Pharmacokinetiks and Pharmacodynamics

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Introducing
Pharmacokinetics and
Pharmacodynamics
Janice Davies
Pharmacist
Room 23 Maudland Building
[email protected]
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eLearn
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DVD
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Any problems / questions?
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Learning outcomes
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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
1)
2)
3)
4)
5)
6)
7)
8)
9)
10)
11)
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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Pharmacokinetics:considering
such terms as





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

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
oral
Parenteral
IV
sublingual
Topical
transdermal
Absorption
inhalation
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?v=xiuWdJYyI
Ks
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Absorption
Distribution
Metabolism
Factors affecting
Low albumin
Problems with:
Heart
Circulation
Diabetes
Bound drugs are pharmacologically inactive because the drugprotein 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

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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 it’s
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?

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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…
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http://www.youtube.com/watch?v=tnnoPedW
O7M
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…best to leave now if easily offended!
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Pharmacodynamics
“is
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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
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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/animat
ions/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
/ligand-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
/facilitated_diffusion.swf

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Enzyme inhibitors

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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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Chemotherapeutic agents

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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
Amino
acids
Class 3 reactions
Class 2 reactions
Class 1 reactions
Glucose
Precursor
molecules
Nucleotides
Proteins
RNA
DNA
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Physiological Variability
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Liver disease
Chronic alcoholism
Renal disease
Allergy
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Exam Style MCQs

a)
b)
c)
A receptor antagonist:
binds to a receptor and activates it
binds to a receptor without causing
activation
blocks an enzyme
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
a)
b)
c)
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:
a)
b)
c)
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:


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Receptor agonists
Receptor antagonists
Action at enzymes
Ion channels
Carrier molecules
Chemotherapy
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Short answer questions:
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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
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