Flashcards in Pharmacodynamics Deck (53):
Do most drugs bind reversibly or irreversibly to receptors?
How is drug concentration measured?
What is intrinsic efficacy?
Ability of a drug to activate a receptor
What is efficacy?
Ability of a ligand to cause a response
What do agonists and antagonists have in reference to efficacy, affinity and intrinsic efficacy?
Agonists - have affinity, intrinsic efficacy and efficacy
Antagonists - have affinity, NO intrinsic efficacy/efficacy
How can drug-receptor interactions and binding affinity be measured? What sort of graph can be plotted?
Using a radioligand - radioactively labelled ligand
Graph plotted of [drug] against proportion of bound receptors
Gives a hyperbolic curve
What is Bmax?
Maximum binding capacity (number of receptors)
A high Kd = _________ affinity
What is Kd?
Ligand concentration that occupies 50% of the available receptors (1/2 Bmax)
Drug concentration is usually measured using which type of scale? Therefore graphs with [drug] on one axis usually give which shape curve?
How can you measure drug efficacy?
With a concentration-response curve
What does a concentration-response curve measure?
% response vs. [drug]
What is Emax?
100% drug response (maximal drug response)
What is EC50?
Effective [drug] giving 50% of the maximal response
What is concentration (of a drug)?
Known concentration of a drug at the site of action
What is dose?
Unknown concentration of drug at site of action (what you give to the patient)
EC50 gives an indication of _______/________
Efficacy and potency of a drug
What is potency?
Generation of a measurable response
What is required for a ligand to have potency? (3)
Things to happen to cause a response
Giving drugs for asthma is an example of functional antagonism. What is meant by this?
Drugs for asthma cause relaxation of smooth muscle rather than just preventing contraction of smooth muscle
Drugs for asthma act on which receptors?
Activation of B1-adrenoceptors results in what?
Increased heart rate/force of contraction of the heart
What two drugs work on B2-adrenoceptors for the treatment of asthma?
What selectivity and selective efficacy does salbutamol show to b2-adrenoceptors?
Has poor selectivity for b2-adrenoceptors - so similar affinity
Has good selective efficacy for b2-adrenoceptors - causes a greater response in b2-adrenoceptors)
What selectivity and selective efficacy does salmeterol show to b2-adrenoceptors?
Has good selectivity for B2-adrenoceptors
No selective efficacy between the receptors
How does salmeterol work compared to salbutamol?
Salmeterol is longer lasting
Why are there problems in prescribing salmeterol and salbutamol to patients with cardiac problems?
Salmeterol = insoluble
Salbutamol = will cause increased heart rate/contraction
You would expect a 50% binding to result in 50% response but this is not the case, why? What does this result in?
There is only so much a muscle can contract and so much a gland can secrete
It means there will be some spare receptors that do not contribute to a response
What are spare receptors?
Receptors that don't contribute to a response
If a situation existed where there were spare receptors, what would the binding curve look like compared to the response curve?
Response curve shifted to the left compared to the binding curve
Where are spare receptors often found?
When receptors are catalytically active e.g. GPCRs
What is the benefit of having spare receptors?
Allows increased sensitivity
E.g. A response at a low [agonist]
Changing receptor numbers changes agonist _____
Are receptor numbers fixed?
What can cause an increase or decrease in receptor numbers? What can this result in, in reference to drugs?
Increase when there is low activity
Decreases when there is high activity
What is a full agonist? Are there spare receptors found in a full agonist?
Can give a full, maximal response
Has spare receptors
What is a partial agonist? Does it have spare receptors?
Does not give a full response - low intrinsic efficacy
No spare receptors
What is the benefit of using partial agonists as drugs?
They allow a more controlled response
How can heroin cause death?
Can result in respiratory depression ---> death
What is buprenorphine?
A high affinity partial agonist - used to gradually withdraw use of illicit opioids
How can a change in the number of receptors affect the action of a partial agonist?
It could change a partial agonist into a full agonist
What is the efficacy of a partial agonist compared to a full agonist?
Partial agonist has a lower efficacy
What do antagonists do?
Block the action of agonists - bind and do not cause a response
What are 3 types of antagonism?
Reversible competitive antagonism
Irreversible competitive antagonism
Non-competitive antagonism (allosteric)
What is IC50?
The [antagonist] giving 50% inhibition
What does IC50 give an indication of?
What happens in reversible competitive antagonism? How can this inhibition be surmounted?
Antagonist competes with the agonists for binding
By increased agonist concentration
What result does reversible competitive inhibition have on the % response-concentration curve?
Shift to the right
What happens in irreversible competitive antagonism?
Antagonist dissociates from receptor very slowly/not at all
Usually as a result of covalent modification/very high affinity
Is irreversible competitive antagonism surmountable by increasing [agonist]?
What effect does irreversible competitive antagonism have on the % response - concentration curve?
Shifts it to the right and can lower the maximal response at high [antagonist] as there are not enough receptors
What is the site where ligands bind called?
The orthosteric site