Pharmacology of Pain

Question 1

What are some weak opioids?

Answer 1

codeine, tramadol

Question 2

What are some strong opioids?

Answer 2

morphine, fentanyl, (heroin)

Question 3

What is the mechanism of action for opioids?

Answer 3

Over-arching mechanism at a cellular level is a depressant effect on cellular activity. Multiple sites within pain pathway, where activation of the opioid receptor leads to decreased perception or increased tolerance to pain.

Question 4

Why is there an Anti-tussive effect to opioids?

Answer 4

Anti-tussive effect due to decreased activation of afferent nerves relaying cough stimulus from airways to brain



Question 5

What is the primary target for Opioids?

Answer 5

opioid receptor

Question 6

What are the mild side effects of opioids?

Answer 6

nausea & vomiting (increase activity in chemoreceptor trigger zone) and constipation (opioid receptors in GIT can reduce gut motility)

Question 7

What are the symptoms of opioid overdose?

Answer 7

respiratory depression (direct and indirect inhibition of respiratory control centre.)



Question 8

What is the mechanism of action of Co-amoxiclav?

Answer 8

Amoxicillin (like all penicillin like drugs) binds to bacterial penicillin binding proteins. This prevents transpeptidation (the cross linking process for bacterial cell wall synthesis)

Clavulanate is an inhibitor of beta lactamase. Beta lactamase is a bacterial enzyme that can degrade beta lactam anti-biotics and thus confer resistance to these anti-biotics.



Question 9

What is the primary target site for Co-amoxiclav?

Answer 9

Amoxicillin = penicillin binding proteins

Clavulanate = beta lactamase



Question 10

What are the side effects of Co-amoxiclav?

Answer 10

Amoxicillin is well tolerated. Most common side effects are nausea and diarrhoea.

Question 11

Describe Amoxicillin

Answer 11

Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms



Question 12

What happens in hypersensitivity to penicillin?

Answer 12

Hypersensitivity to penicillins is relatively common. Usually associated with rash but can lead to anaphylactic reactions.

Question 13

Where is Co-amoxiclav commonly prescribed?

Answer 13

hospital settings

Question 14

What is the mechanism of action of Lactulose?

Answer 14

actulose is a non-absorbable disaccharide. It reaches the large bowel unchanged. This causes water retention via osmosis and an easier to pass stool. It can also be metabolised by colonic bacteria. The colonic metabolism of sugars has an additional laxative effect.

Question 15

What is the primary target of Lactulose?

Answer 15

No drug target

Question 16

What are the side effects of Lactulose?

Answer 16

Abdominal pain, diarrhoea, flatulence, nausea.

Question 17

How quickly does Lactulose begin working?

Answer 17

Begins working within 8-12 hours but may take up to 2 days to improve constipation.



Question 18

What is Lactulose’s effect on constipation?

Answer 18

Constipation is a very common side effect of opioids. Lactulose is often prescribed prior to commencement of opioid therapy to improve symptoms associated with constipation.

Question 19

What is given for mild pain?

Answer 19

Nonopioid +/- adjuvant therapy

Question 20

What is given for mild to moderate pain?

Answer 20

weak opioid +/- nonopioid +/- adjuvant therapy

Question 21

What is given for moderate to severe pain?

Answer 21

Strong opioid +/- nonopijoid therapy +/- adjuvant therapy

Question 22

What determines a drugs ability to get to the brain?

Answer 22

Lipid solubility as the major route for drug permeation to the brain is via passive diffusion

Question 23

What is the effect of opioids at the pre-synaptic neurone?

Answer 23

inhibit ATP to cAMP conversion

inhibit calcium influx

enhance potassium reflux

Question 24

What are the effects of morphine and naloxone on opioid receptors?

Answer 24

Morphine is an opioid receptor agonist. Naloxone is an opioid receptor antagonist. Agonists possess affinity and efficacy for a receptor. Antagonists only possess affinity for a receptor.

Question 25

What is the relationship between morphine and codeine?

Answer 25

codeine is primarily a pro-drug for morphine. As you can see in the figure below, codeine can be metabolized to both norcodeine (inactive metabolite) AND morphine (active metabolite). In the liver, cytochrome P450 enzymes are responsible for this metabolism. CYP3A4 is responsible for ‘fast’ metabolism of codeine to norcodeine and CYP2A6 is responsible for ‘slow’ metabolism of codeine to morphine