Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

biochemical and physiological effect of drugs and their mechanism

Question 2

What is the mechanism of action?

Answer 2

initial interactions between drug and cellular macromolecules

Question 3

Most drug receptors have what type of ligand?

Answer 3

endogenous

Question 4

What are the non-receptor mediated drug actions?

Answer 4

• gastric antacid
• mannitol (osmotic diuretic)

Question 5

Most drugs have what types of reversible forces?

Answer 5

• ionic
• hydrogen
• hydrophobic
• van der waals

Question 6

What is the 2 state model?

Answer 6

• agonists bind and stabilizes in the active configuration
• population shifts to the right when agonists are present

Question 7

When does basal activity occur?

Answer 7

when more receptors are active

Question 8

An inverse agonist favors which side?

Answer 8

left side

Question 9

What are the mechanisms needed for signal transduction?

Answer 9

• ion channels
• receptor coupled G-proteins
• receptors with intrinsic enzyme activity
• receptors that are internalized to deliver receptor complexes to intracellular targets

Question 10

What are the characteristics of nicotinic Ach receptors?

Answer 10

• made of 5 subunits
• every subunit goes through the membrane 4 times
• subunits are higly homologous
• binding of receptor allow Na+ and K+ to flow across membrane

Question 11

What type of receptor is a partial agonist?

Answer 11

GABA

Question 12

Binding to a GABA receptor results in what?

Answer 12

pore opening and allowing Cl- ions across the membrane to cause hyperpolarization

Question 13

What are the drugs that modulate GABA receptors?

Answer 13

barbituates and benzodiazepine

Question 14

Glycine and glutamate are what type of ligand channels?

Answer 14

glycine: inhibitory
glutamate: excitatory

Question 15

A transient change in the voltage across membrane can trigger what?

Answer 15

opening of gate allowing Na+ ions across membrane

Question 16

Where do local anesthetics bind?

Answer 16

to the intracellular domain of voltage-gated Na channel

Question 17

What is the purpose of receptor coupled G-proteins?

Answer 17

regulate generation of intracellular second messengers

Question 18

What are the 3 types of G-proteins?

Answer 18

alpha, gamma, beta

Question 19

What are the enzymes coupled to G-proteins?

Answer 19

• adenylyl
• cyclase
• phospholipase C

Question 20

What are the channels coupled to G-proteins?

Answer 20

Ca++ and K+

Question 21

What 2 things can regulate the activity of other enzymes?

Answer 21

cAMP and Ca++

Question 22

What is a ligand regulated transmembrane enzyme?

Answer 22

tyrosine kinase receptor

Question 23

What is an intracellular receptor and where does it bind?

Answer 23

steroids; bind inside the membrane

Question 24

When a durg is more potent, where is it located on the graph?

Answer 24

furthest to the left

Question 25

Partial agonists have a lower what compared to fulla agonists?

Answer 25

lower efficacy

Question 26

What is the EC50?

Answer 26

* the conc. that produces 1/2 the max effect * measures potency

Question 27

If the drug needs less conc. for same EC50 then?

Answer 27

increase potency

Question 28

What is an agonist?

Answer 28

drug or ligand that binds to the same site as endogenous ligand and produces a signal

Question 29

What does a full agonist have affinity for?

Answer 29

ONLY for active state

Question 30

What does a partial agonist have affinity for?

Answer 30

higher affinity only for active than inactive state

Question 31

What is efficacy/intrinsic activity?

Answer 31

properties of durgs that bind to the same receptor site but DO NOT produce equal maximum effects

Question 32

What is the most efficacious agonist?

Answer 32

drug that produces greatest maximum effect

Question 33

What is an antagonist?

Answer 33

drug that binds to the site used by endogenous ligand and blocks the signal produced by the endogenous ligand

Question 34

What is the difference between agonists and antagonists when it comes to the binding states?

Answer 34

agonists change the equil. to active while antagonists DO NOT

Question 35

What are the characteristics of competitive antagonists?

Answer 35

* reversible * inhibition overcome by increasing the conc. of an agonist

Question 36

What are the characteristics of noncompetitive antagonists?

Answer 36

* irreversible * prevents agonist, at any conc., from producing a maximum effect on a given receptor

Question 37

When looking at a graph, what is the movement of competitive antagonists?

Answer 37

shift from left to right

Question 38

When looking at a graph, what is the movement of noncompetitive antagonists?

Answer 38

has a decrease, line gets closer to 0

Question 39

What is an inverse agonist?

Answer 39

reduce constituitive activity of a receptor

Question 40

An inverse agonist has affinity for what?

Answer 40

ONLY for inactive state (shifts the equil.)

Question 41

On a graph how would you differenciate between the types of antagonists and agonists?

Answer 41

* full agonist: at the very top * patial agonist: halfway between 0 and full agonist * antagonis: at 0 * inverse agonist: below 0

Question 42

What is receptor desensitization?

Answer 42

when continued exposure ot the same conc. of the drug diminishes the effect as a function of time of exposure to the agonist

Question 43

Continuous exposure to an agonist can what?

Answer 43

decrease the number of receptors

Question 44

Continuous exposure to an antagonist can what?

Answer 44

increase the number of receptors

Question 45

What is responsible for pharmacodynamic tolerance?

Answer 45

receptor desensitization and down regulation

Question 46

What is required to produce a given magnitude of effect and what is it known as?

Answer 46

increasing doses of drugs; tachyphylaxis

Question 47

What are spare receptors?

Answer 47

when the max effect is reached with a small fraction of the receptors

Question 48

What gives the terapeutic index?

Answer 48

ED50

Question 49

What is ED50?

Answer 49

median effective does that causes 50% of individuals to have an effect

Question 50

What is LD50?

Answer 50

median lethal does that kills 50% of tested animals

Question 51

What is TD50?

Answer 51

dose that produces toxic effect in 50% of individuals

Question 52

For a drug to be safe, what is the ratio we need?

Answer 52

a high TD50 and a low ED50