Lecture 4/5 - Pharmacodynamics

Question 1

What is different about how corticosteroids interact with the cell?

Answer 1

Act on nuclear receptors, altering genes expressed. this causes its effects to be expressed for several weeks even with the drugs gone

Question 2

What is an electrostatic interaction?

Answer 2

Attraction between functional groups w/ opposite charges

Can be either strong or weak depending on the charge strength

Question 3

Describe hydrogen bonds.

Answer 3

Hydrogen covalently bonded to an electronegative atom

Weak

Question 4

What tends to act on intracellular receptors?

Answer 4

Hormone/drug crosses plasma membrane

Question 5

What is commonly the effect of intracellular receptor activation?

Answer 5

As a complex, stimulates gene transcription OR removes an inhibtion

Question 6

What is the typical characteristics of intracellular receptor reaction time?

Answer 6

Normally has a lag period but will persist over time

Question 7

What five examples given in lecture activate intracellular receptors?

Answer 7

Corticosteriods 
Mineralcorticoids 
Sex steroids 
Vitamin D 
Thyroid hormone

Question 8

What is the structure of a transmembrane protein?

Answer 8

Polypeptides w/ extracellular hormone binding domain + cytoplasmic enzyme domain

Question 9

What are the three kinds of enzymes involved with the transmembrane proteins?

Answer 9

Tyrosine kinase + Serine kinase + Guanylyl cyclase

Question 10

What happens to the transmembrane protein receptors once stimulated?

Answer 10

They are down regulated

Question 11

What are three examples given in lecture of protein tyrosine kinase receptors?

Answer 11

Insulin + Epidermal GF + PDGF

Question 12

Describe ligand-gated channels.

Answer 12

Receptor is linked to an ion channel, when ligand binds channel is opened and ions rush in or out of the cell

Question 13

What ion is paired with acetylcholine/nicotinic receptors?

Answer 13

Na

Question 14

What ion is paired with GABA receptors?

Answer 14

Cl-

Question 15

What ion is paired with benzodiazepine receptors?

Answer 15

Cl

Question 16

What ion is paired with the glutamate receptor?

Answer 16

Ca or Na

Question 17

Describe a G-protein coupled receptor.

Answer 17

Coupled with G-protein to intracellular second messengers, spans the whole membrane

Question 18

What do G proteins interact with?

Answer 18

GTP, stimulate binding + hydrolysis = GDP

Question 19

What do Gs receptors do?

Answer 19

Stimulation the formation of cAMP

Question 20

What do Gi receptors do?

Answer 20

Inhibit the formation of cAMP

Question 21

What does cAMP do if it is activated?

Answer 21

PDE breaks down cAMP

cAMP also binds to intracellular protein kinases = phosphorylation of PKA + CREB

Question 22

What is a major Gs receptor?

Answer 22

Beta1

Question 23

What is a major Gi receptor?

Answer 23

Alpha 2

Question 24

What compounds stimulate Gs?

Answer 24

EPI - NE - Isoproterenol - Dobutamine - Histamine - FSH - ACTH

Question 25

What compounds stimulate Gi?

Answer 25

NE - EPI - Dexmedetomidine - Acetylcholine - Morphine - Serotonin

Question 26

What does Gq activate?

Answer 26

Phospholipase C

Question 27

What does PLC do?

Answer 27

Hyrolyze PIP2 into IP3 DAG

Question 28

What does IP3 do?

Answer 28

release calcium stores

Question 29

What does DAG do?

Answer 29

Stimulate PKC

Question 30

What compounds stimulate Gq?

Answer 30

Acetylcholine - NE/EPI - Phenylephrine - Serotonin

Question 31

How does the amount of drugs bound to receptors compare to the amount of free drug?

Answer 31

Negligible

Question 32

What is response directly related to?

Answer 32

Number of receptors occupied

Question 33

When do you get a maximal response?

Answer 33

When all receptors are being used, at this point no matter how much drug you introduce into the system it will do nothing

Question 34

What does a sigmoid dose response curve allow you to do?

Answer 34

Determine EC50 (effective concentration)

Question 35

What direction are more potent drugs on dose-response curves?

Answer 35

Left

Question 36

What does the slope tell you on a dose-response curve?

Answer 36

How fast response changes with dose

Question 37

What does the quantal dose-response curve show you?

Answer 37

Frequency of desired effect with each dose (a yes or no response) use frequency distribution plot

Question 38

What are the two components to therapeutic ratio?

Answer 38

ED50 + LD50

Question 39

What is Kd?

Answer 39

Concentration needed to produce half the maximal binding

Question 40

What is affinity ?

Answer 40

Measures the binding of drug to receptor

Question 41

What is Potency?

Answer 41

Dose require to produce a given effect

Question 42

What tells you potency?

Answer 42

EC50

Question 43

What is efficacy?

Answer 43

Degree of biological response via the binding of the drug to the receptor. NOT POTENCY

Question 44

What is intrinsic activity?

Answer 44

= efficacy, ability of the drug to initiate response | Number btwn 1 and 0

Question 45

What type of activity do agonist have?

Answer 45

Affinity + Intrinsic

Question 46

What type of activity do antagonists have?

Answer 46

Affinity + no intrinsic

Question 47

What type of activity do partial agonist have?

Answer 47

Affinity + lower intrinsic

Question 48

What is an agonist?

Answer 48

Bind to receptor and cause a response

Question 49

What is an antagonist?

Answer 49

Binds to receptor but does not cause a response, blocking the agonist from doing it's job

Question 50

What is a partial agonist?

Answer 50

Binds to receptor and causes response but not as good on one, will block the max effect of the agonist

Question 51

What are the four types of antagonists?

Answer 51

Competitive Non-competitive Functional Chemical

Question 52

What is a competitive antagonist?

Answer 52

Compete for binding site w/ agonist but with zero activity

Question 53

What effects does the competitive antagonist have?

Answer 53

Decrease affinity NO EFFECT on maximal dose response Shift curve to the right

Question 54

Can the agonist overcome the competitive antagonist?

Answer 54

Yes, in high enough doses

Question 55

What are non-competitive antagonist?

Answer 55

Bind irreversibly to receptor so agonist cannot bind, can also bind to a secondary site preventing the agonist from acting

Question 56

What are the effects of a non-competitive antagonist?

Answer 56

Max response is decreased | EC50 may or may not change

Question 57

What is a functional antagonist?

Answer 57

Acts through different receptor mechanisms to alter response, less specific and harder to control

Question 58

What is a chemical antagonist?

Answer 58

Neutralizes drug or compound

Question 59

What is a partial agonist?

Answer 59

Partial agonist produce response but w/ lower efficacy than full agonist

Question 60

For most drugs, what is the duration of activity linked to?

Answer 60

Time that drug is bound to receptor, meaning once drug is cleared from the blood stream action is terminated

Question 61

What happens when a partial agonist combines with a full agonist?

Answer 61

Competition for the receptor will occur causing a decrease in the response, causing them to look like antagonists

Question 62

What is an inverse agonist?

Answer 62

Does the opposite, physiologically, of what the Agonist does Example: if the agonist increases heart rate the inverse will decrease it

Question 63

What causes tolerance?

Answer 63

Chronic administration of drugs

Question 64

How is pharmacokinetic tolerance?

Answer 64

Drug induces its own metabolism | Drug increase metabolism of another drug

Question 65

What is pharmacodynamic tolerance?

Answer 65

Up or Down regulation of receptor