How do Drugs Work Through Receptors Flashcards
What determines drug binding?
Shape and attractive force
What is receptor occupancy?
KA is a measure of affinity
What is drug efficacy? How does it differ from affinity and potency?
Efficacy refer to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the potency of the drug and which is proportional to both efficacy and affinity.
What is potency? What are the factors that determine it?
Potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity.
A highly potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations.
The following factors lead to high potency:
- High Affinity
- High Intrinsic Efficacy
- Efficient S-R coupling - tissue-dependent
- Lots of Receptor - tissue-dependent
What are the types of agonists based on their potencies?
- Full agonist – causes maximal responses
- Partial agonist – MAY cause a lesser response when all the receptors are occupied
What is a chemical antagonist?
Chemical antagonism: antagonising molecule directly binds to or destroys the other molecule
- Uncommon among small molecule drugs
- Antibodies
- Protamine – antagonist of heparin
Describe reversible competitive anatagonism.
- Antagonist and agonist bind to the same site on receptor – very high selectivity possible
- Surmountable antagonism
- Concentration-related antagonism (higher dose - higher antagonism)
How can a partial agonist act as an antagonist?
Partial agonists have lower efficacy compared to full agonists. In the presence of partial agonist, initially the full agonist has no significant effect on the drug response. However, as the concentration increases, more and more receptors will be bound to the full agonist, achieving maximum response, albeit in a higher dose level.
Mention some pharmacologically important partial agonists.
- Buprenorphine – initial treatment for opiate dependence
- Salbutamol – beta2-adenoceptor selective agonist
- Pindolol – beta1-selective adrenoceptor (partial agonist) blocker with “intrinsic sympathomimetic activity”
Describe irreversible competitive antagonist.
- Competitive Antagonism (Irreversible)
- Maximum depressed (Insurmountable)
- Covalent or very slowly dissociating competitors
Describe the types of non-competitive antagonism.
Non-competitive (at receptor)
- Allosteric inhibitors (or enhancers)
- Binding at another site changes the conformation
- Blocks stimulus generation and response rather than binding
- Can be either:
- Mechanistic: e.g. calcium channel blockers in smooth muscle contraction
- Functional: e.g. acetylcholine and noradrenaline
Explain the concept of tachyphylaxis.
It describes an acute, sudden decrease in response to a drug after its administration, i.e. a rapid and short-term onset of drug tolerance.
Drug tolerance is a pharmacological concept describing subjects’ reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug’s effects; however, this may accelerate tolerance, further reducing the drug’s effects.
What is the right dose?
- Enough to do some good
- Not enough to do much harm
What is a therapeutic index?
Quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
