Exam1Lec4Pharmacokinetics

Question 1

What are pharmacodynamics?

Answer 1

The study of biochem and physiological effect of drugs and their mechanism of action

what drugs do to body

Question 2

Pharmacodynamics mechanism of action include ___

Answer 2

1. Initial interaction between drug and receptor
2. responses

Question 3

The site of drug action is often at specific protein macromolecules typically termed

Answer 3

receptors

Question 4

Most receptors have

Answer 4

an endogenous ligand

usuallt agonist,compd that produce effect on receptor

Question 5

Antagonists can be detected when?

Answer 5

When there is an agonist around

Question 6

Drug receptors are not always membrane embedded proteins but can also be

Answer 6

1. Enzymes (HMG-CO A reductaase, acetylcholinestrase)
2. Na+, K+, -ATP ase pump
3. structural proteins (tubulin)
4. Nucleic acids (for cancer chemotherapeutic agents)

Question 7

Interaction of drug receptors are

Answer 7

reversible/non convalent

drugs can bind and come off.

Question 8

Two state model

Answer 8

mostly inactive form but when you add a ligand, it binds to the active form

Question 9

example of an inverse agonst

Answer 9

antihistamines

Question 10

AMPA receptor configurations

Answer 10

receptor is “dancing” going from an active to inactive state

receptors are dynamic molecules

Question 11

what 3 things play an important role in drug/receptor interactions

Answer 11

1. Hydrogen bonding
2. Ionic
3. Hydrophobic

Question 12

General mechanisms for signal transduction

Answer 12

1. Ion channels
2. GPCR ( to regulate generation of IC second messengers)
3. Intrinsic enzyme activity (tyrosine kinases)
4. Receptors internalized (to deliver receptor-complexes to IC targets)

Question 13

example of ion channels and function

Answer 13

ligand gated
agonist ligand binds to receptor and allow flow of ions (stabalizes channel)

another ex: voltage gated

Question 14

Ligand gated ion channel examples

Answer 14

1. Nicotinic AChR (excitatory)
2. GABA (inhibitory)
3. Glycine (inhibitory)
4. Glutamate (excitatory)

Question 15

Nicotinic AChR:

excitatory vs. inhibitory?
how many subunits?
leaves how many times?
allows what ions through?

Answer 15

excitatory
Pentamer (2alpha, 1 beta, 1 delta, 1 gamma)
4 times
Na+ & K+

endog ligand=ACh

Question 16

GABA:
excitatory vs. inhibitory?
how many subunits?
allows what ions through?

Answer 16

inhibitory
pentamer
Cl-

binding of agonsits GABA will result in the openong of the pore allowing Cl- ions to flow across membrane

Question 17

Example of drugs which modulate GABA receptors

Answer 17

Barbiturates and Benzodiazepines

Question 18

Local anesthetics bind to the ____ domain of voltage gated ____ channel

Answer 18

intracellular; Na+

Question 19

GPCR can influence activity of enzymes such as ____ and channels such as ____ thereby incr or decr the lvel of IC seconday messengers such as

Answer 19

1.adenylyl cyclase or phospholipase c
2. Ca2+ and K+
3. cAMP or
Ca2+

cAMP and Ca2+ can then regulate the activity of other enzymes
GPCRs are huge targets for drugs

Question 20

How many receptors does GPCR have? spanning how many domains?

Answer 20

3 receptors
7 domains

ex: angiotensin, glucagon, histamine,opiod, serotonin, beta-adrenic, beta2-adrenic receptors.

Question 21

Example of Ligand regulated transmembrane enzymes (intrinsic enzymes)

Answer 21

Insulin and epidermal GFR
(TK receptors)

intrinsic enzymatic activities (aka, they have their own kinase activity)

Question 22

Intracellular receptors example

Answer 22

steroids (estrogen, androgen) receptors

it can alter gene expression in nucleus

Question 23

Drug receptor interaction with the following Drug binds to :
GABA receptor
GPCR
Steroid receptor

slide 78

Answer 23

Cl- amplification
cAMP amplification
mRNA amplification

Question 24

As the [ ] of a drug increase, the magnitude of effect ____

Answer 24

increases

Question 25

EC50 of a drug is the [ ] that produces _____

Answer 25

1/2 maximum effect (Emax/2)

Question 26

Explain this graph

which is the most potent and explain why
Which is the least potent and explain why
which one has the most efficacy
Label each one as either full agonist, partial agonsist, or antagonist

Answer 26

this graph represents different drugs on the same receptor.

Muscarine is most potent because it has the lower EC50 ( it takes less concentration to reach 50% of its effect)

Phenoarbital is the least potent because it takes more concetration to reach 50% of its effect

Muscarine and Gaba have the same efficacy, but we need more Gaba to reach this effect

Muscarine and Gaba are both full agonists

Phenoarbiital is a partial agonsit because it does not reach full effect.

Question 27

Explain this graph

Answer 27

This graph represent the same drug on the receptor. In this case it is an antagonist of GABA, more specifically, competitive antagonist of GABA. Its action can be reveres bc its competing for the same site as gaba. If you incr the concentration of GABA high enough, you can overcome the antagonist and get full effect.