Pharmacodynamics Flashcards
Pharmacodynamics
What the drug does to the body
For drugs to reach their target
Bind to outside proteins (membrane receptors), taken from transporters, diffuse through membrane (hydrophobic)
Ionotropic receptors: ion channels 3 major types
Ligand; binding to ligand channel; altered ion conductance
Voltage; change in voltage gradient; altered ion conductance
Second messenger regulated; binding of ligand to transmembrane receptor w/ G protein-coupled cytosolic domain, leading to second messenger generation; second messenger regulations ion conductance
Metabolic receptors: G protein-coupled receptors
Receptor binds; GDP pops out so GTP can bind and stimulate the effector or enzyme(PLC)..
Gs
Receptor: B1, 2-adrenergic amines, histamine, serotonin
Effector/second messenger: Adenylyl cyclase: (+) cAMP
Gi
Receptor: a2-adrenergic amine M2, Muscarnic acetylcholine opiods, serotonin
Effector/second messenger: adenylyl cyclase: (-) cAMP K+ channels: hyperpolarize
Gq
Receptors: M2, 5 mAcetylcholine, serotonin
Effector/second messenger: Phospholipase C:IP3, DAG, Ca2+
Gas Vs Gai Signaling
Little difference in them other than where they bind; the dominant effect is most important!
site of action determines outcome
ex: flight/flight- a lion attacking stimulates the sensory cortex, which moves to the brain stem, which then produces NE which can bind to BAR and BAR* which then triggers either Gas-GDP or Gas-GTP which then signals Adenylyl cyclase which then has ATP trigger cAMP (second messengers) which then has PKA trigger PKA* (which can stimulate neurotransmitter release+ increase heart contractility)
sensory cortex produces NE, which can stimulate neurotransmitter release/ heart contractility
Dimorise
Which ligand binds it changes so it has more binding power- it comes together.
phosphorylation
causes change in protein- can help change signals; it can activate or inhibit pathways, or start signaling cascade
What happens during exercise and fasting?
protein kinase A activates glycogen synthase a+b. B inactivates the storage form of glucose. Phosphorylase a also activates glycogen
Intracellular receptors
can go through the membrane and bind to a transcription factor- once it binds it can change what happens in the cell. Ex: steroids//birth control
tyrosine kinases
Binds to receptor, activates enzymes(tyrosine kinases), which then cross phosphorylates the tyrosine residues, which changes their structure which lets them change to bind to specific types of proteins or second messengers.
What kind of drugs does Ligand, G-protein coupled receptors, and tyrosine kinase receptors work on?
Hydrophilic large drugs
What kind of drugs are for the intracellular receptor?
Small, hydrophobic; steroids,
Dose-response relationship; Potency
as the graph goes up, eventually it will have to peak and stay constant because there will be no more receptors for the drug to bind to. Correlational to affinity. Affinity increases, potency increases
Dose-response relationship; efficacy
Depends on the drug-receptor interaction; how many receptors is it occupying? What is the intrinsic activity? Will it produce 100, 70, 10% of an agonist?
- so even if 100 % (full agonist) of the receptors are occupied, and the intrinsic activity, it would have the Emax(would be at 100%)
-If it is 100, but the intrinsic activity is less, the Emax would be less and show the difference in efficacy.
(shift up/down =efficacy)
(left/right =potency)
EC50
The concentration will reach 50% of the maximum effect. measure of potency or affinity. As it increases, you decrease EC50. IF it decreases it becomes more potent
Therapeutic index
Measures drug safety; the differences between ED50 and TD50. You want a large effect. TD50/ED50=TI
ED50
dose of to give to get the clinically desired effect.
TD50
Dose of drug that gives toxic effect
Hey Guy Warning These Drugs Are Leathal
gentamicin, warfarin, theothen, digoxin, AEDS, lithium
KD
binding constant… ED50 is measure of effect.
full Agonist, partial, and inverse
Full: able to produce the same intensity just like the other drug.. 100% of receptors bound and has 100% of emax effect.
Partial: Bind onto receptors, even with saturation of 100% it doesn’t produce same maximal effect(efficacy)- 70% of the effect.
Inverse agonist: bind, and decrease effect; less than 12%(less than basal activity). Inactivates the receptor
Competitive inhibition partial agonist
First drug(partial) will bind to all of the receptors because it is in the same active site. So it is blocking the second drug (agonist). The only way for the second drug to work is to increase the concentration and eventually take over.
Partial agonists can act like antagonists
competitive antagonists
In order to have an effect, your agonist has to have a larger concentration to displace the antagonist out of the active site.
to do this: increase concentration heavily (increase dosage)
Increase EC50… decrease potency.. no change in emax
Ki
concentration that has 50% inhibition of receptors bound by agonist
Lower=higher affinity
IC50
The concentration needed to inhibit half of the maximum biological response of the agonist
similar to EC50 but relates to inhibition rather than activation
