Pharmacology of Pain

Question 1

What is paracetamol (acetaminophen) used for?

Answer 1

• Acetaminophen is an analgesic drug used alone or in combination with opioids for pain management (including GORD / Peptic Ulcer Disease), and as an antipyretic agent
  
  • Not an NSAID → little anti-inflammatory activity

Question 2

What is the primary drug target of paracetamol (acetaminophen)?

Answer 2

• Not well defined. Possible targets:
  
  • 5HT3 receptors
  • Cannabinoid reuptake proteins
  • Peroxidase

Question 3

What is the drug target type of paracetamol (acetaminophen)?

Answer 3

• Probably inhibitor / antagonist

Question 4

What is the primary mechanism of action of paracetamol (acetaminophen) (5)?

Answer 4

• Not entirely clear
• Inhibits peroxidase enzyme (which converts arachidonic acid to prostaglandins involving cyclooxygenase enzyme)
• Peroxidase inhibition can be blocked with excessive levels of peroxidase build (e.g. inflammation)
• Activation of descending serotonergic pathways (possibly vis 5HT3)
• Inhibits reuptake of endogenous endocannabinoid (which increases cannabinoid receptor activation); may contribute to activation of descending pathways

Question 5

What is the location of action of paracetamol (acetaminophen)?

Answer 5

• Peripheral & Central Nervous System

Question 6

What are the main adverse effects of paracetamol (acetaminophen)(2)?

Answer 6

• Rare: Allergic skin reaction
• In case of overdose: Hepatotoxicity

Question 7

What are the symptoms of of paracetamol overdose (common method of suicide) (3)?

Answer 7

• Nausea
• Vomiting
• Onset of right subcostal pain after 24 hours indicate hepatic necrosis

Question 8

How is paracetamol overdose (common method of suicide) managed?

Answer 8

• < 8 hours: Activated charcoal + Acetylsteine + Antiemetic
• 8 - 24 hours: Acetylsteine + Antiemetic
• > 24 hours: Acetylsteine + Antiemetic

Question 9

What are opioids used for?

Answer 9

• Opioids are used for the relief of moderate to severe acute and chronic pain

Question 10

What is the primary drug target of opioids?

Answer 10

• Opiod receptor

Question 11

What is the drug target type of opioids?

Answer 11

• Receptor agonist

Question 12

What is the location of action of opioids?

Answer 12

• Central Nervous System (CNS)

Question 13

What is the mechanism of action of opioids?

Answer 13

• 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 of pain.
• Antitussive effect (cough supressant) due to decreased activation of afferent nerves relaying cough stimulus from airway to brain.

Question 14

What are the main adverse effects of opioids (3)?

Answer 14

• Nausea (Increased activity in chemoreceptor trigger zone)
• Vomiting (Increased activity in chemoreceptor trigger zone)
• Constipation (Opioid receptor in GIT can reduce gut mobility)

Question 15

Give 2 examples of weak opioids.

Answer 15

• Codeine
• Tramadol

Question 16

Give 3 examples of strong opioids.

Answer 16

• Morphine
• Fentanyl
• Diamorphine (Heroin)

Question 17

What are the symptoms of opioid overdose?

Answer 17

• Respiratory depression (Direct & Indirect inhibition of respiratory control centre)

Question 18

What is the management of opioid overdose?

Answer 18

• Ventilation
• Naloxone

Question 19

What is co-amoxiclav a combination of?

Answer 19

• Amoxicillin
• Clavulanic acid

Question 20

What is amoxicillin used for?

Answer 20

• Amoxicillin is a penicillin derivative used for the treatment of infections caused by gram-positive bacteria, in particular streptococcal bacteria causing upper respiratory tract infections

Question 21

What is clavulanic acid used for?

Answer 21

Clavulanic acid is a beta lactamase inhibitor used to enhance the effectiveness of beta lactam antibiotics

Question 22

What is the primary drug target of amoxicillin?

Answer 22

• Penicillin binding proteins

Question 23

What is the primary drug target of clavulanic acid?

Answer 23

• Beta-lactamase

Question 24

What is the drug target type of amoxicillin?

Answer 24

• Protein inhibitor

Question 25

What is the drug target type of clavulanic acid?

Answer 25

• Enzyme inhibitor

Question 26

What is the location of action of amoxicillin?

Answer 26

• Bacteria

Question 27

What is the location of action of clavulanic acid?

Answer 27

• Bacteria

Question 28

What is the mechanism of action of amoxicillin?

Answer 28

• Amoxicillin binds to bacterial penicillin binding proteins
• This prevents transpeptidation (the cross-linking process for bacterial cell wall synthesis

Question 29

What is the mechanism of action of clavulanic acid?

Answer 29

• Clavulamate is an inhibitor of beta lactamase
  
  • Beta lactamase is a bacterial enzyme that can degrade beta lactam antibiotics and thus confer resistanse to these antibiotics

Question 30

What are the main adverse effects of co-amoxiclav (2)?

Answer 30

• Nausea
• Vomiting

Question 31

What is lactulose used for?

Answer 31

• Lactulose is a disaccharide derivative of lactose used to treat constipation, portal systemic encephalopathy and pain

Question 32

What is the primary drug target of lactulose?

Answer 32

• No primary drug target

Question 33

What is the drug target type of lactulose?

Answer 33

• No drug target type

Question 34

What is the location of action of lactulose?

Answer 34

• Large bowel

Question 35

What is the mechanism of action of lactulose?

Answer 35

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

Question 36

What are the main adverse effects of lactulose (4)?

Answer 36

• Abdominal pain
• Diarrhoea
• Flatulence
• Nausea