T2 L12: PK1 - Drug absorption

• What are the '6 rights of prescribing'?

  • right patient
  • right drug
  • right route
  • right dose
  • right time
  • right outcome
• What is pharmacokinetics?


  what the body does to the drug

  Facilitates safe and effective use of medicines

  Determines optimal dosage regimen (dose, route, dose interval, duration of treatment)

  Predicts potential drug interactions
• What are the 4 areas of pharmacokinetics?

  Absorption

  Distribution

  Metabolism

  Excretion
• What is absorption in relation to pharmacokinetics?

  Drug transfer from its site of administration to the systemiccirculation (blood)
• What are routes of drug administration?

  Enteral: oral, rectal

  Sublingual

  Buccal
• What are the factors that influence enteral absorption?

  Gastrointestinal (GI) motility

  Absorptive area GI blood flow

  Drug particle size and formulation

  Drug physicochemical properties

  Drug binding
• What are the two important drug physiochemical properties?

  solubility

  pH
• What is the relationship between lipid, water solubility and drug absorption?

  The more lipid soluble a drug the greater the absorption

  The more water soluble a drug the less the absorption
• How does pH affect drug absorption?

  Acidic Drugs are better absorbed in acidic media

  Basic Drugs are better absorbed in basic media
• How does pH affect excretion?

  Acidic drugs are better excreted in basic media

  Basic drug better excreted in acidic media
• What is parenteral drug administration?

  routes other than digestive tract

  
• What are other routes of drug administration?

  • Topical: specific part
  • Transdermal: across skin
  • Inhalational: breathing
  • Intrathecal: through spinal canal
• The ideal dosing of a drug is...

  Between the MEC (minimum effective concentration) and MTC (minimum toxic concentration)

  
• A 21-year-old woman has recently been diagnosed withCrohn’s disease. She is on the combined oral contraceptivepill daily. Is there an increased chance of her becoming pregnant?

  Yes

  Crohn's disease affects absorption throughout the gut

  oral contraceptive pill may not be absorbed
• What is bioavailability?

  fraction of the administered dose of a drug that reaches the systemic circulation

  
  

  The concept: If a drug has an oral bioavailability of 20%, the oral dose needed for therapeutic effectiveness will need to be approximately 5

  times higher than the corresponding IV dose.

  
• How is the bioavailability graph of contraception drugs?

  red line - any absorptive disorder

  
• A 64-year-old man is admitted with decompensated congestive heart failure. A decision is made to administer furosemide. What is the most suitable route of administration?

  IV
• A 58 year old woman is admitted with severe community acquired pneumonia and she is to be treated with antibiotics. What is the most appropriate route of administration?

  doxycycline

  IV as severe

  no time for oral treatment as patient can deteriorate
• A 79 year old woman is prescribed alendronic acid for osteoporosis. Why is she asked to take the drug at least 30 minutes before breakfast or any other oral medicine?

  low bioavailability of alendronic acid

  if anything else in gut, bioavailability further decreases

  
• What is First pass (pre-systemic) metabolism?

  refers to metabolism of the drug prior to reaching systemiccirculation (hepatic extraction ratio)

  if big first pass effect, low bioavailability

  
• A 66 year old man takes sublingual glyceryl trinitrate (GTN)for stable angina. Justify this route of drug administration?

  GTN has huge hepatic extraction ratio so not effective to give orally

  all will go into liver and none into circulation

  + to bypass the absorptive process by the gut and get the drug instantly into circulation

  
• A 66-year-old man is takes propranolol for hyperthyroidism. Recent blood results indicate deranged liver function tests. Why might this be a concern?

  Propranolol undergoes significant first-pass hepatic effects

  concentration increases to toxic levels in liver

  
• What is bioequivalence?

  Two drugs are considered bioequivalent when:

  • there is no significant difference in the rate or extent of bioavailability
  • at the same molar dose and
  • under the same conditions

  Relevance:

  • Different formulations from different companies
  • Different batches of drugs from the same company