Pharmacology 2 Flashcards
Briefly - how do drugs act as a ligand for receptors
- they recognize a transmitter or hormone
- they trigger a cellular response
Briefly - how do drugs act as Endogenous ligand
neurotransmitter of hormone or other mediator
Which is the most common receptor drug target
GPCRs (receptors coupled to G proteins)
5 receptors targetted by drugs
- nuclear receptors
- Catalytic receptors e.g. receptor tyrosine kinases
- cytokine receptors
- ligand-gated ion channels
- Receptors coupled to G proteins (GPCR)
Examples of other type of drugs tnat don’t act on receptors
- Cyclo-oxygenases (NSAIDS)
- Voltage-gated ion channels (local anaesthetics)
- Precursor synthesis (L-DOPA)
- 5-HT transporter (fluoxetine (Prozac))
What tend to be receptor mediated actions? (4 things)
- of high potency/affinity
- Tissue selective
- Chemically-specific
- inhibited by specific antagonists (assuming drug is agonist)
How can we calculate the effect of a drug
% of receptors occupied (linear correlation for now)
How to calculate dissociation constant
how can you calculate what proportion of receptors are occupied by a drug
Proportion of Receptors occupied by Drug p = [D] / (kD + [D])
You can figure this out even if you don’t know how much receptor is around…
What does reflects the kD
Reflects the affinity of a drug for its receptor
What does it mean when [D] = kD
50% of receptors are occupied
hence, what does a low kD mean
high affinity, and vice versa
what is an agonist drug
mimics actions of the endogenous ligand
what is an antagonist drug
counters the actions of an agonist
What is the EC50
The concentration of a drug that is needed to reach 50% of the maximal effect
whta is the theory behind spare receptor
The maximum effect of a drug would be achieve with less than 100% receptor occupancy by the agonist drug
What does a spare receptor theory means for the drug effect?
The maximum effect and EC50 will be achieve at a lower concentration than the regular curve
difference in efficacy between full agonist, partial agonist and antagonist
Full agonist: high efficacy
Partial agonist: medium efficacy
antagonist: zero efficacy
how can partial agonist block the effect of a full agonist?
They both act at the same receptors, so some are occupied by partia and some by full agonist - the effect is then less then 100% (considering that the full agonist alone would have 100% effect)
What is the basal activity
The activity that receptors do by themselves, without the drug. independent of agonist/ligand
What would be an inverse agonist
It has a negative efficacy, it depresses the basal activity of the receptors
What specific condition is required for inverse agonist to have an effect
it only applies where unbound receptors produce a detectable basal signal
Efficacy vs potenxy
Efficacy: How well an agonist stimulates a certain effect
- 2 agonists could have the same efficacy, but they might do so in different concentration range
Potency: concentration range at which an agonist achieve the max effect
comment on efficacy and potency
- C is less efficient than B
- C is more potent than B
What is a surmountable antagonist
a competitive antagonist that will bind with receptors, but an increase in the agonist concentration could still reach a maximum efficacy (the agonist can replace the antagonist when you increase the agonist concentration)
What is an insurmountable antagonist
it is a competitive irreversible antagonism - meaning that agonist can’t compete when the antagonist is occupying a receptor
