Drug-Receptor interactions Flashcards
Define a drug
A chemical substance of known structure. not including food, that when administered produces a biological effect
Why do drugs show side effects and toxicity
- Drugs are insufficiently selective
2.Drugs may be very selective but target site may underlie many processes across the whole body leading to off target/side effects and toxicity
3.Use of the drug across a long time period can cause permanent changes in structure and function
4.Not knowing enough about the disease and how it works
5.Patient variability
6.drugs interacting with each other
State how drugs can be administered (10 ways)
I PUT A QUESTION ON PADLET FOR CONIBEAR CHECK IF ANSWER
CHECK IF JOHAN ANSWERED QUESTION ON G PROTEINS
Why is it important to use the generic name of a drug and not the brand
The generic name gives information about the site of action. brand names tell nothing e.g. statins like simvastatin and fluvastatin (lower levels of LDLs in blood) end in the word statin telling you they are statins, beta blockers (inhibit beta adrenoreceptors) also end in “lol” normally
Why are drugs taken (5)
- To produce a cure - antibiotics
- To suppress symptoms - anti allergy
3.To prevent a disease or symptom - Aspirin
4.Diagnose a disease - neostigmine - recreational
Define an agonist
A drug that evokes a response when combined with a receptor.
Define an antagonist
A drug that prevents the action of another drug, transmitter or naturally occurring hormone
Explain the difference between agonist and antagonist
An agonist binds to a receptor to active the receptor while antagonist bind to receptor and do not activate it instead they occupy the site to prevent it from being activated
Agonists have efficacy antagonists do not
What is the law of mass action equation and what does it define
It defines the relationship between the quantity/ concentration of free drug and the number of drug receptor target.
rate of reaction is proportional to the concentration of the reactants
Equation for the concentration of drug receptor complexes
And the equation for rate of dissociation and rate of association
[D] + [R] (reversible reaction arrow) [DR]
Rate of association = k+1[D][R]
(the +1 is subscript)
rate of dissociation = k-1[DR]
(the -1 is subscript)
What is the relationship between the rate of association and dissociation at equilibrium
equal
Explain the term Kd(subscript) what its used for and what it means
The binding of a drug to a receptor is governed by affinity. higher affinity = stringer binding. Kd(subscript) quantifies affinity
Kd(subscript) = [D][R]/[DR]
units of Kd(subscript) are molar
the value is Kd(subscript) is the concentration of drug that drug that occupies 50% of the receptors
lower the Kd(subscript) = higher affinity
Describe the measure used to quantify drug binding
Drug binding is quantified by determining the Kd(subscript) value.
Kd(subscript) is the concentration of drug that occupies 50% of the binding sites
it is the measure of affinity and a constant
What are the conditions needed for the receptor occupancy equation to be valid.
- Equilibrium
2.1drug molecule binds to one receptor molecule - Drug concentration at recpetor same as that applied to system
- A negligible amount of drug added is bound
- the binding of one drug molecule does not effect the binding of another
What is does the shape of the curve look like when drug concentration (x) and fractional occupancy (y)
a smooth curve with an asymptote which represents total number of receptors.
A large increase in fractional occupancy with a small increase in drug concentration at the beginning.
conclusions
1. receptor occupation increases with drug concentration
2.binding is saturable
What is a semi-log plot and why is it normally used instead of a linear plot
It means using log([DRUG]) instead of [DRUG]
changes the rectangular hyperbola shape into a sigmoidal shape.
allows us to see the threshold of binding easier
gives a better definition of the maximum
What are the units of Kd(subscript)
Molar
What’s the relationship between the affinity of a drug and the position of the binding curve on the axis (concentration fractional occupancy graph)
The higher the affinity the lower the Kd(subscript) value and the binding curve is more to the left of the graph
leftmost curve has the highest Kd(subscript)
What does an agonists ability to produce a pharmacological effect depend on
- the binding of the drug to the receptor (affinity).
2.activation of receptors and production of response(efficacy).
define efficacy
The rate at which an agonist activates the DR complex
[DR]⇌[DR*]
rate of forward reaction = alpha
rate of back ward reaction = beta
Describe full and partial agonist
A full agonist is where the bound agonist resides is the active DR complex for most of the time and is capable of evoking a maximum response. high efficacy
partial agonist is where the agonist resides in the inactive DR complex most of the time and cannot evoke a mix response. low efficacy
A partial agonist must bind to all the receptors to produce its max response, the max response is less than the full response that the tissue is capable of.
Still have therapeutic value
What is the name of the shape of the curve in a concentration response graph when its a linear plot
Rectangular hyperbola
What is the name of the shape of the curve in a concentration response graph when its a Semi-log plot
sigmoidal
this uses log of concentration instead if concentration
it condenses the rate of concentrations
What is EC50
the concentration of drug that produces 50% of the max response - this quantifies the potency of an agonist
When functional response and binding curves are plotted on the same graph what determines the separation between the curves and what does it show
efficacy - greater efficacy = greater distance between them
it shows that there is not a 1 to 1 relationship between response and occupancy. this gives rise to spare receptors
What does the proportion of receptors in the receptor reserve depend on
Efficacy and number of receptors
What is potency
How much of a drug is needed to produce a particular response.
higher potency = less drug concentration
lower potency = greater drug concentration
What are the components of a biological response
Affinity, efficacy, receptor number
Name a therapeutic use of partial agonists and how.
Salbutamol (asthma thing)
During an asthma attack there is a contraction in the bronchi smooth muscle, this muscle relaxes by activation of b2 adrenergic receptors
adrenaline can activated these receptors as well as b1 and b2 receptors on the heart this causes and increase of heart rate and force of contraction. therefore adrenaline would relax the bronchi smooth muscles but would put the patient at serious risk of heart attack. Salbutamol is a selective b2 adrenoreceptor agonist, but a partial agonist. the magnitude of efficacy of a partial agonist is dependant on receptor number. bronchi muscles have a large number of b2 receptors where as the heart has very few. causing a significant response in the bronchi muscles but not the heart.
What are the different types of antagonism and how do they work
Competitive - binds to the antagonist recognition site preventing the agonist from binding
Non-competitive - does not bind to the agonist site but prevents the agonist from binding in another way
Uncompetitive - when the antagonist binds to the activated receptor
physiological - when a neurotransmitter/ hormone is countered by the action of another neurotransmitter/hormone
Antagonism may be reversible or irreversible
How can reversible competitive antagonism be overcome
It can be overcome by increasing the concentration of agonist
What is Kb and what does it represent and units
The equilibrium constant for the antagonist
units are molar
the lower the concentration of kb the better the reversible competitive antagonist is.
What is the Gaddum-schild equation
[D1]/[D1]’ = 1+ [B]/[kb]
B = antagonist
