Drug Targets Flashcards
TIER
4 methods by which drugs function
- Receptors
- Ion channels
- Enzymes
- Transporters (protein in nature)
With drugs, they apply to mostly protein targets with the exception of…
Targets of chemotherapy - often bind to DNA
Name the top 5 MOAs of drugs
- Enzyme inhibitor
- Receptor agonist
- Receptor antagonist
- Transporter blocker
- Ion channel blocker
What are receptive substances
There is a substance or substances in the nerve endings or gland cells with which both atropine and pilocarpine are capable of forming compounds
Receptive side chains to which chemical substances bind to produce effects - such binding involves weak bonds
What is propranolol
A beta receptor antagonist
What are H2 receptor antagonists
Anti-ulcer compounds
What is the MOA of aspirin
Inhibits the action of prostaglandins - substances that are liberated when tissues are perturbed producing inflammation, pain and fever in the body
(specifically inhibits the enyme cyclooxygenase that is responsible for production of prostaglandins)
What is a side effect of low dose aspirin
Stops the production in platelets of thromboxane, which causes platelets to stick together to plug any ruptures in BVs
What are receptors
What are they in nature
What do they do
Where are they found
- Recognition molecules for chemical mediators
- Large proteins (specialised structure)
- Linked to other molecules within the cell & trigger a response in that cell
- Found on cell membrane surface, cytosol, nucleus
What are endogenous ligands
What are they similar to
Give an example
- The body’s own ‘drugs’
- Drugs bind to receptors in the same way that endogenous ligands bind to receptors
- e.g. adrenaline is the endogenous ligand for beta receptors - isoprenaline (isoproterenol) is a synthetic drug that binds to the same receptor
What is adrenaline the endogenous ligand for
Beta receptors
Name the synthetic drug that binds to beta receptors
Isoprenaline (isoproterenol) is a synthetic drug that binds to the same receptor
Explain ligand specificity
How many receptors can a drug bind to
- Lock and key
- Receptors are specific for a particular ligand or drugs
- A drug may bind to more than 1 receptor
What is amitriptyline
What is its MOA
What does it bind to
- Amitriptyline is a tricyclic antidepressant
- MOA is inhibition of the neuronal reuptake of noradrenaline and serotonin
- Also binds to other targets such as the muscarinic and histamine H1 receptor
What does specificity depend on
Shape, which depends on folding in response to pH, water, lipid etc
How does drug-receptor binding occur
Multiple chemical interactions, the sum of which provides specificity
Specificity of drugs
No drug is completely specific
What is affinity
Favourability of the interactions i.e. amitriptyline has a high affinity for a number of drug targets
What is adrenaline’s receptor
B2 receptor
What are the 2 main drug-receptor bonds
- Van der Waals
- Hydrogen bonds
What are the 4 characteristics that affect binding
- PHYSICAL NATURE: solid, liquid, gaseous, organic, inorganic
- DRUG SIZE: range from very small to very large (most MWs lie between 100-1000)
- DRUG REACTIVITY: electrostatic bonds with target
- DRUG SHAPE: chirality (stereoisomerism), more than half of drugs are chiral molecules (exist as enantiomeric pairs)
What is Imatinib
What does it interact with & how
What does its binding with its receptor cause
- Imatinib is a highly selective inhibitor of the BCR-Ab1 tyrosine kinase fusion protein
- Imatinib interacts with specific AA residues that possess hydrophobic side chains via van der Waals forces and hydrogen bonding
- The binding causes a conformational change in the active site of the enzyme, inhibiting its catalytic activity
Define affinity
What is it measured by
What does it enable us to do
- The strength of the reversible interaction between a drug and its receptor
- Tendency of a drug to bind to a receptor
- Measured by Kd
- This measurement enables us to compare the affinities of drugs i.e. how avidly they bind to their target receptors
What is occupancy
The rate at which drugs (D) combine with their receptors (R) depends on the combination of drug and receptor
The rate of dissociation depends on the number of complexes (DR) formed
What is the Law of Mass Action
Explain drug-receptor occupancy curves
As the conc of drug in the vicinity of its receptor is increased, then the proportion of receptors occupied increases
As there are a finite number of receptors, a conc point will be reached when all of these receptors are occupied
* a sigmoid curve is created
What is Bmax
What is Kd
- Bmax = density of receptors at maximum binding
- Kd (equilibrium constant) = conc of drug required to occupy 50% of receptors
