Lecture 2 Flashcards
What is the affinity constant (Kd) and what does it tell us about the affinity of the drug to the receptors? What is Bmax?
Kd is the concentration (L) of the drug, at which half the receptors have been bound to by the drug. Thus, the lower the value of Kd, the higher the affinity of the drug, because they are strongly attracted to each other.
Bmax is the concentration at which all the drug sites have been occupied.
i.e. The higher the affinity of the receptor, the lower the drug concentration required to achieve a given level of receptor occupancy.
Does affinity correlate with biological response?
No. Receptor occupancy and response is not strictly proportional. You may only need a small amount of receptor occupancy to produce a maximal response, many factors downstream of the receptor binding interact to produce a response.
I.e. affinity
What is efficacy and what are the 3 targets?
the ability of a drug to bind to a receptor and change its action, and it is measured by Emax.
Agonist - positive efficacy - promote cellular response
Antagonist - no efficacy
Reverse agonist - negative efficacy - decrease the cell’s basal cell activity.
What is the maximum response of a drug determined by?
Efficacy and tissue properties - a drug may be a partial agonist in one tissue and a full agonist in another.
Draw the effect of reversible competition on the agonist response curve and explain it.
Shift to the right - harder for the agonist to produce the effect.
Draw the effect of an irreversible competition on the agonist response and explain it.
Curve - same start but the max is lower. This involves covalent bonding to the receptor. It reduces number of binding sites for the agonist.
What is the spare receptor theory?
At lower concentrations of an irreversible antagonist you may still get maximum effect, because you don’t need the agonist to bind to every receptor to produce the effect. This is why at small doses an irreversible antagonist looks like a reversible one. You require higher concentrations of agonist at these lower doses because it becomes harder to find a receptor.
In contrast to drugs that can act on receptors which can activate or inactivate, most drugs acting on enzymes or transporters only inhibit - why is this?
Most conditions revolve around the loss of neurotransmitters, if you activate these then you are likely to break the neurotransmitters down and remove them from the synapse.
What are non-competitive antagonists?
Look at book.
How do you inactivate acetylcholine?
Inactivation involves inactivating the enzyme acetylcholinesterase, which is found in the synaptic cleft, on the post-synaptic membrane. It breaks down acetyl choline into acetate and choline.
What are the 2 classes of acetylcholine esterase inhibitors? give an example for each class.
Irreversible AchE inhibitors are highly toxic, examples are nerve gases.
They form incredibly stable phosphate bonds with AChE - resist hydrolytic cleavage for hours.
Reversible AchE inhibitors - used in disorders characterised by a decrease in cholinergic function. It increase the time each molecule remains in the synapses one molecule can activate more than one receptor.
Used in myasthenia gravis - e.g. Mestinon
Used in the treatment of Alzheimer’s disease - Donepezil
How is the inactivation of serotonin reduced?
It is reduced by Selective Serotonin Reuptake Inhibitors. An example is prozap.
Do the revision question - with a group too.
Do the revision question - with a group too.
