ICPP 6 Flashcards
Why is it important to consider drugs in molarity rather than concentrations?
Same concentrations of different compounds can be totsally different concentrations of molecules
What is intrinsic activity?
The ability for a ligand to activate a receptor
What governs the efficacy of a drug?
Intrinsic efficacy plus cell/tissue-dependent factors such as receptor number
What is Kd and what can it be used to show?
Dissociation constant, a measure of AFFINITY.
The amount of drug needed to occupy 50% of receptors
What does a low Kd indicate?
High affinity
What can you use to assess binding?
Radioligands
What is Ec50
Concentration of drug that gives 50% of maximal response
What does EC50 value indicate?
Potency - depends on both affinity and efficacy.
What shape is a concentration - response curve?
Sigmoidal
What are the properties of Salbutamol?
Selective efficacy for B2 receptors over B1 adrenoceptors, less selective affinity than salmeterol
What are the benefits of salmeterol?
It has much higher selective efficacy for the B2 receptor, but equal efficacy for both receptors.
insoluble so cannot be given IV
How can you tell if spare receptors are present?
If 100% binding gives 100% response then no spare receptors.
If <100% binding gives 100% response then must be spare receptors.
Why do spare receptors exist?
Amplification in signal transduction pathway, one receptor can cause a big response
Increase specificity - allow responses at low conc of ligand
Lower drug conc needed - fewer side effects
How does increasing receptor number alter specificity?
Increased receptors means increased specificity
how can partial agonists become full agonists?
Increase in receptor number
Give an example of a partial agonist
buprenorphine
What are the 3 types of antagonist?
- Competitive reversible
- Irreversible competitive
- Non-competitive (allosteric)
What is IC50?
The concentration of antagonist which inhibits 50% of the response.
How do competitive antagonists alter the % reponse?
Can still achieve maximal response but higher concentration of ligand required. Right shift.
Give an example of a competitive antagonist.
Naloxone at mu-opioid receptors to reverse respiratory depression
How does the agonist/response curve differ for irreversible antagonists?
After spare receptors have bound, 100% response cannot be achieved and begins to decrease.
Give an example of an irreversible antagonist and its therapeutic effect.
Phenoxybenzamine.
Tumour of chromaffin cells in adrenal medulla results in excessive adrenaline production. Phenoxybenzamine inhibits the alpha1-adrenoceptor no matter how much adrenaline is produced.
