how do drugs work

Question 1

what is the plasma mebrane

Answer 1

a selectively permeable barrier between the extracellular environment and the cytosol

Question 2

what are the components of the plasma membrane

Answer 2

Na+, K+, Ca2+, Cl-, Glucose

Question 3

is there a similar amount of calcium inside and outside the cell

Answer 3

no

Question 4

is there more calcium inside or outside the cell

Answer 4

outside

Question 5

how do drugs work

Answer 5

once they arrive at the proper site of action, they bind to receptors

Question 6

where are receptors usually located

Answer 6

on the outer membrane of cells

Question 7

what does the binding of drugs to receptor do

Answer 7

it can sometimes trigger activation of enzymes located within the cell

Question 8

what type of proteins are receptors usually

Answer 8

integral membrane proteins at the plasma membrane, can also be found inside the cell

Question 9

what do receptors do

Answer 9

recognise and bind to specific chemicals (ligands, agonists/antagonists) which invokes response

Question 10

can receptor numbers change

Answer 10

yes they can be increased (up-regulation) or decreased (down-regulation)

Question 11

why would up regulation or down-regulation occur

Answer 11

in response to a chronically low or high concentration of the agonist to optimise sensitivity

Question 12

what two properties do agonists have

Answer 12

1. affinity - strength of binding to receptor
2. efficacy - intrinsic activity

Question 13

what does efficacy do

Answer 13

induces a conformational change in the receptor and activation of a response

Question 14

what property does an antagonist have

Answer 14

has affinity

Question 15

what does an antagonist do

Answer 15

blocks the receptor

Question 16

why can’t antagonists activate a response

Answer 16

they don’t have efficacy

Question 17

examples of antagonists

Answer 17

anti-histamines, beta-blockers

Question 18

when does down-regulation occur

Answer 18

in response to chronically high concentration of ligand.

Question 19

what does down-regulation do

Answer 19

decreases the sensitivity of the cell response to frequent or intense stimulation

Question 20

when does up regulation happen

Answer 20

in response to very low levels of a ligand

Question 21

what does up regulation do

Answer 21

increase sensitivity

Question 22

what underlies disease processes

Answer 22

aberrant cellular signalling

Question 23

does the intercellular signal chemical (first messenger) enter the cell

Answer 23

no

Question 24

what does binding of the signal chemical to the receptor do

Answer 24

initiate a series of chemical changes (activation of intracellular second messenger) in the cell

Question 25

what does signal transduction enable

Answer 25

amplification

Question 26

steps of signal transduction

Answer 26

1. direct opening of ion channels
2. direct activation of an enzyme
3. indirect activation/inactivation of enzyme, indirect opening/closing of ion channel
   involves a g-protein
4. intracellular second messengers involved include: Cyclic nucleotides (eg cAMP)
   Inositol triphosphate and diacylglycerol and Ca2+

Question 27

what are 3 G-protein component

Answer 27

1. seven transmembrane receptor where the ligand binds
2. G-protein (‘switch’ coupling receptor to effector enzyme)
3. effector enzyme

Question 28

what does GTP bound mean

Answer 28

the G protein is on

Question 29

What does GDP bound mean

Answer 29

the G protein is off

Question 30

how does a G protein switch itself on and off

Answer 30

the protein itself is an enzyme which converts GTP to GDP and thereby switches itself on and off

Question 31

what is the first signal following fertilisation

Answer 31

calcium signalling

Question 32

is Ca2+ ever produced or destroyed

Answer 32

no it is moved between compartments

Question 33

what does the effects of Ca2+ depend on

Answer 33

concentration

Question 34

what are the actions of calcium

Answer 34

• activation of specific protein kinases, ion channels
• regulation of activity of many enzymes

Question 35

what can Ca2+ channel blockers be used to do

Answer 35

modulate muscle contractions

Question 36

what do Ca2+ release channels do

Answer 36

release Ca2+ into the cytosol in response to an increase in intracellular IP3 or Ca2+

Question 37

what is the functional effect of Ca2+ release channels

Answer 37

contraction, proliferation

Question 38

what are targets for histamine receptors

Answer 38

parietal cells - decreased gastric acid secretion

Question 39

what are targets for opioid receptors

Answer 39

myenteric plexus/opioid receptors - decreased peristalsis, increases tone of anal sphincter (partly via Ca2+ channel blockade)

Question 40

example of drug that targets histamine receptors

Answer 40

ranitidine

Question 41

examples of drugs that targets opioid receptors

Answer 41

loperamide

Question 42

what can cause drug side effects (receptor based)

Answer 42

when enzymes bind to receptors found in more than one place in the body

Question 43

why is there low levels of calcium intracellularly

Answer 43

because calcium is a trigger for many functions

Question 44

what do you need to consider when designing drugs

Answer 44

absorption, distribution, metabolism, excretion (ADME)

Question 45

how do receptors work as second messengers

Answer 45

chemicals enter cells and bind to the receptors which changes the confirmation of that receptor

Question 46

what is the GI tract predominantly made up

Answer 46

smooth muscle

Question 47

how are calcium ions kept low

Answer 47

by storing them in many different areas

Question 48

what is a key factor in triggering relaxation in smooth muscle contraction

Answer 48

nitric oxide