Lecture 2 Semester 2 Flashcards
hungover probably need to redo this lecture
LO :
Receptor concepts, receptor classification, superfamilies.
Know what law of mass of action is, define occuoancy and affinity, log dose-response curve, define potency and efficacy
‘Problem’ of receptor signalling
Small signalling molecules are so small, how do they initiate a response in us?
Blue whale vs Midge
How can we regulate cell function
- Alter membrane potential (how so though)
- Alter enzyme activity
- Alter gene expression
Drugs i may need to know off top of my head
- Tetrodotoxin (TTX)
- aspirin (target receptor enzyme is cyclooxygenase)
- acridine dyes
- Nifedipine (Ca2+ Channels are blocked by this) (why)
- Cocaine (blocks noradrenaline transporters)
What do drugs target
Mostly receptors (broad)
More specifically,
- Enzymes
- Ion channels
- Transporter pumps
- ‘Physiological’ receptors (ACh, Histamines, insulin receptors, any hormones or neurotransmitters)
Remember drugs can act with multiple receptors
for understanding
Drugs dont always act as expected, example here
What are the types of receptor ‘superfamilies’
Integral (ligand-gated) ion channels
- Eg. Nicotinic receptor
G Protein coupled receptors
- Eg. Muscarinic receptors, adrenoreceptors
What is quantitative pharmacology
know what this bullshit is
Law of mass action shite
More mass action
more
Affinity, definition
* Affinity of a drug for its receptor is a measure of how well it
binds to the receptor
* can be measured using a drug’s dissociation constant from its
receptor, the Kd
* Kd equal to the concentration at which, at equilibrium, half the
receptor population will be bound with drug
EC50
Defined as,
Effective concentration to produce 50% of the maximum
response
Allows measure of potency
Defined as, the amount of a drug required to produce a
particular level of effect/response
Agonists
- Agonists bind to a receptor/target and produce a
response - Is response always proportional to occupancy?
- No, efficacy is also important
Efficacy Summary
Efficacy - summary
* Efficacy is a measure of the degree to which an agonist
produces a response when binding a given proportion of
receptors
* For a full agonist, the efficacy is 1
* For a partial agonist, the efficacy is less than 1
(but greater than zero)
Efficacy – further detail
* low efficacy, partial agonists cannot produce the cell’s maximal
response, even when bound to all available receptors
* some highly efficacious agonists can produce a maximal
response without binding to all available receptors
- this is evidence of ‘spare receptors’
Negative Efficacy
- it is possible to have a negative efficacy, i.e. less than
zero - drug is called an inverse agonist
- such drugs inhibit any intrinsic receptor activity that
might exist in the absence of a ligand
