Drug Receptor Interactions Flashcards
What is a pharmacological antagonist
Pharmacological antagonist binds to the same receptor as the agonist does. It occupies the binding site of the receptor and prevents the binding of agonist to the receptor. In this way, it prevents the activation of the receptor.
Define affinity and efficacy of a drug
Affinity-The drug’s ability to bind to a receptor
Efficacy- ability of a drug to change the receptor it is bound to in a way that will cause the receptor to produce an effect
Agonist drugs have both affinity and efficacy true or false
True
Name the types of agonists and explain how they work
Full agonist-an agonist that produces maximal effect
Partial agonist-an agonist that does not achieve maximal effect
Can act as an antagonist in the presence of a full agonist. It reduces the effect of the full antagonist
Name two differences between full and partial agonists
Full-has high efficacy
May need to occupy only a fraction of receptors to produce a maximal effect
Partial- low efficacy as compared to that of the full agonist
Needs to occupy all receptors to produce a maximal effect
It can act as a partial antagonist
What are inverse agonists
Agonists that bound to the receptor to produce an opposite effect of an agonists
They are not antagonists
Occurs in situations where the receptors show constitutive/intrinsic/basal activity.
•They act by silencing constitutively active receptors.
Define potency of agonists
Amount of a drug needed to produce a given effect
●Determined mainly by the affinity of the receptor for the drug
A small amount of drug is needed to produce an effect then that drug is said to
Be more potent
Define ED50
The amount of drug needed to produce a median response
It is a measure of agonist potency
Define relative potency
Only a relevant comparison when drugs all have the same mechanism of action and produce the same effect (of any magnitude)
It is the ED50 or one drug divided by the ED50 of another drug
To find the relative effficacy what do you do?
Find the ratio between the efficacy of one drug and the other drug
Two drugs can have the same efficacy but not the same potency and can have the same potency but not the same efficacy. True or false
True
What does the slope of a drug response curve represent
Indicator of useful dosage range (steepness of the curve)
Name four importance’s of dose response curves
Determining if a drug produces a certain desired effect
●Determining potency or dose required in producing effect
●Comparing one drug with others:
●Efficacy
Define therapeutic index
●A quantitative measure of the relative safety of a drug
Therapeutic Index =
TD50 or LD50 divided by ED50
A larger value of TI is more desirable
Name two parameters that can be used to find relative safety
Therapeutic index and LD50 being more than ED50
Therapeutic window
Dosage range which produces therapeutic effect without causing adverse effects
●A measure of the lack of overlap between DRCs of therapeutic and toxic/lethal effects.
Efficacy is valued over potency
True or false
True
The smaller the amount of drug needed to produce the max response , the more potent the drug is true or false
True
The bigger the -log of EC50 the more potent the drug is true or false
True
How do you find the median in order to find the median response
Find the threshold response and the max response then find the median number
Example- threshold is 20 and max is 100 so arrange the numbers in ascending order then find the middle number
The higher the LD50 the safer the drug why
Cuz a higher dose of the drug is needed to kill the organism so even if there is a mistake and there’s a miscalculation the patient won’t die
Example if drug dose for it to be effective is 20 then LD50 should be 50 or 100 so if there’s a mistake and the person gives 30 instead of 20, the patient won’t die
Antagonist drugs are have efficacy not affinity true or false
False
They have affinity and not
Efficacy
Types of antagonist drugs and explain
Competitive -if antagonist and agonist are competing for the same receptor
non competitive -there is no competition and the receptor isn’t stimulated or there’s no effect no matter how much agonist is added
Name and explain the branches of competitive antagonist drugs
Irreversible-All the receptors that have been bound by the antagonist and can’t be bound the agonist so the agonist bounds to spare receptors ( in this case a full agonist is what we’re talking about)
As the dose of the antagonist is increased the response of the agonist reduces cuz more of the antagonist displaces the agonists that have been bound
May see initial parallel shift if spare receptors are present in the tissue
Occurs with drugs that posses reactive groups which form covalent bonds with receptor (aspirin, omeprazole, MAO inhibitors etc.)
Reversible-agonist can replace the antagonist even if the antagonist forms a reversible bond with the receptor at the binding site if there are enough agonists to overcome the antagonist
The most common type of antagonist
The agonist and antagonist form only short-lasting combinations with the receptor, so
The equilibrium between agonist, antagonist, and receptors can be reached during the presence of the agonist true or false
True
Name some characteristics of reversible antagonist
the action of the antagonist can be overcome by a sufficient increase in the concentration of agonist (i.e., the antagonism is surmountable).
●in the presence of the antagonist, the agonist log concentration-effect curve is shifted to the right without change in slope or maximum. (Rightward shift means a high concentration of the agonist is needed to achieve the max response cuz the agonist is being blocked by the antagonist
●the extent of the shift being a measure of the dose ratio(concentration ratio).
●the dose ratio (magnitude of the shift) increases linearly with antagonist concentration (i.e. obeys Schild equation).
In the presence of the antagonist more of the agonist is needed to achieve a maximum response true or false
True
Effect of the antagonist is seen when the agonist is introduced true or false
True
How do you measure the potency of an antagonist
Measured when the agonist is used in the presence of the antagonist . The way the antagonist is able to affect the agonist will show how potent the antagonist is
pA2- concentration of the antagonist that’ll reduce the agonist response by half
concentration required to produce a certain degree of rightward shift
●negative logarithm of the molar concentration of antagonist which increases the concentration ratio (or EC50) by 2 fold
As the antagonist is increased the curve shifts even more. The higher the pA2 the
More
Potent the antagonist
p- negative log of something
Define pAx
Measures extent of shift of CRC
•defined as the factor by which the agonist concentration must be increased to restore a given response in the presence of the antagonist
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How does non competitive antagonism work
It works in two ways
Either the antagonist has a different site to bind to to stop the agonist from working so there’s no competition. They both bind at different sites on the receptor and where the antagonist is too stops the agonist from working
Or the antagonist comes into the cell to block the downstream mechanism to stop the agonist from working even after it has bound to the receptor
In non competitive antagonism the slope and max response change why
The antagonist is stopping the agonist from working The effect of a non-competitive antagonist on the DRC for an agonist would be the same as the effect of an irreversible antagoni
Define chemical antagonism
Agonist and antagonist form inactive complex in solution. Example:
•Heparin & protamine sulphate
Antacid - acid is the agonist in the body and base is the antagonist in the liver salt to cause a neutralization reaction
Physiological antagonism
Interaction of two drugs whose opposing action in the body tend to cancel each other
Example: when drug A increases bp and drug b decreases bp and they’re taken together those effects cancel each other out
Define desensitization, tachyphylaxis, tolerance and refractoriness
D- receptors get used to the concentration of the drug so it’s effect gradually reduces leading to more of the drug being needed
Ta- desensitization occurs faster
To- desensitization occurs slower.describes a more gradual decrease in responsiveness to a drug
Refractoriness- no response at all when drug is taken or loss of therapeutic efficacy
Define drug resistance and down regulation
Drug resistance
●loss of effectiveness of antimicrobial or antitumour drugs
●Down-regulation
●Reduction in response due to a decrease in the number of receptor
Reduction of receptor number (density) following continued exposure to a ligand which has affinity for the binding site involved
●can involve decreased receptor affinity, but this is less common
Characteristics of desensitization
Specific
●involves effects at the level of the receptor
●involves only agonists acting at that receptor
●Non-specific
●involves effects distal to the receptor site
●involves all agonists whose receptors share a common receptor-effector coupling pathway
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●Acute
●develops rapidly -usually rapidly reversible loss of receptor function
●may involve receptor interzalisation without destruction of receptors
●Chronic
●develops slowly - less readily reversible
●often accompanied by true receptor loss
●may involve interna
Imports of desensitization
protective mechanism/s
•internalisation: possible signaling functions
•disease states may be linked to congenital or acquired receptor malfunction - e.g. myasthenia gravis
•receptor desensitization can be induced deliberately: e.g. Rx of prostatic cancer
Name five unusual responses to drugs
Idiosyncratic response - unusual response
●Hyporeactive - less than normal response
●Hyperreactive - more than normal response
●Hypersensitivity - allergic or other immunological reaction
●Tolerance - decreased response with continued administration
Tachyphylaxis- rapidly developing tolerance
What kind of receptor has its Effects exerted mainly at the level of gene transcription
22 and regulate growth
•They are thus important targets in regulating excessive growth
Enzyme linked receptors
They mediate the actions of many protein mediators, e.g. growth factors & cytokines, and hormones e.g. insulin & leptin
Which receptor does this?
Enzyme linked receptors
Amoxicillin is the generic name for Amoxil
True or false
True
