Drugs And Receptors Flashcards
What are the two overarching mechnisms that drugs can use?
Blocking the action of an endogenous ligand, an angoist, or activate a receptor (antagonist)
What is the binding of drugs goverened by?
The laws of mass assoicaation, the drugs must have affinity for a receptor
What are the two things nesscary for the activation of a receptor?
Affinity and intrinsic efficacy
What are the features of anatgnoists?
Only have affinity, no efficacy
What is effiacy/
The ability of a drug to illicit a respone in a tissue, a combination of intriinisc efficacy and tissue dependant factors
How would you measure drug binding?
Using a radioactively labelled ligand to find Kd, o Pharmologically to determine Ka.
What is Kd?
Kd is the dissociation constant, which is where 50% of the receptors are occupied by drug, and is a measure of the affinity
What does a low value of Kd indicate?
A higher affinity for the drug
How would you demonstraate the functional measurable response of a drug?
Shown by concentration response or dose response curves
What is the difference between concentration and dose?
Concentrtion refers to when the drug is used agaisnt a single cell, whereas dose refers to when the drug is used on a entire animal
What is EC50?
The concentration of drug where you achieve 50% of the maximal response
What governs the value of EC50?
Affinity, intrinsic efficacy, and tissue dependant events, therefore the whole efficacy
What is EC50 a measure of?
Potentancy
What is Potency>
A combination of the affinity and efficacy of a drug
What are the different aspects of a drug?
Affinity and efficacy (and thereby potency) selectivity, drug metabolism, physicochemical affects.
What are the two common asthma drugs and the receptor tht they target?
Salbutamol and salmetral, and they target the B2 Adrenoreceptor which is involved in relaxation of the lungs.
What is the specificity of salbutamol to the B2 adrenreceptor?
It has a Kd of 20 um for B2 and 1um for B1, which is poor, however a low efficacy for B2 receptors makes it useful within treatment
What are is the specificity of salmetral to the B1 Adrenoreceptor?
It is 3455x more specific to B1, however, it has the same intrinsic efficacy on both receptors
Why is it important asthma drugs are specific to B1 adrenoreceptors?
As B2 adrenoreceptors are found on the heart and can increase heart rate, which can lead to angina.
What are the most common targets for drugs?
Proteins (enzymes in 47% of cases, or g protein coupled receptors)
How does receptor number influence potency?
A greater number of filled receptors generally increases potency of the drug, however, you may not need all of the receptors filled to achieve a maximal response.
Why would you have spare receptors on a tissue/
Increase sensitivity, allowing response at low amounts of angoist, and you can change the amount of receptors to alter the sensitivity to a drug
Describe one of the contributing factor in developing tolerance to drugs.
Tissues adapting by reducing the number of receptors, so that you cannot achieve the same maximal response
What is a partial agonist?
Some drugs can produce the full response even with the maximal receptor filling system, (they are often less good at inducing the active state of a receptor.)
What is the relationship between EC50 and Kd in a partial angoist?
EC50 is equal to Kd
What is the intrinsic activity of a partial angoist when compared with a full agnoist?
They have a lower intrinsic activity (often have the same efficacy))
What is the clinical relevance of partial agnoism?
They allowed a more controlled response to certain drugs, can be used in treating addiction to heronin (bueprnonmorphine)
How is bueprenanmorphine used in treating a heron in addiction?
Has a higher affitnity but lower efficacy that heronin,acts at the same u-opoid receptors if given instead or heronin at first can cause severe withdrawal symptoms due to the partial agonism, can be used to help enable gradual withdrawal
What are the three types of antagonism that drugs can perform?
Irreversible competitive antagonism, reversible competitive antagonism, and non competitive antagonism
What is the mechanism of irreversible competitive antagonism?
Relies on the equlibrumm between the receptor and the molecule, causes a parelle shifit to the right of the dose response curve and is surrmountable
What is a example of a drug that uses reversible competitive antagonism?
Naloxene, is. High affinity competitive anatagonist at the u-opioid receptor, and can be used to treat opioid overdose.
What is the mechanism of irreversible competitive antagonism?
Is where the antagnoism diffuses away slowly if at all, and causes a parallel shift to the right of the dose response curve, and at a higher concentration helps to suppress the maximal response.
Give two example of drugs that are irreversible competitive anatgnoists.
Plavix, used to treat thrombosis, and phenoxybenazmine, is a non selective irreversible adrenoblocker used to treat vascontriction in the production of excessive adrenaline by tumours of the adrenal cells.
What is the mechanism of non competitive antagonism?
Bind at allosteric sites, and have similar effects to irreversible competitive antagonism
What are examples of drugs that work by irreversible competitive antagonism?
Cinclet, and a maravian.
