Lecture 2: Pharmacokinetics

• What is the main focus of pharmacokinetics?

  Distribution of drugs in the body
• What does reversible transfer of a drug refer to?

  Movement of drug between body compartments
• What factors affect drug distribution?

  1. Drug molecule characteristics
  2. Organs blood flow
  3. Binding with plasma/tissue proteins
  4. Organ barriers
• How much of lipophilic Thiopental is in fat tissue after 3 hours?

  70%

  
• Which organs receive the most drug delivery?

  Brain, liver, kidneys, lungs, heart
• What is the role of albumins in drug distribution?

  Major carrier for acidic drugs
• What type of drugs does alpha-1-acid glycoprotein bind?

  Basic drugs
• What is a characteristic of plasma protein binding?

  Reversible and non-specific binding
• What happens when proteins can be saturated?

  Dynamic equilibrium between bound and free drug

  
• What is the effect of competition between drugs for binding with plasma proteins?

  One drug can displace another

  
• What do bisphosphonates bind to in the body?

  Hydroxyapatite crystals in bones
• Where does gentamicin accumulate in the body?

  Kidneys and vestibular apparatus
• What does a large volume of distribution (Vd) indicate?

  Extensive distribution of the drug in tissues
• What is the blood-brain barrier (BBB)?

  A barrier that limits drug entry to the brain

  
• What increases the permeability of the BBB?

  Inflammation
• What is the significance of the placental barrier?

  Drugs should be taken only if vital
• How is volume of distribution (Vd) calculated?

  $Vd(L) =$$Q(dose) / Cp(plasma concentration)$
• What is the Vd for a patient with 210 mg of lidocaine and a plasma concentration of 3 mcg/ml?

  $70 L$
• What is drug metabolism?

  Biotransformation of the drug's molecule
• What is the purpose of drug metabolism?

  To generate more polar drug metabolites
• Where are drugs primarily metabolized?

  Mainly in the liver

  
• What catalyzes the chemical reactions in drug metabolism?

  Enzymes
• What are the phases of drug metabolism?

  1. Phase I: Oxidation, reduction, hydrolysis
  2. Phase II: Conjugating reactions
• What is the first-pass effect?

  Pre-systemic metabolism of drugs
• What is a prodrug?

  Inactive form activated by enzyme reaction
• What is the dominant process in phase II metabolism?

  Glucuronidation
• What is the role of UDP-Glucuronosyltransferases?

  Catalyze glucuronidation reactions

  
• What is the significance of acetylation in drug metabolism?

  Genetically determined metabolism of drugs
• What is enterohepatic recirculation?

  Reabsorption of drug in intestines

  
• What is the main way of elimination for water-soluble drugs?

  Renal excretion
• What is glomerular filtration?

  Passive process driven by hydrostatic pressure

  
• What can’t be filtered during glomerular filtration?

  Large molecules or bound drugs
• What is tubular secretion?

  Active transport of drugs/metabolites
• How does pH affect drug reabsorption?

  Ionized drug form can’t be reabsorbed
• What is the definition of clearance in pharmacokinetics?

  Plasma volume cleared of drug per minute

  
• What is plasma half-life (t1/2)?

  Time to reduce drug plasma concentration by 50%
• How many half-lives are required to eliminate a drug from plasma?

  4-5 half-lives