chemistry

Question 1

opium alkaloids

Answer 1

aka opiates
centrally acting analgesics
strong narcotic effect

Question 2

indication of opioids

Answer 2

• moderate to severe pain
• cough
• diarrhoea
• opioid dependence

Question 3

common adr of opioids

Answer 3

respiratory depression
nausea and vomiting
drowsiness

Question 4

delta (opioid receptor) and its agonist function

Answer 4

analgesia
antidepressant
physical dependece

Question 5

kappa and its agonist function

Answer 5

spinal analgesia
sedation
miosis
inhibition of ADH release

Question 6

mu and its agonist function

Answer 6

u1- supraspinal analgesia
physical dependence

u2-respiratory depression
miosis and reduced GI motility

Question 7

nociceptin receptor and agonist function

Answer 7

anxiety
depression
appetite
toelrance to mu agonist

Question 8

body snatural antiiniceceptives

Answer 8

endorphins (EnDOgenous moRPHINES)

enkephalin
-smaller peptides

Question 9

morphine structure

Answer 9

5 rings (A-E)
T shape

Question 10

functional modificaiton of the R groups on morphine to yield codeine, ethylmorphine and 3-acetylmorphine leadsw to what in terms of analgesic activity

Answer 10

decreased analgesic activity

Question 11

how does codeine act as prodrug for morphine

Answer 11

codeien is converted to morphine in the liver

Question 12

functional modification of the 5-OH led to what in terms of activity

Answer 12

4-5 fold increase

Question 13

testing of analgesics

Answer 13

performed in vivo

many factors must be considered as to why activity increase

Question 14

ultimate resistance of opioid analgeics to CNS

Answer 14

BBB

6-acetylmorphine and heroin highly lipophilic therefore can penetrate the lipophilic bilayer and enter CNS

more polar morphine cannot readily penetrate the BBB

Question 15

how do we get dihydromiorphine

Answer 15

preapred by hydrogenation of morphine

double bond at c7-c8

activity is not comprimised therefore double bond not essential for activity

Question 16

N methyl groups in morphine functional modification

Answer 16

n-oxide or n methyl quayernary salts are ianctive in vivo as they are charged molecules therefore cannot cross BBB

Question 17

N methyl groups in morphine functional modification and interaction with the receptor

Answer 17

since molecules are permanent cationsn nitrogen must be charged wihen inteacting with the receptor

Question 18

normorphine in terms of polarity and activity

Answer 18

increased polarity therefore decreased activity

Question 19

normorphine and removal of notrigen atoms

Answer 19

leads to total abolition of activity

nitrogen atoms is essential for activity and interacts with the receptor in ionised form

Question 20

aroamtic ring in morphine

Answer 20

essentials

removal leads to loss of activity

Question 21

ether bridge in morphine

Answer 21

not required for analgesic activity

Question 22

mehtly group in morphine

Answer 22

not essential for analgesic activity

Question 23

sterochemistry of morphine

Answer 23

contains everal chiral centers

enantiomer is completely inactive

Question 24

enantiomer of morphine and why its completely inactive

Answer 24

morphine forms 3 receptor interactions with the binding regions

enenatiomer has no alagesic activity as it only has 1 receptor interaction

Question 25

eprimerixation of morphine and its effects

Answer 25

leads to drastic change in molecular shape result in poor conformation for receptor bindsing

Question 26

pharmacophore of morphine

Answer 26

3D positioning of the key function groups with respect to each other orginal structure-skeletal pharmaocophore-pharmacophoric triangles

Question 27

metabolic pathway of codine

Answer 27

morphine via o-demethylatuion norcodeine (N-demethylation)

Question 28

morphine metabolic pathway

Answer 28

N demethylaton-normorphine ugt2b7- morphine -6-glucoronide (mroe active) ugt2b7, paps-morphine 3 glucorodine or sulfate (inactive)

Question 29

which metaboltie of morphine is more reactiube than itself

Answer 29

morphine 6 glucoronide

Question 30

phase 1 reaction of morphine

Answer 30

many mu receptor agonists have an N methyl group which is readily dealkylated by CYP3A4

Question 31

nor metabolite from dealkylation

Answer 31

nor-lacking a methyl group

Question 32

why nor metabolites have limited clincial relevance

Answer 32

dicreas ein distribution enhancing lipophilicity loss of agonist promoting hydrophobic interaction witht he receptor

Question 33

patients deficient in cyp2D6

Answer 33

unable to 0-dealkylate codeine and therfore show little or no response to codeine based analgesic

Question 34

common metabolic reactions phase 2

Answer 34

phenols conjugate with either glucoroic acid

Question 35

what impacts oral bioavailability of many phenolic opioids

Answer 35

phase 2 conjugation in the GI tract

Question 36

morphine 6 glucoronide and morphine. potency

Answer 36

estimated to be 50:1

Question 37

in whom can m6G accumulate in

Answer 37

although readily excreted it can accumulate in patients with renal failure or poor renal function

Question 38

varying substittuents to develop morphine monologues

Answer 38

a series of phenolic alkylation products led to a group of poor or inactive compounds

Question 39

extending molecular structure in developemt of morphine analogues

Answer 39

drug extension is a strategy in which the molecule is extended by addition of potential extra binding groups easiest position to add substituent uto is the nitrogen atoms -N demethylation required

Question 40

in N alkylmorphines. activity of the structure if the R2 is ch2ch2Ph (phenethyl)

Answer 40

14x activity of morphine

Question 41

in N alkylmorphines activity of the structure if the R2 is pentanyl, hexanyl

Answer 41

agonists

Question 42

in N alkymorphines activity of the strucutre if the R2 is Bu

Answer 42

zero activity

Question 43

in N alkylmorphines activity of the strucure if the R2 is me, Et, Pr

Answer 43

agonism decreases antyagonism increases

Question 44

allyl and cyclopropylmethyl

Answer 44

when these groups were attached yield astounduing resutls poses no analgesic activity therefore used to tx of opiates overdose

Question 45

agonists and the equilibrium between active conformation and inactive conformation

Answer 45

switches the equilibrium in favour for the active confromation which increases signal transduction

Question 46

antagonsits and the equlibrium between active and inactive conformation

Answer 46

switches the equilibrium in favour of the inactive conformation which leads to a decreased signal transduction

Question 47

amount of rings in morphine

Answer 47

5

Question 48

loss of ring E

Answer 48

complete loss of activity

Question 49

loss of ring d

Answer 49

removal of cyclic ether formation of morphinans

Question 50

n-methylmorphinans

Answer 50

20% analgeisc activity

Question 51

levorphanol

Answer 51

5x more potent that morphine

Question 52

removal of rings c and d

Answer 52

benzomorphans retain analgesic activity

Question 53

removal of b c and rings

Answer 53

4-phenylpiperidines

Question 54

fentanyl

Answer 54

successful piperidicine deivatibe 100x more potent that morphione

Question 55

what does fentanalyl strucutre lack

Answer 55

phenolic-oh extrememly lipophilic

Question 56

removal of b c d e ring

Answer 56

methadone

Question 57

methadone in terms of severity of side effects

Answer 57

dispalays less servere emesis, constipation, sedation, euphoria

Question 58

r isomer of methadones activity

Answer 58

responsible for the analgesic activity

Question 59

s isomer of methadones activity

Answer 59

anatagonises the nmda receptor

Question 60

where is methadone beneficial in

Answer 60

neuropathic and opioid resistant pain

Question 61

why does methadone have a prolonged duration of action

Answer 61

generation of serveral active n-dealkylated and c3 redyuced metabolites some metabolites also have long t0.5

Question 62

administration of methandone

Answer 62

oral | injection

Question 63

methandone and its risk of fatal cardiac arrhythmias

Answer 63

prlonged qt interval

Question 64

tramadol

Answer 64

analgesic with multiple moa weak mu agonist

Question 65

pateitns allergic to cordine should not recieve tramadol why

Answer 65

risk for anaphylatic shock

Question 66

tramadol and enantiomer differences

Answer 66

1r, 2r enantiomer 30x more potent than 1s,2s enantiomer

Question 67

tramadol and its metabolsm which is similar to codeine

Answer 67

o-demethylate via cyp2d6 to a mroe potent opioiid rceptor agonist

Question 68

diels alder reaction

Answer 68

cycloaddition reaction between diene and dienophile to form a six membrered ring containing a double bond

Question 69

formation of oripavines

Answer 69

using methyl vinyl ketones as the dienophile intriduces reactive ketone group into molecule

Question 70

etorphine

Answer 70

1000x mroe ptoent than morphine used as tranquilizers for large animals

Question 71

bupernorphine

Answer 71

drug extension led to this good analgeisc activity