Peripheral and central analgesia

Question 1

List 5 methods of pain relief

Answer 1

Remove peripheral stimulus
Interrupt nociceptive input
stimulate nociceptive inhibitory mechanisms
Modulate central appreciation of pain
Block or remove secondary factors maintaining pain

Question 2

What substances are released to activates nociceptors?

Answer 2

Algogenic substances

Question 3

What 2 algogenic substances can be exploited by analgesics?

Answer 3

Substance P

Prostaglandins

Question 4

Other than activate nociceptive pathways, what is the function of the release of allogenic substances?

Answer 4

Activate inflammatory cascade

Question 5

What cascade do analgesics tens to target?

Answer 5

Inflammatory cascade through inhibition of algogenic substances at or near the site of injury

Question 6

List 2 types of analgesics commonly used

Answer 6

Paracetamol
NSAIDs
COX-2 inhibitors

Question 7

How is paracetamol an anti-pyretic?

Answer 7

Prostaglandin inhibition in hypothalamus

Question 8

Is paracetamol an anti-inflammatory?

Answer 8

No

Question 9

In what type of patients should paracetamol should be avoided?

Answer 9

Patients with pre-existant liver disease

Question 10

Where is paracetamol metabolised?

Answer 10

liver

Question 11

How can paracetamol be harmful for people with pre-existant liver disease?

Answer 11

10% of paracetamol is metabolised via conjugation to NAPQI
This is hepatotoxic
It is normally inactivated by glutathione, but in people with liver disease glutathione is reduced/non-existant, so NAPQI build up causing liver cell death

Question 12

How is paracetamol normally metabolised?

Answer 12

In the liver, 90% into a harmless product and excreted, 10% via conjugation to NAPQI, a hepatotoxic compound, normally inactivated by glutathione into a safe compound that can be excreted

Question 13

What are the immediate clinical manifestations of paracetamol overdose?

Answer 13

No immediate manifestations

Question 14

What should you do if a patient coming in complaint about dental pain says they have taken more than the recommended dose of paracetamol?

Answer 14

Dental problem should take a back seat and they should be taken to A&E

Question 15

What are the risk factors for paracetamol overdose?

Answer 15

Liver disease e.g. less glutathione

Alcohol abuse, malnourished

Question 16

How can paracetamol be treated?

Answer 16

Activated charcoal (absorbs excess paracetamol in the system) and give them a precursor for glutathione to increase glutathione production

Question 17

Name 2 NSAIDs

Answer 17

Aspirin Ibuprofen

Question 18

Generally, how do NSAIDs work?

Answer 18

Non-selective block of cyclo-oxygenase (COX) enzyme

Question 19

Name the 2 forms of COX that NSAIDs non-selectively inhibit

Answer 19

COX1 COX2

Question 20

Explain the role of COX1

Answer 20

Production of prostaglandins that help synthesis of gastric mucosal mucus and regulate gastric acid

Question 21

Explain the role of COX2

Answer 21

Helps the production of prostaglandins and other inflammatory mediators that cause acute pain

Question 22

List 4 beneficial effects of NSAIDs

Answer 22

Anti-pyretic
Analgesic
Anti-inflammatory
Anti-platelet (aspirin only)

Question 23

How do NSAIDs cause an anti-pyretic effect?

Answer 23

Inhibit prostaglandin production in the hypothalamus

Question 24

List 4 unwanted effects fo NSAIDs?

Answer 24

Gastric ulceration
Platelet effects
Induce asthmatic attacks
Non-selective COX inhibitor causes dysregulation of gastric acid and renal toxicity

Question 25

What is 'safe aspirin', why is it named so?

Answer 25

Selective COX-2 inhibitor, decreased gastric side-effects

Question 26

Disadvantages of safe aspirin?

Answer 26

Increased risk of MI

Question 27

Why should ibuprofen be taken with meals?

Answer 27

Better absorption in the stomach with food

Question 28

Name a centrally acting analgesic?

Answer 28

Opioids

Question 29

How are opioids classified?

Answer 29

Strength - weak = codeine, strong = morphine

Question 30

How do opioids work?

Answer 30

Pure or partial agonists to opioid receptors

Question 31

How is the strength of an opioid determined?

Answer 31

``` Strong = pure agonist at opioid receptor Intermediate = partial ```

Question 32

What are the side-effects of opioids?

Answer 32

Respiratory depression, depression, decrease gut mobility, dependence, nausea

Question 33

Describe the opioids mode of action?

Answer 33

Bind to opioid receptors centrally and peripherally This activates descending inhibitory control over nociception Also inhibits propagation of impulse though stopping neurotransmitter release peripherally

Question 34

When are opioids prescribes?

Answer 34

Pain is moderate to severe Pain has significant impact on function Pain has significant impact on quality of life Other treatments have been tried and failed Patient has consented to be closely monitored

Question 35

How quickly does dependence begin?

Answer 35

24 hours

Question 36

How does chronic exposure to opioids effect receptors?

Answer 36

Increase no. and sensitivity = increase cellular response

Question 37

What are the 4C's involved in additction?

Answer 37

Compulsive use Impaired control over use Continued use despite consequences Craving

Question 38

Where is morphine metabolised?

Answer 38

Hepatic and renal metabolism

Question 39

Why is morphine not effective given orally?

Answer 39

Extensive first pass metabolism