PHARM - Drug Targets and Action - Week 2 Flashcards
Define volume of distribution, and what it is not an indication of?
Indication of extent of distribution, but not location.
What is a composite of colume of distribution and clearance?
Half life, the time to stady state and dose interval
What four factors affect the concentration of of a drug in blood.
Absorption
Distribution
Metabolism
Excretion
Define pharmacokinetics.
Effects of the body on a drug
Define pharmacodynamics.
Effects of a drug on the body
Define an agonist.
A molecule that fits into a receptor to activate it.
Define an antagonist.
A molecule thats fits into a receptor to block its action.
Define an ion channel blocker.
A molecule that prevents permeation through the channel by blocking it.
Define an ion channel modulator.
A molecule that increases or decreases an ion channel’s permeation.
Define an enzyme inhibitor.
A molecule that fits into an enzyme to inhibit its normal reaction.
Define an enzyme false substrate.
A molecule that fits into an enzyme to result in an abnormal metabolite.
Define a prodrug.
A drug that once catalysed by a specific enzyme, will result in an active drug as the product/metabolite.
Outline the interaction between a false substrate and a transporter channel.
It results in the accumulation of an abnormal compound.
Define affinity.
A quantifiable measure of the molecular attraction to a receptor.
Describe the equation for the law of mass action.
[D] + [R] –(k+1)–> [DR] and
[D] + [R]
Define Kd, and what it represents.
It is the dissociation constant, the concentration at which 50% of receptors are bound.
What does a low Kd represent in terms of affinity?
A low Kd indicates a high affinity for the receptor.
What is the main factor that affects the effect of a drug?
The dose
How do receptors make drugs powerful and potent?
The amplification mechanisms through 2nd messengers.
Describe the following processes in both their mechanisms and in terms of how quickly they signal (in order from quickest to slowest): Kinase-linked receptors G protein-coupled receptors Nuclear receptors Ligand-gated ion channels
Ligand-gated ion channels - millisecond timescale
-Involves the movement of ions across a channel, leading to hyper- or depolarisation.
G protein-coupled receptors - second timescale
-Involves the amplification of a signal through signal trunsduction and second messengers.
Kinase-linked receptors - hour timescale
-Involves the phosphorylation of a protein factor, which will eventually result in gene transcription and protein synthesis.
Nucleus receptors - hour timescale
-Involves the drug entering the nucleus via a nuclear pore, and inducing gene transcription.
Consider a concentration-response curve. Describe its shape, and define the axes, what 50% on the y-axis represents, what the upper and lower limits of the graph mean.
It is a sigmoidal curve, with response as the y-axis, and Log concentration as the x-axis.
pEC50 represents the 50% mark on the response axis.
The upper limit represents Emax, and the drug is an agonist.
The lower limit of the graph represents an antagonistic drug.
Define the following:
Emax
EC50
Emax is a measure of the efficacy of a drug, and is represented by the upper limit of a concentration-response curve.
EC50 is a measure of the potency of a drug, how much drug is needed, and is represented by the 50% mark on the response axis of a concentration-response curve.
Can antagonists elicit a response in the body?
Yes, the effect is observed when an agonist is present.
Do antagonists have efficacy in vitro? What about in vivo, and what is this called?
They do not in vitro, but in vivo they do, and this is called clinical efficacy.
Describe how both an agonist and antagonist interact with a receptor, and what kind of efficacy applies to both.
Both drugs will bind the receptor, but only agonists will elicit a cellular response.
Agonists have intrinsic efficacy, while antagonists have clinical efficacy.
Consider an antagonist’s clinical efficacy. Is a bigger response generally always better? Explain.
No, you need to optimise the benefit (clinical efficacy), while minimising the risk (clinical toxicity).
True or false
All drugs have more than one action.
True
Describe the minimum effective, and maximum tolerated dose, and where the therapeutic window fits in.
Bearing your response in mind, how does this fit into a situation where a drug has two different therapeutic and toxic mechanisms? Name a consequence of this.
The minimum effective dose is the dose at which an effect first begins.
The maximum tolerated dose maximum dose delivered that does not cause death.
Between these two doses is the therapeutic window.
As all drugs have more than one action, unwanted side effects will constrain the usable dose of a drug.
What factors of a drug does pharmacodynamics deal with (4)?
Where it goes - affinity and selectivity
How much is needed - its potency and efficacy
What factors of a drug does pharmacokinetics deal with (6)?
How much is needed - its potency and efficacy How often it is needed (dictated by) -Absorption -Distribution -Metabolism -Excretion
Consider an antagonist’s clinical efficacy. Is a bigger response generally always better? Explain.
No, you need to optimise the benefit (clinical efficacy), while minimising the risk (clinical toxicity).
True or false
All drugs have more than one action.
True
In a sick patient, what 3 factors will the drug action depend on?
Target distribution/function
-pathophysiology
Organ system response
-reflexes
Idiosyncrasy
-genetics
