Pharmacology Flashcards
What is the definition of a drug?
“a chemical substance of known structure which, when administered to a living organism, produces a biological effect”
How do G protein coupled receptors work?
They activate a variety of signalling systems via interactions with different G proteins.
e.g. Gs activates adenyl cyclase that increases cAMP
What active compounds have been isolated from plants and animals?
- morphine isolated from opium poppies
- quinine isolated from tree bark
- atropine isolated from plant used as eyedrops
- Digoxin isolated from fox glove plant, used for your heart
Define pharmacodynamics.
The quantitative and qualitative study of how drugs interact with chemically sensitive sites (receptors)
Why are most drugs in clinical use a small molecule?
- if smaller, more likely to enter the body and be absorbed and so reach the site of action
What chemical formula is given for the interaction of a drug with its receptor?
D+R = DR
What is the Hill-Langmuir equation and what does it show?
p= [D]/ [D] + Kd
It shows the proportion of receptors occupied by a drug (p)
- the longer the drug binds the more effect
What parameter is used to measure the affinity of a drug for its receptor?
Kd
- the lower the Kd, the higher the affinity
What is an agonist?
A chemical that bits to its target to increase the activity
What is an antagonist?
A chemical that opposes the action of another chemical. This means that antagonist’s should have no action on their targets in the absence of an agonist.
What does EC50 measure?
EC50 = concentration of the agonist where half of maximal possible effect occurs
pEC50 is the -log(EC50)
What EC50 value shows a potent drug?
low EC50, high pEC50
What changes does a competitive antagonist make?
- prevents the binding of the agonist
- ‘right shift’ on graph
(difference between both lines is the CR) - increase the apparent EC50
What changes does a non- competitive antagonist make?
- binds at a different binding site from the agonist and prevents the effects of the agonist
- Curve shifts down
- does not change the EC50
Define efficacy.
Measure of the degree to which an agonist produces a response when binding a given proportion of receptors
What is the efficacy for a full agonist and a competitive agonist?
Full agonist has the efficacy of 1
Competitive agonist has efficacy of 0
What does an allosteric modulator do?
- A ligand that increases or decreases the action of an agonist or antagonist
if increases activity of the agonist it is a positive allosteric modulator
If decreases then it is a negative allosteric modulator
What shift on a graph is seen if there is a positive allosteric modulator presence?
- shift to the left
What is the therapeutic window?
The window in between the minimum and maximum toxic concentration. Where we want the duration of the therapy of the drug to be. Too high = toxic. Too low = won’t work
How do you work out the therapeutic radio?
TD50 / ED50
TD50 - toxic dose of a drug for 50% of the population
ED50 - minimum effective dose for 50% of the population
What therapeutic ratio can be seen in the safest drugs?
a high therapeutic ratio
What does ADME stand for?
Absorption - the way the drug enters the body to reach the systemic circulation
Distribution - movement of drug from systemic circulation elsewhere to the body
Metabolism - how the drug is metabolised by the enzymes in the body
Excretion - how the drug is cleared by the body
What is ADME important for?
- drug development
- understanding toxicity
- establishing route of administration
- establishing drug dose
- understanding possible drug interactions
What is the definition of Bioavailability?
Fraction of unchanged drug that reaches systemic circulation
