Pharmacodynamics - Part 4 Flashcards
What is an agonist?
Drugs which alter the physiology of a cell by binding to the target and causing similar effects as the natural NTs or inducer of the receptors
What is a partial agonist?
A drug which does not produce maximal effect even when all the receptors are occupied.
An agonist has high _______ while a partial agonist has a lower ______.
efficacy (bis)
How should an H-bond be labelled?
How should a hydrophobic interaction be indicated?
How should an ionic bond be indicated?
H-bond - dashed line
Vdw - zig zag
Ionic - normal bond
Once a NT or ligand binds to the receptor, this causes a ______ in the receptor and makes a ________ interaction.
i.e. _______ fit allows for ________ interaction
change
tighter
induced
stronger
All drug actions occur due to ________ ________ between the ligand and receptor.
intermolecular interactions
An ______ will have similar intermolecular interactions as the natural compound.
agonist
Partial agonists and antagonists are sometimes useful for the study of ________ of the receptors.
subtypes
Why can a partial agonist also be called a partial antagonist?
Since the partial agonist essentially blocks the normal, maximum strength reaction from taking place - instead a weaker reaction occurs
What two compounds mimic the physiological effect of Ach?
Nicotine
Muscarine
Nicotinic acid binds to what, more strongly?
Muscarinic acid?
Ion channel - Nicotinic
GPCR - Muscarinic
Ligands that elicit a _______ biological action tend to share a similar ____-________ bonding pattern.
similar
inter-molecular
What are common characteristics of Acetylcholine and Nicotine and Muscarine?
What are these functional groups called?
(You may want to refer to slide 33 - pharmacodynamics 3)
Cationic center
Hydrogen bond acceptor
Pharmacophores
What are some possible medical uses of nicotinic Ach receptor agonists?
1 - Memory improvement in Alzheimer’s patients
2 - Controlling symptoms of Tourette’s Syndrome
________ effect is elicited by the _______ interaction.
biological
ligand
The observed leves of biological effect from drug action depend on what?
1 - The number of sites the ligand occupies (occupational theory)
2 - The rate the ligand associates and dissociates (rate theory)
3 - The ability of the ligand to induce the conformational change to the ligand-target complex
Agonists generate _______ conformational changes that produce a _________ response.
specific
biological
Antagonists produce __________ conformational changes and ___ biological response.
non-specific
no
What are antagonists?
Drugs which inhibit or block responses caused by agonists.
What is a competitive antagonist?
- Drug which competes with an agonist for the same site on a receptor/target.
Competitive agonist:
______ doses of an ________ can generally overcome _________
high
agonist
antagonist
Antagonist action:
- Antagonist binds to the ______ site but ____ to produce the correct _______ fit
- receptor is ___ _______
- _________ messenger is ______ from binding
binding, fails, induced
not activated
normal, blocked
An antagonist tends to have _______ intermolcular interactions as an agonist, and is ______ than the agonist
similar
longer
What is a non-competitive antagonist?
Drug that binds to a site other than the agonist-binding domain, and inhibits action
Non-competitive antagonist:
- Induces a ________ ______ in the receptor such that the _______ no longer _________ the ______ binding site
conformational change, agonist, recognizes, agonist
Non-competitive antagonist:
- ______ doses of an agonist ______ overcome the antagonist in this situation
high
doesn’t
What is an irreversible antagonist?
Drug that permanently binds to the receptor binding site, therefore they can not be overcome with agonist
An irrerversible antagonist would have what kind of bonds?
Non-hydrolyzable covalent bonds
_________ ________ are useful for the study of the receptor.
irreversible antagonists
An irrerversible antagonist will have a ____ Kd.
low
An irreversible antagonist will bind where?
Agonist binding site and elsewhere (Antagonist binding site)
What is an alkaloid?
Naturally extracted compound that contains a nitrogen
Describe a typical Ach antagonist.
H-bond acceptor,
N-center
Bulky structure to occupy additional sites
Reversible allosteric antagonists:
- Antagonist binds _______ to an ________ site
- ________ bonds formed between antagonist and binding site
- Induced fit ______ the shape of the receptor
- ______ _____ is distorted and is ____ recognized by the messenger
- __________ messenger concentration _______ reverse antagonism
reversible, allosteric intermolecular changes/alters binding site, not increasing, doesn't
Antagonist by umbrella effect:
- Antagonist binds ______ to a _________ binding site
- ________ bonds formed between antagonist and binding site
- Antagonist ______ with the messenger binding site
- _______ is blocked from the binding site
reversibly, neighbouring
intermolecular
overlaps
messenger
How does the antagonist block messenger binding by the umbrella effect?
Large structure blocks messenger binding through steric hindrance