Introducing Pharmacokinetics and Pharmacodynamics

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Introducing Pharmacokinetics and Pharmacodynamics

• Janice Davies
• Pharmacist
• Room 23 Maudland Building
• JADavies5_at_uclan.ac.uk

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eLearn
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DVD

• Any problems / questions?

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Learning outcomes

• Define and discuss pharmacokinetic factors
• Discuss the factors that affect absorption,
  distribution, metabolism and excretion-how they
  affect drug therapy
• Define and discuss pharmacodynamic mechanisms of
  drug actions
• Apply pharmacokinetic and pharmacodynamic
  concepts to patient scenarios.

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Definitions

• Pharmacokinetics is what the body does to the
  drugs, for almost all drugs the magnitude of
  pharmacological effect depends on its
  concentration at its site of action.
• Pharmacodynamics is what the drug does to the
  body, ideally including
• the molecular mechanism (s)
• by which the drug acts

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PHARMACOLOGY

• PHARMACODYNAMICS
• (SPECIFIC TO DRUG OR DRUG CLASS)

• PHARMACOKINETICS
• (NON-SPECIFIC, GENERAL PROCESSES)

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Arrange the phrases!!! Factors determining
response of a patient to a drug

• Drug interactions
• Duration of effect
• Unwanted effects
• Reduction in symptoms
• Modification of disease progression
• Accumulation on repeat dosage
• Absorption from the site of administration
• Elimination from the body
• Delivery to the site of action
• Effects at the site of action
• Interaction with cellular component

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Pharmacokineticsconsidering such terms as

• Route
• Absorption
• Distribution
• Hepatic Metabolism
• Metabolic products
• Protein Binding
• Renal Excretion
• Half-life
• Toxicity

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Absorption
Distribution
Metabolism
Excretion
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Absorption
Distribution
Route
Enteral
Parenteral IV
Topical
oral
sublingual
transdermal
inhalation
Absorption
Absorption
Systemic circulation
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Absorption

• Process of drug movement from the administration
  site to the systemic circulation.
• The amount and rate of absorption are
• determined by several factors
• Physical nature of the dosage form
• Presence or absence of food in the stomach
• Composition of the GI contents
• Gastric or intestinal pH
• Mesenteric blood flow
• Concurrent administration with other drugs

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Bioavailability

• Bioavailability is the proportion of the
  administered dose that reaches the systemic
  circulation.
• Dale and Haylet, Pharmacology Condensed. 2004
• Refers to the amount and the rate of appearance
• of the drug in the blood after administration
  in
• its initial dose form
• Orally administered drug bioavailability is
  directly related to the individual solubility in
  body fluids.
• Poor solubility low
  bioavailability

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Effect of Food

• Bioavailability of some drugs is affected by the
  presence of food. E.g penicillin's, erythromycin,
  rifampicin, thyroxine
• Some drugs are taken before meals to allow time
  for drug to act before food is taken
• Gastric irritation can be caused by drugs taken
  on an empty stomach
• Effect of food on the absorption of drugs

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First Pass Effect

• Drugs that are absorbed via the GIT are
• circulated to the liver first via
• the hepatic portal vein
• Liver then acts as a filter
• Only part of the drug is
• circulated systemically
• The combination of
• processes is termed
• the First Pass effect

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Absorption animation

• http//www.youtube.com/watch?vxiuWdJYyIKs

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Distribution
Absorption
Metabolism
Factors affecting
Low albumin
Problems withHeart Circulation Diabetes
Bound drugs are pharmacologically inactive
because the drug-protein complex is unable to
cross cell membranes.
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Metabolism

• Drugs are metabolised in the liver, lungs,
• kidneys, blood and intestines.
• In order for drugs to pass across the lipid cell
  membrane they must be lipophilic
• The higher the solubility in lipids compared to
  water, the more rapid the tissue entry
• Metabolic rate determines the duration of the
  action of the drugs

Which BNF appendix relates to patients ability
to metabolise?
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Excretion

• Drugs are primarily excreted by the kidneys
• In order for drugs to be excreted
• they need to become hydrophilic
• Excretion of drugs can be affected
• by the urinary pH
• How the drug is excreted can
• influence prescribing decisions

Which BNF appendix relates to patients ability
to excrete?
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Half Life of Drugs

• Drug excretion is commonly expressed in terms of
  half life (t1/2)
• This is the time required for the concentration
  of the drug in the plasma to decrease by one-half
  of its initial value
• Drug half life is variable and can be long or
  short
• Subsequent doses are given to raise the
  concentration levels to a peak
• In theory, the optimal dosage interval between
  drug administration is equal to the half-life of
  the drug

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Example

• Drug 100mgs with a 6 hour half life
• 1st dose 100 mgs
• 2nd dose 100mgs 50 mgs still present 150mgs
• 3rd dose 100mgs 75 mgs still present 175mgs
• 4th dose 100mgs 88mgs still present 188mgs
• 5th dose 100mgs 94mg still present 194mgs
• 6th dose 100mgs 97mg still present 197mg
• As can be seen, accumulation becomes less at
• each dose- steady state is achieved after 3 to
  5 half lives.

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Loading Doses

• Are used when the medical condition demands high
  concentrations very quickly
• This is achieved by an initial dose that is twice
  the maintenance dose

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Some exam style MCQs
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Which ONE of the following affects absorption?

• Drug formulation
• Time of administration
• Mode of action of the drug

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A patient with renal impairment, taking a renally
excreted drug, will require which ONE of the
following?

• Dose reduction
• Dose increase
• Same dose

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Which ONE of the following describes
bioavailabilty?

• The proportion of drug reaching the circulation
• The extent of first pass metabolism
• The quantity of drug absorbed in the GI tract

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Tea break

• http//www.youtube.com/watch?vtnnoPedWO7M
• best to leave now if easily offended!

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Pharmacodynamics

• is the detailed study of the mode of action of
  drugs in the body or how drugs exert their
  effect at a cellular level
• Receptors
• Ion channels
• Enzymes
• Carrier molecules
• Chemotherapy

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Considering

• Receptors-agonist, partial agonist and antagonist
• Ion channels-gating of intracellular ions
• Enzymes-drugs act to inhibit or potentiate
• Carrier molecules-allow molecules not lipid
  soluble to cross cell membrane
• Chemotherapeutic agents
• Drug tolerance/dependence
• Effects of pathological state and biological
  variability

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Receptors

• Receptors are a target molecule that a drug
  molecule has to combine with to produce a
  specific effect
• Receptors must be compatible like 2 pieces of a
  jigsaw e.g. neurotransmission
• Main types of action at receptor
• Receptor agonists
• Receptor antagonists

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Types of receptors

• G-protein-couple receptors, seconds
• e.g. Muscarinic ACh receptors, adrenoceptors,
  histamine receptors
• http//www.ouhscphysio.org/humanphys/animations/g-
  protein_coupled_receptors.gif
• Kinase linked receptors, hours
• e.g. Insulin, Growth factor
• Nuclear intracellullar receptors, hours
• e.g. steroid, thyroid hormone

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• Ion Channels
• Drugs act to affect cellular gating mechanism in
  cell wall
• Ligand-gated ion channels, milliseconds
• e.g GABA benzodiazepines, Nicotinic ACh
• http//www.ouhscphysio.org/humanphys/animations/li
  gand-gated.swf
• Carrier molecules
• Drugs act on carrier transporters which allow
  molecules, not lipid soluble to cross cell
  membrane
• http//www.ouhscphysio.org/humanphys/animations/fa
  cilitated_diffusion.swf

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Enzyme inhibitors

• An enzyme is a protein that can promote or
  accelerate a biochemical reaction with a
  substrate
• When the enzyme mistakes the drug for a
  substrate, a drug-enzyme interaction occurs
• This interaction could increase or decrease the
  rate of the biochemical reaction

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(No Transcript)
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Chemotherapeutic agents

• Cytotoxic drugs act by interfering with cell
  growth and division at different stages of the
  cycle
• Anti-infective drugs

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Bacterial Cell
Cell wall
Cell membrane
DNA
Metabolism of bacterial cell
Class 2 reactions
Class 1 reactions
Class 3 reactions
Nucleotides
Proteins RNA DNA
Precursor molecules
Glucose
Amino acids
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Physiological Variability

• Liver disease
• Chronic alcoholism
• Renal disease
• Allergy

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Exam Style MCQs

• A receptor antagonist
• binds to a receptor and activates it
• binds to a receptor without causing activation
• blocks an enzyme

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• The pharmacodynamics of salbutamol can be
  explained by its
• activity on enzymes
• activity on ion channels
• activity on receptors

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• Warfarin has a
• Narrow Therapeutic Index
• Wide therapeutic range
• Neither are important

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Write brief notes on any TWO of the following
modes of drug action

• Receptor agonists
• Receptor antagonists
• Action at enzymes
• Ion channels
• Carrier molecules
• Chemotherapy

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Short answer questions

• What is a narrow therapeutic index?
• What is bioavailability?
• What is half life?
• What is a loading dose?
• What is pharmacodynamics?

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Further reading

• Downie, George (2008) Pharmacology and medicine
  management for nurses George Downie, Jean Macke
  4th Edition , Edinburgh. Churchill Livingstone
• OR
• Trounce, J, Greenstein, B, Gould, D. Trounces
  Clinical Pharmacology For Nurses. 18th Edition
  Churchill Livingstone Edinburgh.
• British National Formulary www.bnf.org
• Rang Dale Ritter and Moore (2003) Pharmacology
  Churchill Livingstone Bath Press 5th edition
• www.emc.medicines.org.uk