Pharmacology Lecture 4

• What is the main process by which the body eliminates unwanted substances?

  Drug excretion
• What are the two most common routes of drug excretion?

  Biliary and renal
• Why might lipophilic drugs require several metabolism steps before excretion?

  To increase their water solubility
• Which organ is quantitatively the most important route for excretion of parent drugs and metabolites?

  Kidney
• What process does the kidney use to excrete parent drugs and metabolites into urine?

  Active secretion
• Which organ is important for the excretion of a number of drugs via active secretion into bile?

  Liver
• Which of these plays a minor role in drug excretion?

  Sweat
• How do other routes of excretion, like sweat and tears, contribute to drug elimination?

  Via passive diffusion
• What is the primary way drugs are eliminated from the body?

  By the kidneys
• What are the principal renal mechanisms involved in the excretion of drugs?

  • Glomerular filtration
  • Active tubular secretion
  • Passive tubular reabsorption
• How do glomerular filtration and active tubular secretion affect drug concentration in the kidney lumen?

  Increase it, facilitating excretion
• What happens to drugs that are excreted into the urine?

  They are eliminated from the body
• How does tubular reabsorption affect drug concentration in the kidney lumen?

  Decreases drug concentration
• What does tubular reabsorption do?

  Prevents drugs from being excreted
• How does pH affect the ionization of drugs?

  pH affects ionization
• Why are ionized drugs less effectively reabsorbed from the loop of Henle?

  They are more polar
• When can the renal elimination of ionizable drugs be increased or decreased by altering urine pH?

  When their pKa is within urinary pH range
• How does urine pH affect the proportion of a drug that is excreted in urine?

  It affects ionization
• What kind of drug is phenobarbital?

  Weak acid
• What are phenobarbital's properties?

  Potent sedative and anticonvulsant
• How does alkalinization of the urine affect phenobarbital excretion?

  Increases renal excretion
• Why is alkalinization of urine used in phenobarbital overdose treatment?

  To increase its renal excretion
• What factors affect the renal excretion of a drug?

  • Molecular weight
  • Lipophilicity
  • Volume of distribution
  • Plasma protein binding (PPB)
  • Ionisation
  • Age
  • pH
  • Disease
• What kind of drug is amphetamine?

  Weak base
• How does acidification of urine affect amphetamine excretion?

  Increases its excretion
• Why would athletes use amphetamine?

  To enhance performance
• How does acidification of urine increase amphetamine excretion?

  By increasing its ionization
• What is clearance?

  Hypothetical volume of fluid cleared of drug
• What are the units of clearance?

  mL/min
• What is the formula for clearance?

  CL = Elimination rate/Plasma drug concentration
• What does clearance represent?

  Rate of drug elimination relative to plasma conc
• What processes contribute to clearance?

  Filtration, secretion, and reabsorption
• What is half-life?

  Time to eliminate 50% of the drug
• What is the purpose of half-life?

  Determines dosing frequency for therapeutic levels
• What is the formula for half-life?

  $t1/2=$$0.693 Vd/CL$
• What does distribution half-life refer to?

  Time for 50% of drug to distribute
• How are clearance and volume of distribution related?

  Inversely related
• How does a large volume of distribution affect drug excretion in urine?

  Poorly excreted
• What type of drugs show higher clearance rates?

  Drugs contained in the blood compartment
• Why can't drugs bound to plasma proteins be filtered by the glomerulus?

  They are too large