drug design 2

Question 1

what is lead optimisation

Answer 1

aims to mamimize the interaction of a drug with its rarget binding site in order to improve activity, electivity and to minimize side affects

Question 2

what does structure based drug design

Answer 2

uses X-ray crystallogrpahy and computer based molecularmodelling to study its binding

Question 3

how can drug optimaistion be achieved

Answer 3

• variation of sbsituents
  -exentision of structure by isosceles and biosteres
• simplification of the structure

Question 4

what si the pharmacetical phase

Answer 4

disintergration and dissolution, determiens amount of drug avalible for absorption

Question 5

what is the pharamkinetic phase

Answer 5

ADME, deternmines amount of drug avalaible for action

Question 6

What is the pharamcodynamic phase

Answer 6

interactions with the tissue, dtermines indcution of therpuetic effect, what the drug does to the body

Question 7

what are examples of enteral routes of administartion

Answer 7

• oral
  -retal
  -vaginal

Question 8

what is parental routes of admistration

Answer 8

• intravenous, intramuscular, subcutaneous

Question 9

if it is oral what do you want the drug to be

Answer 9

inactive so its activited, if its active liver would inactivate

Question 10

why should you only take one therapy at a time sometimes

Answer 10

the p450 are all occupied

Question 11

what are dosage form

Answer 11

• lquid formualtuoin
• semisolid formulations
• solid formulations

Question 12

what is the objective of pharmakinics

Answer 12

optimisation of avalibilty

Question 13

what factors influecne how drug reaches its target

Answer 13

• hydrophilic/ hydrophobic character (want slighlty more hydrophobic)
• ionisatiobn
• size
  chemical and metabolic properties

Question 14

what are the partition steps drugs will go through

Answer 14

• elave aqueous extracellualr fluid
• passing through lipid membrane
• entering aqueous enviroments before reaching receptor

Question 15

which enzyme normally breaks down drugs

Answer 15

P450

Question 16

what are the problems relating to metabolsim

Answer 16

• metabolites have different properties to og drug
• loss of activity
• more toxic
• activity of enzyme varies

Question 17

what is a pharmacophore

Answer 17

minium structural requirements to have biological activity

Question 18

what is the role of structure-activity relationship in drug design

Answer 18

changing things like functional groups

Question 19

what is a drug receprtor

Answer 19

Specialised target macromolecule presnet on the cell surface or intracellularly that binds and mediates is pharmacological action

Question 20

what are the drug targets

Answer 20

• enzymes
• receptors
• carrier proteins
  -structural prtoeins
• nucleic acid
• lipids
• carbohydrates

Question 21

what are agnosists

Answer 21

mimic the chemical messsenger

Question 22

what are antagonist

Answer 22

• bind to receptor
• dont activate
  block binding

Question 23

what is potentiation

Answer 23

a bigger affect than you would have normally got

Question 24

what is the most common membrane bound receptor

Answer 24

G- coupled receptors

Question 25

what are the types f interaction betwen drugs and receptors

Answer 25

- ionic - h binds - van der Waal thsi depends on the fucntion groups and the charges

Question 26

what allows receptor interactions

Answer 26

- drugs must have correct binding groups - groups must be corrcetly positioned - drug needs t be correct size for binding site

Question 27

what factors influence binding and action

Answer 27

- molecular structure - isomerism - fcuntional groups - rigidity

Question 28

what is the pharamacophore

Answer 28

- which part of molecular are importat to biological activity - which functional groups are important to bonding to receptors

Question 29

what is pharmakinetic optimisation

Answer 29

optimising acess to the target

Question 30

what is the pharamdynamic optimisation

Answer 30

optimising target interactions

Question 31

modifciations that affect solubilty

Answer 31

- add ioniazble centre - increases polaroaty -decreases lipocicity

Question 32

modification to permeabilty

Answer 32

- reduces polarity - increase lipophilicty - prodrug approaches

Question 33

what would make a drug cross the blood brian barrier

Answer 33

pro drug approach increases lipophoicity

Question 34

what is a pro drug approach

Answer 34

putting the drug as one thing and the it acting as something else

Question 35

how many rings has morphone got

Answer 35

5

Question 36

how do you make codine out pf moprphine and whats the difference

Answer 36

reduction in pain relief to 20% chnage a free hydroxyl group to CH3

Question 37

how do you have to administer codeine

Answer 37

cannot do if injected stright into CNA, instead need to be oral as needs liver

Question 38

what happens whern you remove 6OH and replace with acetyl group

Answer 38

get more activity and can pass through to brain at higehr conc as less poalr

Question 38

what happens whern you remove 6OH and replace with acetyl group

Answer 38

get more activity and can pass through to brain at higehr conc as less poalr

Question 39

how is diamoprhone (Heriorin) made

Answer 39

take phenol OH and alchohol group and put acteyl groups on and improves blood brain barrier

Question 40

what is viutal to the pain releif of morphine

Answer 40

nitrogen (ionic bonding) aramatic ring (van der waals) phenolic OH (H bond) the postioning of the drug

Question 41

what are the most common drug targets

Answer 41

- enzyme - receptors

Question 42

what does it mean if a drug is charged

Answer 42

cant travel across membranes

Question 43

do you want your drug to be slightly hydrophilic or hydrophobic

Answer 43

slighty more hydrophobic

Question 44

what do the typess of intercations between the drugs and the receptors depend on

Answer 44

fucntional groups

Question 45

what interctaions might a drug have

Answer 45

- ionic -ion dipole -h bonds

Question 46

what is isomerism

Answer 46

same structure but different arrangemennt

Question 47

what is an exmaple of ligand based drug design

Answer 47

morphine

Question 48

how do you look at structure active relationships

Answer 48

take the lead and change its structure

Question 49

how is codine made from morphone and what is its actitivity

Answer 49

the phenolic OH is replaced with methyl ether and activity is 20% of morphine

Question 50

how do you increase the potency of morphone and what can it do

Answer 50

swap the 6-OH with 6-acetyl and increases analgesic affects as less polar could potneially move across blood brain barrier

Question 51

how do you make heriorin from morphine

Answer 51

swap phenolic oh to acetl group as well as 6 OH tho acetyl group get herorin this can cross blood brian barrier and very hydrophobic

Question 52

what is crucial to analegiscal activity in morphine

Answer 52

the nitrogen and ring, the phenol OH and 6-oh