Lecture 02, 3

• What is the definition of volume of distribution (Vd)?

  Theoretical volume needed to distribute a drug
• How is the volume of distribution (Vd) calculated?

  By measuring drug concentration in serum
• What are the various compartments into which drugs are distributed?

  Plasma, interstitial fluid, and cells
• What factors affect drug distribution?

  Blood flow, lipid solubility, plasma protein binding
• What is the effect of blood flow on drug distribution?

  Higher blood flow increases drug distribution rate
• What are the special barriers to drug distribution?

  Blood-Brain Barrier and Placenta
• How does lipid solubility affect drug distribution?

  More lipid-soluble drugs distribute better
• How does plasma protein binding influence drug distribution?

  Bound drugs are usually inactive and less distributed
• What is the distribution pattern in well-perfused tissues?

  High blood flow in kidneys, heart, lungs, brain
• What is the distribution pattern in slowly perfused tissues?

  Fat has a slow perfusion rate
• How do weak acids and bases exist in the body?

  As charged and non-charged forms based on pH
• What does the partition coefficient indicate?

  How lipophilic the drug is
• What is the total body water as a percentage of body weight?

  Varies from 50% to 70%
• What is the extracellular fluid composition?

  Blood plasma, interstitial fluid, lymph
• What is the significance of a high volume of distribution (Vd)?

  Indicates drug is mostly in tissues
• What factors contribute to a low volume of distribution (Vd)?

  Polar, low lipid solubility, ionised drugs
• What is the use of volume of distribution in clinical practice?

  Planning dose regimens and calculating loading dose
• How does obesity affect volume of distribution?

  Increases Vd for fat-soluble drugs
• How does pregnancy affect volume of distribution?

  Increases blood volume and Vd for drugs
• What is the role of albumin in plasma protein binding?

  Most important binding protein for acidic drugs
• What is the normal range of albumin in plasma?

  3.9 – 5.5 g per 100 ml
• How do basic and acidic drugs bind to albumin?

  Basic drugs bind high capacity, low affinity
• What clinical problems arise from plasma protein binding?

  Competition for binding sites can cause toxicity
• What happens when a drug displaces another from albumin?

  Can increase free drug concentration and toxicity
• What is first-pass metabolism?

  Metabolism before drug reaches systemic circulation
• How can first-pass metabolism be overcome?

  By administering drugs through IV
• What are the two major ways metabolism changes a drug?

  Reduces lipid solubility and alters biological activity
• What are Phase I reactions in drug metabolism?

  Oxidative and reductive reactions altering drug structure
• What is the role of cytochrome P450 in metabolism?

  Enzyme involved in Phase I metabolism
• What are Phase II reactions in drug metabolism?

  Conjugation reactions making drugs more water-soluble
• What is enzyme induction in drug metabolism?

  Increased metabolism due to co-administered drugs
• What are the results of inhibition of drug metabolism?

  Increased plasma drug levels and potential toxicity
• What is the elimination half-life of a drug?

  Time to reduce plasma drug concentration by half
• What is a zero-order process in drug elimination?

  Constant elimination rate regardless of concentration
• What is the significance of the area under the curve (AUC)?

  Indicates total drug exposure in the body
• What is a maintenance dose?

  Repeated dose to maintain steady-state concentration
• What are the phases of drug metabolism?

  • Phase I: Oxidative and reductive reactions
  • Phase II: Conjugation reactions
• What are the routes of drug excretion?

  • Kidney
  • Lungs
  • Liver, bile
  • Faeces
  • Breast milk
  • Tears, saliva, sweat
  • Hair
• What is the therapeutic window?

  • Range of drug concentration
  • Desired effects vs. unwanted effects
• What is the significance of steady state in pharmacokinetics?

  • Equilibrium point of drug administration
  • Amount administered equals amount excreted