Pharmacodynamics

Question 1

Pharmacodynamics

Answer 1

What the drug does to the body

Question 2

For drugs to reach their target

Answer 2

Bind to outside proteins (membrane receptors), taken from transporters, diffuse through membrane (hydrophobic)

Question 3

Ionotropic receptors: ion channels 3 major types

Answer 3

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

Question 4

Metabolic receptors: G protein-coupled receptors

Answer 4

Receptor binds; GDP pops out so GTP can bind and stimulate the effector or enzyme(PLC)..

Question 5

Gs

Answer 5

Receptor: B1, 2-adrenergic amines, histamine, serotonin

Effector/second messenger: Adenylyl cyclase: (+) cAMP

Question 6

Gi

Answer 6

Receptor: a2-adrenergic amine M2, Muscarnic acetylcholine opiods, serotonin

Effector/second messenger: adenylyl cyclase: (-) cAMP K+ channels: hyperpolarize

Question 7

Gq

Answer 7

Receptors: M2, 5 mAcetylcholine, serotonin

Effector/second messenger: Phospholipase C:IP3, DAG, Ca2+

Question 8

Gas Vs Gai Signaling

Answer 8

Little difference in them other than where they bind; the dominant effect is most important!

Question 9

site of action determines outcome

Answer 9

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

Question 10

Dimorise

Answer 10

Which ligand binds it changes so it has more binding power- it comes together.

Question 11

phosphorylation

Answer 11

causes change in protein- can help change signals; it can activate or inhibit pathways, or start signaling cascade

Question 12

What happens during exercise and fasting?

Answer 12

protein kinase A activates glycogen synthase a+b. B inactivates the storage form of glucose. Phosphorylase a also activates glycogen

Question 13

Intracellular receptors

Answer 13

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

Question 14

tyrosine kinases

Answer 14

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.

Question 15

What kind of drugs does Ligand, G-protein coupled receptors, and tyrosine kinase receptors work on?

Answer 15

Hydrophilic large drugs

Question 16

What kind of drugs are for the intracellular receptor?

Answer 16

Small, hydrophobic; steroids,

Question 17

Dose-response relationship; Potency

Answer 17

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

Question 18

Dose-response relationship; efficacy

Answer 18

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)

Question 19

EC50

Answer 19

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

Question 20

Therapeutic index

Answer 20

Measures drug safety; the differences between ED50 and TD50. You want a large effect. TD50/ED50=TI

Question 21

ED50

Answer 21

dose of to give to get the clinically desired effect.

Question 22

TD50

Answer 22

Dose of drug that gives toxic effect

Question 23

Hey Guy Warning These Drugs Are Leathal

Answer 23

gentamicin, warfarin, theothen, digoxin, AEDS, lithium

Question 24

KD

Answer 24

binding constant… ED50 is measure of effect.

Question 25

full Agonist, partial, and inverse

Answer 25

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

Question 26

Competitive inhibition partial agonist

Answer 26

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

Question 27

competitive antagonists

Answer 27

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

Question 28

Ki

Answer 28

concentration that has 50% inhibition of receptors bound by agonist

Lower=higher affinity

Question 29

IC50

Answer 29

The concentration needed to inhibit half of the maximum biological response of the agonist

similar to EC50 but relates to inhibition rather than activation