W2 L2 - Pharmacology Principles Flashcards
what’s pharmacology
Pharmacology is the science of drugs and their effect on living systems
define pharmacotherapeutics
the use of drugs to prevent and treat disease
How does a drug influence an intracellular process?
- unoccupied receptor
- drug binds to receptor
- receptor activated
- signal transduced
- biological response
define affinity
- degree of attraction
define efficacy
- degree of response
what properties will functional groups determine
- How it interacts with target
- Mechanism of action
- Route of administration
- Route of metabolism
- Ability to cause side effects / adverse effects
- They will also determine the 3D shape
what’s target interaction dependent on
- functional groups and charge distribution
- this is due to ions, dipoles and Van der Waals forces
Terms describing effects at proteins
Receptor: agonists and antagonists
Enzyme: activator and inhibitor
Transporter: activators and inhibitors
Ion channels: openers and blockers
Why do we need to understand drug-receptor interactions and behaviours?
help us understand how a drug works, what effects it will have, how side effects occur and what potential interactions there may be
define intrinsic efficacy
- capacity to excite
- excitation refers to the process where ligand binding induces a conformational or functional change in the receptor, leading to an active or stimulated state
define orthosteric binding
Molecules bind to main active binding site
define rate of dissociation
How quickly the drug comes off the receptor
what are agonists
- they activate
- have affinity and efficacy
- biased agonists activate receptor’s signalling cascade
- inverse agonists produce opposite effect of natural ligand
- all bind to same active site
what are agonists
- prevent agonist binding
- competitive - bind to same site as agonist
- non-competitive - binds to diff site
- could be reversible or irreversible (covalent bonds)
what are allosteric modulators
- Bind to different site on receptor to alter affinity and / or efficacy of the drug binding to the main site
- Can be
Positive (PAM)
Negative (NAM)
Neutral (SAM)
what’s occupation governed by
affinity
rate constants for binding and dissociating respectively
- K+1
- K - 1
what’s activation governed by
- efficacy
- activation leads to a response
2 conformational state of receptors
R - resting state
R* - active state
There’s an equilibrium between the two
KR is the rate constant
what happens at the active state
- ligand binds to active site
- biological effect
- ligand then dissociates returning receptor back to R
what happens when inverse agonists bind to receptor
- receptor remains in resting state
what are constitutively active receptors
- receptors that allow for a biological response to occur without ligand binding
What does a dose-response (or a concentration response) graph tell us?
- The effects of increasing dose / concentration of drug to see what it does to the size of the response
- dose dependent effect usually seen
- semi log scale helps look at beginning of graph more easily (easier to compare affect)
- EC50 - effect of conc that produces 50% of the maximal response
- Properties of drugs can also be determined
what’s potency
- measure of drug needed to produce a certain size of effect
- usually quantifies by EC50
- allows comparisons between drugs at the same receptor
- affinity more important than potency
- in a graph, curve furthest to the left is more potent
competitive vs noncompetitive antagonism
- in competitive increasing conc of agonist allows for maximal response
- in non-competitive antagonism increasing conc of agonist won’t allow maximal response to be reached
what’s IC50
- IC50 - inhibitory conc - how much drug is needed to inhibit a biological process by half
what is Functional (Physiological) Antagonism
- Drugs can bind to different receptors and produce opposing functional effects
- Contraction of smooth muscle
- Relaxation of smooth muscle
