Drug Actions and Handling by the Body - Pharmacokinetics

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Drug Actions and Handling by the Body -
Pharmacokinetics

• David Henry

Discipline of Clinical Pharmacology
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Introduction What we will cover

• How do drugs act and how are they handled by the
  body?
• Drug Action, Drug Absorption, Drug Distribution
  and Drug Elimination
• The application of these principles to the ways
  in which drugs are used in treating patients

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Drug Action

• Drugs tend to be small lipid-soluble molecules
• Drugs must get access to sites of action
• Drugs tend to bind to tissues, usually protein
  molecules
• Drugs alter the actions of enzymes, ion channels
  and receptors

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Overview of Drug Action

• ENZYME example Angiotensin Converting enzyme
  inhibitors ACE I ----X----------gtACE
  II lowered ACE II -----gt Reduced BP
• ION CHANNELS example Local Anesthetics Bloc
  k Na channels---gtAnesthesia

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• Receptor Binding
• Receptors are specialised binding sites - often
  on cell surface- which have specificity for
  certain substances (incl drugs). Drugs may
  activate or block the receptor
• Activation of the receptor changes the activity
  of the cell eg adrenaline activates the beta 1
  receptors in the heart and speeds up the heart
• Drugs have selectivity for receptors eg
  Histamine2 antagonists- reduce histamine-induced
  acid secretion and heal peptic ulcers

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Pharmacokinetics

• The action of the body on the drugs
• The way the body handles drugs determines the
  dose, route and frequency of administration
• The handling of drugs by the body can be split
  into absorption, distribution and elimination

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Pharmacokinetics

• Rate of absorption determines the time to the
  peak concentration
• The extent of absorption determines the height of
  the peak concentration

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Pharmacokinetics

• The fraction absorbed after oral dosing can only
  be obtained from a comparison of oral and IV
  dosing
• F AUCo AUCiv

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• High First Pass Clearance
• Reduces the height of the peak
• Propranolol a beta- blocking drug has a high
  first pass clearance

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Pharmacokinetics

• The pattern of concentrations after IV dosing
  often follows a series of exponential functions
  reflecting distribution and ultimately
  elimination of the drug

T1/2
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Multiple Dosing
Approx 5 half-lives to reach steady state
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Summary

• State what has been learned
• Define ways to apply training
• Request feedback of training session

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Where to get more information

• Other training sessions
• List books, articles, electronic sources
• Consulting services, other sources