic circulation without passage through the liver
    • Example: glyceryl trinitrate (angina)
  • Rectal
    • Drugs which produce a local effect on the GI tract
    • Or when oral or intravenous administration not possible
    • Example: anti-inflammatory drugs for inflammatory bowel disease

• LO2 explain the main factors that affect drug absorption, including effects of pH on ionisation

  • Factors affecting absorption
    • Lipid solubility
    • Ionization
  • Lipid solubility
    • To reach target tissues, drugs must cross lipid membrane
    • Mainly by diffusion or by carrier-mediated transfer
  • Ionization
    • Many drugs weak acids/weak bases
    • Can be ionised or non-ionised
    • Ionised form (charged polar) water-soluble
    • Unionised form (non-polar) more lipid soluble
    • Ionisation determined by pH of environment in which drug dissolves
  • Ionization
    • Will be ionized if pH opposite to pKa
    • Acidic drugs ionised with higher pH (basic environment)
    • Basic drugs ionised with lower pH (acidic environment)
    • Strong bases > pKa 10 poorly absorbed because fully ionised
    • Strong acids < pKa 3 poorly absorbed because fully ionised
  • Henderson Hasselback equation

• LO3 define the term "volume of distribution" and explain how it is used

• LO4 describe the role of the liver in drug metabolism, and describe the properties of phase I and II metabolism

• LO5 describe the factors that affect drug metabolism, and explain the impact of these on plasma drug concentrations

• LO6 define the terms clearance and bioavailability, and explain how bioavailability is measured

• LO7 name the major routes of excretion

• LO8 define "half life" and explain its relation to clearance and volume of distribution

• LO9 apply basic ADME concepts to interpret drug pharmacokinetic information