Lecture 01

• What does ADME stand for in pharmacokinetics?

  Absorption, Distribution, Metabolism, Excretion
• How do alterations in ADME parameters affect drugs?

  They alter drug availability in the body
• What is the primary site of absorption for oral drugs?

  Gastric mucosa
• What is the absorption site for suppositories?

  Rectal membranes
• Which route is used for nitroglycerin in angina treatment?

  Sublingual (under the tongue)
• What is the absorption site for pessaries?

  Vaginal membranes
• What is the absorption route for transdermal patches?

  Skin
• What is the absorption site for inhaled drugs?

  Pulmonary epithelium
• What is absorption in pharmacokinetics?

  Movement of a drug into the blood
• How are most drugs absorbed?

  By passive absorption
• What type of molecules diffuse more rapidly?

  Small molecules
• Which type of drugs are absorbed faster?

  Lipid soluble, non-ionised drugs
• What does passive diffusion depend on?

  Size and ionisation of the molecule
• What factors affect gastric emptying time?

  • Type of food
  • Type of activity
  • Drug formulation
• Where are drugs more efficiently absorbed?

  In the small intestine
• What is the typical transit time through the small intestine?

  3-4 hours
• What is the range of colonic transit time?

  8 hours to 5 days
• How do solutions and suspensions compare in absorption speed?

  They empty and are absorbed more rapidly
• What happens to larger pieces of material in the stomach?

  They are broken down and dissolved
• What factors contribute to biological variability in gastric emptying?

  • Greater motility increases absorption
  • Fasting conditions preferred in trials
  • Some drugs taken with food to prevent irritation
• What increases gastric emptying?

  Administration of large volumes of liquid
• What effect do alkaline solutions have on gastric emptying?

  They increase gastric emptying at low concentrations
• What decreases gastric emptying?

  Ingestion of food, especially fatty foods
• What is the effect of physical inactivity on gastric emptying?

  It decreases gastric emptying
• What disease state can decrease gastric emptying?

  Pyloric stenosis
• How does emotional state affect gastric emptying?

  Stress increases gastric emptying
• What factors affect oral absorption of a drug?

  • Disintegration of dosage form
  • Dissolution of particles
  • Chemical stability of drug
  • Stability to enzymes
  • GI tract motility and mixing
  • Presence and type of food
  • Blood flow to GI tract
  • Gastric emptying time
• What does the Law of Mass Action state?

  The rate of reaction is proportional to masses
• What is first-order kinetics in pharmacokinetics?

  Rates are proportional to drug concentration
• What is absorption half-life (t1/2)?

  Time to increase plasma concentration by 50%
• What is elimination half-life (t1/2)?

  Time to reduce plasma concentration by 50%
• What are the methods of membrane permeation by drugs?

  • Direct diffusion through lipid
  • Ionisation (non-ionised can pass)
  • Carrier-mediated transport
  • Diffusion through aqueous pores
  • Pinocytosis
• How does ionisation affect drug absorption?

  Non-ionised drugs pass through membranes
• What is the pH of the mouth?

  Neutral
• What is the pH range of the stomach?

  2-6
• What is the pH range of the small intestine?

  6-8
• What is the pH range of the colon?

  5.5-7
• What factors affect oral drug absorption?

  • Passive transfer relies on ionisation
  • Non-ionised forms are lipid soluble
  • Strong bases poorly absorbed
  • Strong acids fully ionised
• What are the physiochemical properties of drugs affecting absorption?

  • Too hydrophilic (e.g. atenolol)
  • Too lipophilic (e.g. acyclovir)
  • Balance of lipophilicity and hydrophobicity
• How does ionisation depend on pH?

  It depends on the drug's dissociation constant