Chemistry 1

Question 1

What are opium alkaloids?

Question 2

Examples of opium alkaloid drugs

Question 3

What type of analgesics are opium alkaloids?

Answer 3

Centrally acting analgesics

Strong Narcotic effect

Question 4

Opium alkaloids have a strong ______ effect?

What does it mean?

Question 5

How many opioid compounds have been approved?

Answer 5

>50

Question 6

Clinical use of opioids

Answer 6

Mainly used for their analgesic properties in the management of acute + chronic pain

• Moderate - severe pain e.g. fentanyl
• Cough e.g. codeine
• Diarrhoea e.g. loperamide
• Opioid dependance e.g. methadone

Question 7

Name ADRs of opioids

Question 8

Describe the problem of opioid use

Answer 8

Tolerance leads to physical dependance, which leads to addiction

Question 9

How is codeine converted to morphine?

Question 10

Name the 3 major subtypes of opiate receptor

Question 11

Which opiate receptor is common?

Answer 11

Mu-opioid receptor

Question 12

Delta agonist function

Question 13

Mu1 agonist function

Answer 13

Supraspinal analgesia + physical dependance

Question 14

Mu2 agonist function

Question 15

Kappa agonist function

Question 16

Agonist function of nociceptor

Question 17

Name the body’s natural painkillers + where they are produced

Question 18

Name the 6 stages of narcotic analgesic development

Question 19

Shape + no. of rings in morphine structure

Question 20

How do we test analgesics?

Answer 20

In vivo (in living organism)

Question 21

Why does in vivo analgesia decrease?

Question 22

What prohibits CNS receptor access?

Question 23

How comes heroin can enter CNS easier than morphine?

Question 24

How many chiral centres does Morphine have?

Question 25

Why is morphine's enantiomer completely inactive?

Question 26

What is epimerisation?

Question 27

What is pharmacophore?

Question 28

Draw common metabolic reactions of morphine

Question 29

What functional group does Mu-receptor agonist have and how is it dealkylated?

Answer 29

Mu-receptor have an N-methyl group which is dealkylated by CYP3A4

Question 30

Why are non-metabolites limited therapeutically?

Question 31

Why do some patients not respond to codeine-based analgesics?

Question 32

Phase 2: What do phenols conjugate with? What type of patients have those conjugates found in their urine + are they active?

Answer 32

Phenols conjugate with either glucuronic acid or sulfate Both conjugates found in urine of patients taking multicyclic opioids Mainly inactive

Question 33

Phase 2 conjugation impacts on \_\_\_\_\_\_\_

Question 34

What has a higher potency than morphine + by how much?

Question 35

What is a drawback of M6G?

Question 36

What are the 4 strategies for morphine analogue development?

Question 37

What is vary substituents?

Question 38

Describe molecular structure * What is the easiest position to add substituents? * What does semi-synthesis require? *

Question 39

Draw synthesis of N-alkylated morphine analogues

Question 40

Functionalisation of 2ndary amine using alkyl halides leads to a range of N-alkylmorphines What alkyl morphines cause: * increase in antagonism? * 0 activity? * agonists? * 14x activity of morphine?

Question 41

How was Naloxone produced? What is the clinical use of Naloxone?

Question 42

In simplification, _____ complexity causes ________ of synthesis

Question 43

Which 5 rings in the morphine skeleton has no activity if it is removed?

Answer 43

E

Question 44

Name structure if: * D is removed? * C + D is removed? * B, C + D is removed? * B, C, D + E is removed? All of the rings above have been removed but which one has a rapid onset of analgesic action but short onset?

Question 45

Which levorphanol isomer has little/no activity?

Answer 45

(+) isomer

Question 46

If we want to extend morphine, what do we add to form a: * antagonist? * increase activity?

Answer 46

Antagonist = allyl on N Increase activity = phenethyl

Question 47

Which simplified morphine analogue causes higher toxicity than morphine?

Question 48

Example of a 4-phenylpiperidine + describe clinical use

Question 49

Name a successful piperidine derivative + explain why it is good

Answer 49

Fentanyl 100x \> potent than morphine Lacks OH in phenol but still lipophilic

Question 50

Which methadone isomer is active?

Question 51

Where is methadone's chiral centre?

Question 52

What is the clinical use of methadone?

Question 53

Why is methadone marketed in its racemic form?

Question 54

What is the clinical use of methadone's S(+) isomer + how does this lead to its serious side effects?

Question 55

Methadone has a prolonged duration of action. Why is this?

Question 56

How is methadone administrated?

Answer 56

Orally or Injection

Question 57

A patient has difficulty swallowing orally. How can they be administered methadone?

Answer 57

Swish + spit Patients who struggle swallowing oral dosage forms use methadone with alkalinising agent to increase saliva pH from 6.4 - 8.5 If solution is held in mouth for 2 and a half minutes, buccal absorption of 85% is achieved

Question 58

What opioid receptor does tramadol use?

Question 59

Who cannot take tramadol + why?

Question 60

What racemic isomer form is tramadol marketed + why?

Answer 60

Racemic mixture of Cis-Isomers (1R, 2R) enantiomer \> 30x potent than (1S, 2S) Racemic formulation displays tolerability

Question 61

Describe tramadol metabolism

Answer 61

O-demethylated via CYP2D6 metabolism to more potent opioid (200 fold increase)

Question 62

How are oripavines made?

Question 63

What are conformational restrictions?

Question 64

What is the diers-alders reaction?

Answer 64

Concerted cycloaddition reaction between diene + dienophile to form 6-membered ring containing double bond

Question 65

How are oripavines formed?

Question 66

Examples of oripavines

Question 67

How was buprenorphine made?

Question 68

How is buprenorphine formulated?

Question 69

Difference between Etorphine + Morphine

Question 70

Clinical use of Etorphine