MR 8 Drugs and Receptors Flashcards
How do drugs exert their effects?
By binding to a target, often protein, occasionally DNA (some antimicrobial and antitumour drugs). Most bind reversibly with receptors, binding governed by association and dissociation rates
What can be targets of drugs?
Enzymes, GPCRs, ion channels, transporters, nuclear hormone receptors, other receptors
How much is a mole?
6x10^23 particles.
What is a molar solution?
Solution containing 1 mole in 1 litre
Are drugs of equivalent concentrations by weight, always the same concentration?
No but drugs of equivalent molar concentrations are
What are drugs that bind to receptors and cause a response called? What qualities do they have?
Agonists
Both efficacy and affinity
What are drugs that bind to receptors but don’t cause a response called? What qualities do they have?
Antagonists
Affinity only
What is affinity?
Likelihood of a ligand binding to its target
What is intrinsic efficacy?
Likelihood of activation
How is binding information often obtained?
through binding of a radioligand
What is Bmax?
Maximum binding capacity
Gives info about number of receptors
What is Kd?
The concentration needed for 50% occupancy
This is a measure of affinity and a lower Kd indicates higher affinity
What are concentration response curves used for?
Measuring a response in cells/tissues
What are dose response curves used for?
Measuring a response in whole animal
What is Emax?
The maximum response
What is EC50?
Effective concentration giving 50% of maximal response.
Measure of potency
What is potency?
depends on affinity, intrinsic efficacy and efficacy.
Efficacy + affinity= potency
What is efficacy?
Likelihood of response
If two agonists have identical Emax do they have equal efficacy?
No, may differ in affinity
What does salbutamol do and why is salbutamol effective?
beta adrenoagonist used to relax the airway via the b2 receptors there.
There are b1 adrenoceptors in the heart which could be affected by salbutamol but as salbutamol has higher affinity for b2 (kd b1=20um Kd b2=1um), because of its B2 SELECTIVE EFFICACY and because of administration route b1 activation and side effects are limited
How are side effects prevented using salmeterol?
(Longer acting than salbutamol)
No selective efficacy
Prevents b1 activation through huge difference in affinity
kd b1=1900nm b2=0.55nm
What are spare receptors?
These occur when the maximal 100% response does not need 100% receptor occupancy (Ec50<Kd so 50% of max resp takes less than 50% occupancy) so some receptors appear spare
What influences whether there will be spare receptors or not?
transduction system/amplification and properties of tissue
How do spare receptors affect sensitivity?
Increase sensitivity allowing responses at low agonist concentrations therefore also affecting potency
What is a partial agonist?
Drug that cannot produce a maximal effect even with full receptor occupancy
What is the relationship between Kd and EC50 in partial agonists?
Kd=EC50
Can partial agonists be more potent than full agonists?
Yes as potency involves both efficacy and affinity
Is a partial agonist a partial agonist in all tissues?
No can differ as tissue with more receptor would give more of a response
What are the three types of antagonists?
Reversible competitive
Irreversible competitive
Non-competitive
How common is reversible competitive antagonism and can it be overcome?
Commonest and most important form in therapeutics
Yes, overcome by high agonist concentration
Why will a heroin(morphine-full agonist) addict who then takes (partial agonist)buprenorphine become ill?
Buprenorphine has higher affinity than heroin so occupies the receptors anatgonising the heroin. The buprenorphine is only a partial agonist so doesnt give maximal response so addict feels withdrawal symptoms
Give an example of a reversible competitive antagonist
Naloxone- antagonises u-opioid receptors. Used to reverse opioid mediated respiratory depression. Its high affinity means it competes effectively with other opioids like heroin
How do reversible competitive antagonists affect a concentration response curve?
Parallel shift to right
How do irreversible competitive antagonists affect a concentration response curve?
Parallel shift to right and at high concentrations suppresses maximal response as spare and needed receptors filled by antagonist
Give an example of an irreversible competitive antagonist?
Phenoxybenzamine
a1 adrenoceptor blocker used in hypertension episodes in pheochromocytoma (tumour of adrenal gland causing excessive NA secretion and vasoconstriction
What is non-competitive antagoniism?
Allosteric binding of an antagonist to a receptor
