Pharmacology of pain

Question 1

Which drugs are used to treat pain?

Answer 1

Paracetamol
Opioids
Co-amoxiclav
Lactulose

Question 2

What is the drug target for paracetamol?

Answer 2

Unclear

• 5HT3 receptor
• Cannabinoid reuptake proteins
• Peroxidase

Question 3

What is the primary mechanism of action of paracetamol?

Answer 3

At peripheral sites, may inhibit a peroxidase enzyme which converts arachidonic acid to prostaglandins (1st step in this pathway involves the enzyme, cyclooxygenase). The ability of paracetamol to inhibit peroxidase can be blocked if excessive levels of peroxide build up (as is commonly seen in inflammation)

Activation of descending serotonergic pathways possibly via 5HT3 receptor activation

Inhibits reuptake of endogenous endocannabinoids, which would increase activation of cannabinoid receptors - this may contribute to activation of descending pathways



Question 4

What are the main side effects of paracetamol?

Answer 4

Relatively safe drug with few common side effects
OVERDOSE:
Liver damage and less frequently renal damage

Nausea and vomiting early features of poisoning (settle in 24h).
Onset of right subcostal pain after 24hindicates hepatic necrosis.

Question 5

What are examples of weak opioids?

Answer 5

Codeine

Tramadol

Question 6

What are examples of strong opioids?

Answer 6

Morphine, fentanyl

Question 7

What is the target of opioids?

Answer 7

Opioid receptor

Question 8

What is the primary mechanism of action of opioids?

Answer 8

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.

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

Question 9

What are the side effects of opioids?

Answer 9

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

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

Question 10

What is the drug target for co-amoxiclav?

Answer 10

Amoxicillin = penicillin binding proteins
Clavulanate = beta lactamase



Question 11

What is the primary mechanism of action of co-amoxiclav?

Answer 11

Amoxicillin 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 12

What are the side effects of co-amoxiclav?

Answer 12

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

Question 13

What is the drug target for lactulose?

Answer 13

No drug target

Question 14

What is the primary mechanism of action of lactulose?

Answer 14

Lactulose 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 are the side effects of lactulose?

Answer 15

Abdominal pain, diarrhoea, flatulence, nausea

Question 16

What are the 3 rungs of the WHO pain ladder?

Answer 16

• Mild pain
• Mild to moderate pain
• Moderate to severe pain

Question 17

What is the treatment of mild pain?

Answer 17

Non opioid with/without adjuvant therapy

Question 18

What is the treatment of mild to moderate pain?

Answer 18

Weak opioid
+/- nonopioid
+/- adjuvant therapy

Question 19

What is the treatment of moderate to severe pain?

Answer 19

Strong opioid
+/- non opioid
+/- adjuvant therapy

Question 20

What are the parts of the pain pathway?

Answer 20

Transduction
Transmission
Perception
Modulation

Question 21

Why are NSAIDS anti-inflammatory but Paracetamol is not?

Answer 21

NSAIDS stop the productions of prostaglandins. Prostaglandins normally cause sensory neurones to fire at a faster rate. Removing prostaglandins desensitises them

Paracetamol acts on the peroxidase which converts the PG intermediate to a PG

In a normal tissue with no inflammation you are going to have the prevention of PG synthesis with either Paracetamol and NSAIDs

The difference comes when we are the tissue is inflamed

Question 22

When is lactulose often prescribed?

Answer 22

prior to commencement of opioid therapy to improve symptoms associated with constipation

Question 23

How long does lactulose take to work?

Answer 23

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

Question 24

What type of AB is amoxicillin?

Answer 24

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