1 introducing pharmacokinetics and pharmacodynamics janice davies pharmacist room 23 maudland...
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Introducing Pharmacokinetics and
Pharmacodynamics
Janice DaviesPharmacist
Room 23 Maudland [email protected]
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
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) Drug interactions
2) Duration of effect
3) Unwanted effects
4) Reduction in symptoms
5) Modification of disease progression
6) Accumulation on repeat dosage
7) Absorption from the site of administration
8) Elimination from the body
9) Delivery to the site of action
10) Effects at the site of action
11) Interaction with cellular component
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Pharmacokinetics:considering such terms as
Route Absorption Distribution Hepatic Metabolism Metabolic products Protein Binding Renal Excretion Half-life Toxicity
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Distribution
Metabolism
Excretion
Absorption
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Absorption
Route
EnteralParenteral
IVTopical
transdermal inhalationoral sublingual
Distribution
Systemic circulation
Absorption Absorption
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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
Absorption animation
http://www.youtube.com/watch?v=xiuWdJYyIKs
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Distribution
Factors affecting
Absorption Metabolism
Low albumin Problems with:Heart
CirculationDiabetes
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 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 mgs2nd dose 100mgs + 50 mgs still present = 150mgs3rd dose 100mgs + 75 mgs still present = 175mgs4th dose 100mgs + 88mgs still present = 188mgs5th dose 100mgs + 94mg still present = 194mgs6th dose 100mgs + 97mg still present = 197mg
As can be seen, accumulation becomes less ateach 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
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?v=tnnoPedWO7M
…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 wallLigand-gated ion channels, milliseconds e.g GABA benzodiazepines, Nicotinic AChhttp://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
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
Cytotoxic drugs act by interfering with cell growth and division at different stages of the cycle
Anti-infective drugs
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Cell wall
Cell membraneDNA
Bacterial Cell
Cla
ss 1
reactio
ns
Cla
ss 2 re
actio
ns
Cla
ss 3
reactio
ns
Glucose Precursor molecules
Amino acids
Nucleotides
ProteinsRNADNA
Metabolism of bacterial cell
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Physiological Variability
Liver disease Chronic alcoholism Renal disease Allergy
Exam Style MCQs
A receptor antagonist:
a) binds to a receptor and activates it
b) binds to a receptor without causing activation
c) blocks an enzyme
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The pharmacodynamics of salbutamol can be explained by its:
a) activity on enzymes
b) activity on ion channels
c) activity on receptors
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Warfarin has a:
a)Narrow Therapeutic Index
b)Wide therapeutic range
c)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
ORTrounce, 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