What is potency?
The concentration at which a drug is effective (determined by affinity of drug for receptors, its efficacy & the receptor reserve)
n.b. this is in relation to another drug!!
What is affinity?
How well a drug binds to its receptor
What is efficacy?
How efficiently a drug elicits a response in cells
Which enzyme terminates ACh action?
Name an anticholinesterase drug?
Neostigmine (prolongs presence of ACh in cleft = indirect sympathomimmetic)
What is the action of Carbidopa?
inhibits the intracellular enzyme required for NA synthesis (prevents excesss NA release) = Parkinson's
What is Sildenafil used to treat (3)?
pulmonary hypertension High altitude sickness erectile dysfunction
What type of receptors are GPCR's?
What is pharmokinetics?
how the body deals with a drug
What are the 4 different receptor superfamilies?
- Tyrosine Kinase
What is specifity?
how selective a drug is
n.b. no drug is truly selective (higher concentrations often increases other actions)
What does the dissociation constant show?
the concentration of drug that occupies 50% of receptors
What does a lower dissociation constant show us about the efficacy of a drug?
(less drug is needs to be added before 50% of receptors are bound)
How do you calculate the dissocaiation constant?
How do you work out fractional receptor occupancy?
In which 5 conditions is the fractional receptor occupancy equation valid?
- Receptor drug concentration the same as that applied to the system
- 1 drug combines to only 1 receptor
- a negligible amount of drug added is bound
- binding of 1 drug molecule doesnt influence another (no cooperativity)
Which direction does a concentration response curve shift with a drug of lower efficacy?
(EC50 increases and receptor reserve decreases)
How do we calculate response?
What is the EC50?
The concentration of drug that gives 50% of that drugs maximum response
On a concentration response curve which side of the dissociation constant does the EC50 lie?
(you dont occupy 50% of the receptors to get 50% the biological response -> often binding = cascade of events)
What is partial agonism?
A drugs maximum response is less than the full response the tissue is capable of
(no receptor reserve)
With partial agonists how do we need a few or lots of receptors to have an effect?
(e.g. salbutamol -> lots of beta 2 receptors in lungs)
What are the 4 different types of antagonism?
- Un-competitive (activation state changes -> exposes binding sites)
- Physiological (reversal mechanisms e.g baroreceptor reflex)
In competitive antagonism what happens to the concentration response curve?
It shifts parrellel to the right
(more agonist is needed to get the same response = no reduction is max response!)
What are the 3 different ways of competititve irreversible antagoism?
- Allosteric modulation
- Ligand gated channel blockers
- Block later in pathway from receptor activation to response (e.g. enzyme inhibitor or Ca channel blocker)
What is the theory of constitutive activity?
Some receptors have a constitutive (resting) level -> becomes active on its own can agonise to produce response but can use inverse antagonist = no response
what is tolerance?
Repeated drug administration leading to adaptive downregulation of receptors to that drug
n.b. this is how some drugs (anti-depressants work -> downregulate serotonin reuptake channels)
What happens over time follwoing desensitisation?
Channels recover to normal level of response