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29 Cards in this Set
- Front
- Back
How are drug effects quantified? |
Drug effects are “quantified” by studying the relationshipbetween drug concentration (or dose) and the responseproduced by the drug. This relationship is described byconcentration-response curves |
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What do the concentration and log concentration graphs look like? |
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What is the response measured to a drug determined by? |
The effect of a given drugcan be measured in manydifferent ways • The response measured isdetermined by the type ofexperiment being performed |
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What are the main types of pharmacological experiement? |
There are three main typesof pharmacologicalexperiment • experiments in vitro • experiments in vivo • experiments ex vivo |
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What are experiments in vitro? |
Drug effects are studied ona piece of tissue dissectedfrom an animal (or human),and kept alive outside thebody. |
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Is in vitro the most common type of experiment? |
By far the most common typeof experiment, and includeexperiments on cells grown intissue culture |
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What responses might be measured? |
Responses that might bemeasured include changes inthe tension of a muscle,changes in the activity of anenzyme or changes in thesecretion of a hormone orneurotransmitter……….. |
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What happens in in vivo experiments? |
• Drug effects are studied inthe living animal (or human) • Include clinical trials • Tightly regulated by theHome Office • Responses that might bemeasured include increase inblood pressure; reduction inpain threshold; reduction inallergen-inducedbronchoconstriction…… |
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What are experiments ex vivo? |
• A tissue or organ is removedfrom an animal that has beentreated with a drug, and theeffects that drug has had onorgan function are tested invitro • Again tightly regulated bythe Home Office • Examples might includeexperiments to see whetherlong-term treatment with adrug induces liver damage oralters some aspect of brainbiochemistry |
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For experiments in vitro, what are the concentrations expressed as? |
• For experiments in vitro,concentrations are expressedin Moles per litre i.e. Molar(M) • 1 Mole of a drug contains 6.02x 1023 drug molecules andweighs the molecular mass, ingrams • A 1 Molar solution contains 1Mole of a drug dissolved in 1litre of solvent • Most importantly, a 1 Molarsolution of drug “X” willcontain the same number ofdrug molecules as a 1 Molarsolution of drug “Y” |
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What concentrations do most clinically useful drugs act at? |
Most drugs act at concentrations in the range 1 x 10-6M to 1 x10-12M ie they are very potent (see later) • Bare in mind however that a 10-9 M solution of drug stillcontains 6.02 x 1014 or 602000000000000 drug molecules perlitre! • Often pharmacologists will use the prefixes milli (m)- micro (µ)- and nano (n)- for 10-3 ,10-6, and 10-9 respectively • Thus a 1 micromolar (µM) solution is the same as a 1 x 10-6 Msolution |
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Why is it not possible to use molar concentrations for experiments in vivo? |
It is not possible to use molar concentrations forexperiments in vivo, simply because the volume of thesolvent (eg blood) is not known |
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What are drug doses for experiments in vivo expressed as? |
Drug doses in this type of experiment are expressedas weight of drug per weight of animal eg 1 mg per kg(1 mgkg-1) |
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What does this allow? |
This allows an approximate extrapolation of the dosefrom, for example, a 20 gram mouse to a 70 kg human |
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What is the maximal effect, Emax? |
Indicates the maximumresponse a drug canproduce, i.e. the “top” ofthe concentrationresponsecurve.Increasing theconcentration of the drugproduces no greatereffect. |
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What are the Emax and EC50 on a concentration response curve? |
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What is the EC50? |
• Indicates the position ofthe curve on theconcentration axis • Defined as “the Molarconcentration of a drugthat produces 50% of themaximum response for thatdrug”. • Sometimes use otherpercentage values eg EC90or EC20 |
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What does potency mean? |
A vague but commonly used term, used to describethe concentration at which a drug is effective |
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When is a potent drug effective? |
A potent drug is effective in very small amounts |
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What is potency quantified by? |
Often quantified using the EC50 • Remember that the lower the EC50 the more potentthe drug |
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What does comparing two EC50 values allow you to do? |
Comparing EC50 values for two drugs with the sameaction allows us to calculate their relative potencies,described by the potency ratio (M) |
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How is the potency ratio calculated? |
• Drug ‘A’ is clearly morepotent than drug ‘B’. Youneed 20 times more of ‘B’ toachieve the same effect M = EC50(test)/EC50(standard) orLog M = logEC50(test) –logEC50(standard) |
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What is a bioassay? |
Determining the relative potency of different drugsis a key role of the pharmacologist • A “bioassay” is any techniques where the potency of adrug is determined by measuring the biologicalresponse it produces |
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What different bioassay have been developed? |
Pharmacologists have developed hundreds ofdifferent bioassays, ranging from cells in culture toclinical trials in humans to look at different aspectsif drug response • Bioassays underpin the development of new drugs inthe pharmaceutical industry |
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What is a 2+2 bioassay? |
• The simplest bioassay fordetermining the relativepotency of two drugs • Makes use of the fact thatthe middle portion of thelog concentration- responsecurves are almost linear,and if the two drugs areacting by the samemechanism, then the linesshould be parallel • ‘M’ can be obtained bycomparing two doses ofstandard (S1, S2) with twodoses of unknown (U1, U2) |
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What is the therapeutic index? |
The ratio between the toxic dose of a drug and thedose producing the desired therapeutic effect |
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What does the higher the therapeutic index mean? |
The higher the therapeutic index the less chance ofthe drug producing toxic side-effects in therapeuticuse |
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How is Therapeutic index defined? |
An important concept, but actually very difficult toquantify. Sometimes defined asTherapeutic index = LD50/ED50 LD50 = lethal dose in 50% of population ED50 = Effective dose in 50% of the population |
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Why is the theraeutic index no longer used? |
• Pretty meaningless definition from a clinicalperspective. Death is a rather extreme side effect! • In humans, Therapeutic index = TD50 /ED50 where TD50is the “toxic” dose in 50% of the population • Wide person to person variation in the both toxic andbeneficial effects of drugs • A drug can have different ED50’s depending on thedisease being treated eg aspirin against headache orarthritis • Ethically no longer defensible to obtain LD50 values inanimals. |