pharmacokinetics and pharmacodymanics

• pharmacokinetics


  is the study of what the body does to a drug
• pharmacodynamics 


  is what a drug does to the body
• absorption of drugs

  Rate of absorption into systemic circulation depends on:

  Route of administration

  • Oral - convenient, efficient, differences in pH. Subject to 1st pass metabolism
  • Buccal (via the cheek) - high blood flow, avoids 1st pass metabolism
  • Inhalation - large surface are and high blood flow
  • Rectal - reduced 1st metabolism
  • Topical - absorption through the skin
  • Intravenous/intramuscular/subcutaneous
• distribution of drugs

  Most important factors determining distribution:

  • Protein binding - e.g. plasma proteins, generally a drug is inactive whilst bound to plasma proteins 
  • Blood flow
  • Membrane permeation 
  • Tissue solubility

  Drugs need to cross cell membranes to produce their effects. Such transfer occurs more readily with a:

  • Low degree of ionization - particle charge
  • Low molecular weight
  • High lipid solubility 
  • High concentration gradient
• metabolism

  • Liver principal organ of drug metabolism
  • GI tract, lungs, skin, kidneys - can metabolize some drugs
  • Influenced by several factors
  • Metabolism may produce toxic metabolites

  Factors that influence drug metabolism

  • Genetics 
  • Age (metabolism impaired either end of age spectrum)
  • Gender
  • Liver size and function
  • Circadian rhythms
  • Body temperature
  • Nutritional state - e.g. take with/without food
  • Other medications - can increase/decrease rate of metabolism
• excretion

  • Kidneys - glomerular filtration and tubular secretion
  • Liver - some drugs secreted in bile e.g. cardiac glucosides. Enterohepatic reuptake
  • GI tract
  • Lungs - e.g. gaseous anesthetics
  • Minor routes - sweat, saliva and breast milk
• targets for drug action

  • Most drugs work by initially binding to a protein 
  • Many of these are involved in physiological regulation
  • Common protein targets include (RICE):
  • Receptors
  • Ion channels 
  • Carrier molecules
  • Enzymes
• enzymes

  • A protein (or protein-based molecule) that acts as a catalyst speed up a chemical reaction. Acts on specific substances known as substrates
  • Convert substrates into products
  • Accounts for a large number of drug actions

  Conversion of prodrugs

  • Many drugs given orally are in an inactive form
  • Rely on conversion by enzymes (normally in liver) into the active drug
  • Examples include: codeine, enalapril, dabigatran, gabapentin
• carrier molecules

  • Movement of substances across cell membrane 
  • often requires a carrier molecule (e.g. ions, glucose,  amino acids)
  • Some drugs can target these carriers and block transport
  • E.g. proton pump inhibitors (PPI e.g. omeprazole), cardiac glycosides (e.g. digoxin), Tricyclic antidepressants (TCA e.g. amitriptyline)
• ion channels

  • Over 100 types of ion channel
  • Important in systems that require rapid responses e.g. Nervous system, renal, CVS
  • Drugs either block or modulate channels
  • E.g. local anesthetics (lidocaine), amiloride, diltiazem, nicorandil, benzodiazepines