Pharmacodynamics Flashcards
Pharmacology definition and the 4 levels
The science that studies the interactions between chemical substances and living organisms
Molecular, Cellular, Organ, Organism
Pharmacodynamics definiton
The action of drugs on the body
how the drugs interact with cells and resultant physiological changes
Drug targets - regulatory proteins (4)
Enzymes
Carrier proteins
Ion channels
Receptors
Drug targets - others (3)
Nucleic acids
Lipids
Ions
3 ways drugs can interact with enzymes
Enzyme inhibitors
False substrates (drug is converted and then disrupts pathway)
Pro-drugs (inactive precursors activated by enzyme action)
How do drugs interact with carrier proteins (eg ATP pumps)
They block the binding sites preventing movement of substances across the cell membrane
How do drugs interact with Ion channels (2)
Both ways block the channel
- Entering and binding to recognition site
- Diffuse across membrane and bind to an intracellular recognition site
How do drugs interact with receptors?
Act on the ligand binding domain of the receptor
the change activates an intracellular effector domain
triggering a transduction mechanism - eg changes in cellular response or gene expression
4 main types of receptors
Ligand-gated ion channels (ionotropic)
G-protein coupled receptors
Kinase-linked receptors
Nuclear receptors
Where do drugs bind to on ionotropic receptors?
a binding site on the extracellular domain (blocking channel in milliseconds)
What are the 2 effectors drugs interact with on G-protein coupled receptors
Enzyme
Ion channel
(100ms - seconds response to due cascade of intracellular reactions)
How do drugs interactive with Kinase-linked receptors & the 2 ligands
Binds to binding domain blocking normal ligands (insulin or growth factor) from binding hampering intracellular catalytic domain activation
response in minutes
How do drugs interactive with intracellular receptors (proteins in nucleus)
ACT on DNA (‘zinc fingers’ domain) prevent protein synthesis (alter gene expression)
responses hours - days
Drug agonists explained
agonist + binding site = drug-receptor complex
a change in the receptor is induced and a response of the cell initiates
Affinity & efficacy definitions in relation to agonist drugs
Affinity - chemical forces of the binding
Efficacy - drugs ability to activate the receptors & induce a response
dose - response link
drug effect is proportional to drug concentration until maximal response is achieved (all receptors bound)
dose - response units
the % of maximal response (Emax) induced in relation to logarithmic concentration of drug
EC50 = ?
drug concentration that produces 50% of the maximal response
3 types of agonist effects
Full agonists - normal rule
Partial agonists - cant reach maximal response
inverse agonists - exerts opposite effect by supressing spontaneous receptor signalling
How is EC50 practically used
to compare the potency of different drugs acting on the same receptor (conc differences)
Agonist drug potency = ?
Agonist drug potency = affinity + efficacy
Antagonist drug definition
a drug that binds to a receptor but does no induce a conformational change or biological response
Receptor antagonist examples
Competitive (reversible & irreversible)
Non-competitive
Non-receptor antagonists
Chemical
Physiological
Pharmacokinetic
How does competitive antagonism work
Antagonist drugs have higher affinity than agonists
agonist potency = only affinity
^ agonist concentration = ?
reversible competitive antagonism
^ agonist concentration = reduced antagonist effect
how does Irreversible competitive antagonist work
antagonist dissociates very slowly or not at all
synthesis of new receptors may be required
How does non competitive antagonism work
drug binds to allosteric site preventing receptor activation (inhibits agonist response)
Chemical antagonism definition
a drug binds to a receptor ligand resulting in an inactive product lacking affinity & efficacy for the receptor
Physiological antagonism definition
2 Drugs have opposing actions via different receptor son the same tissue
Pharmacokinetic antagonism definition
Antagonism alters the pharmacokinetics of the agonist (^ metabolism rate or reducing absorption rate
