Management of Musculoskeletal Pain and Inflammation

Question 1

What is the main mode of action of NSAIDs therapeutic effect?

1 - inhibition of COX-1
2 - inhibition of COX-2
3 - inhibition of COX-3
4 - inhibition of miu-opioid receptor
5 - Inhibition of transcriptions of inflammatory genes

Answer 1

2 - inhibition of COX-2

Question 2

What is the main cause of NSAIDs gastric adverse reactions?

1 - Inhibition of COX-1
2 - Inhibition of COX-2
3 - Inhibition of COX-3
4 - Inhibition of miu-opioid receptor
5 - Inhibition of transcriptions of inflammatory genes

Answer 2

1 - Inhibition of COX-1

- COX-1 is helpful in producing gastric juice

Question 3

What effect do prostaglandins have on the afferent arteriole (kidney/glomerulus)?

1 - No effect
2 - Occlusion
3 - Vasoconstriction
4 - Vasodilation
5 - Vasospasm

Answer 3

4 - Vasodilation

Question 4

What are the 3 key core drugs we need to know that come under NSAID category?

1 - aspirin, atorvastatin, naproxen
2 - aspirin, paracetamol, naproxen
3 - aspirin, ibuprofen, naproxen
4 - paracetamol, ibuprofen, aspirin

Answer 4

3 - aspirin, ibuprofen, naproxen

Question 5

Are paracetamols classed as an NSAIDs?

Answer 5

• no

Question 6

Which pathway are NSAIDs ultimately trying to inhibit?

Answer 6

• cyclooxygenase pathway

Question 7

Do NSAIDs mainly work centrally or peripherally?

Answer 7

• peripherally reducing prostaglandins

Question 8

In a direct response to prostaglandins there is an increased pain sensation at the nocioceptors. An influx of what 2 cations is the cause of this increased pain sensation?

1 - Mg+ and Ca2+
2 - Na+ and Cl-
3 - Na+ and K+
4 - Na+ and Ca2+

Answer 8

4 - Na+ and Ca2+

Question 9

Aspirin has its affect through an irreversible binding. What is the mechanism of action or aspirin?

Answer 9

• inhibits cyclooxygenase

Question 10

What are the most common side effects of aspirins?

Answer 10

• tinnitus
• reyes syndrome (swelling in the liver and brain)
• asthma

Question 11

Out of COX-1 and COX-2, which is pro-inflammatory and which is protective and function and maintenance of tissues?

Answer 11

• COX-I = protective and function and maintenance of tissues

- COX-II = pro-inflammatory

Question 12

COX-I and COX-II has a number of adverse effects. What are the 3 key adverse effects of inhibiting COX-I and II?

Answer 12

1 - peptic ulcers
2 - renal failure
3 - fluid retention and heart failure

Question 13

Prostaglandins can cause problems if there is too much as we seen in inflammatory conditions. What 2 positive effects to prostaglandin, specifically E2 and I2 have on the stomach?

Answer 13

1 - increased gastric acid secretion
2 - increased mucus production
- TOO MUCH NSAIDS WILL STOP BOTH OF THE ABOVE AND CAUSE PEPTIC ULCERS

Question 14

What can be taken alongside chronic NSAIDs to reduce stomach symptoms?

Answer 14

• proton pump inhibitors

Question 15

How do NSAIDs lead to renal problems?

Answer 15

• prostaglandins are vasodilators and increase afferent blood flow to kidneys
• NSAIDs inhibit prostaglandins and reduce blood flow causing acute kidney disease

Question 16

How can NSAIDs lead to water and Na+ retention?

Answer 16

• reduced blood flow means reduced filtration of water and Na+

Question 17

Selective COX-2 inhibitors all have what letters at the end of their names?

Answer 17

• all end in coxib

- core drug is etoricoxib (binds and inhibits COX-II)

Question 18

What are the 3 main effects of NSAIDs?

Answer 18

1 - analgesic
2 - anti-inflammatory
3 - antipyretic

Question 19

What are the 3 key adverse events of selective COX-2 inhibitors?

Answer 19

• fertility issues
• CVD
• prothrombin (inhibits clotting, whilst increasing blood flow)

Question 20

What is the main organ/system affected paracetamol toxicity?

1 - Brain
2 - Heart
3 - Kidney
4 - Liver
5 -Lungs

Answer 20

4 - Liver

Question 21

Paracetamol is directly toxic to the liver, and can lead to liver failure (hepatic necrosis) in overdose.

1 - True
2 - False

Answer 21

• false

- paracetamol creates a compound and this is toxic, not paracetamol

Question 22

Does paracetamol perform the same 3 functions as NSAIDs?

Answer 22

• no
• only analgesic and antipyretic
• NOT ANTI-INFLAMMATORY

Question 23

Does paracetamol work mainly on the central or peripheral nervous system?

Answer 23

• centrally

Question 24

What organ metabolises paracetamol?

1 - heart
2 - liver
3 - kidney
4 - pancreas

Answer 24

2 - liver

Question 25

Paracetamol is metabolised in the liver and generally is excreted by the kidneys. However, there is a small portion of paracetamol that is metabolised by the enzyme cytochrome P450. This metabolism then leads to a very toxic compound called what? 1 - glucuronidation 2 - N-acetyl-p-benzoquinone imine (NAPQI) 3 - sulfation 4 - CYP450

Answer 25

2 - N-acetyl-p-benzoquinone imine (NAPQI)

Question 26

Paracetamol is metabolised in the liver and generally is excreted by the kidneys. However, there is a small portion of paracetamol that is metabolised by the enzyme cytochrome P450. This metabolism then leads to a very toxic compound called N-acetyl-p-benzoquinone imine or NAPQI. At normal levels of paracetamol there is an enzyme in the liver that is able to neutralise NAPQI. What is this enzyme called? 1 - glutathione 2 - phenyotoin 3 - sulfation 4 - CYP450

Answer 26

1 - glutathione

Question 27

Paracetamol is metabolised in the liver and generally is excreted by the kidneys. However, there is a small portion of paracetamol that is metabolised by the enzyme cytochrome P450. This metabolism then leads to a very toxic compound called N-acetyl-p-benzoquinone imine or NAPQI. At normal levels of paracetamol there is an enzyme in the liver that is able to neutralise NAPQI, called glutathione. What can happen if a patient takes too much paracetamol and how can this become toxic?

Answer 27

- lots of paracetamol needs metabolising, meaning more NAPQI will be produced - hepatocytes are unable to produce sufficient glutathione to neutralise NAPQI - NAPQI then damages the liver and can cause liver failure

Question 28

Overdose of paracetamol leads to excessive levels of NAPQI in the liver, which is very toxic and can cause liver failure. What can patients be give to treat this? 1 - metformin 2 - atorvastatin 3 - antibiotic 4 - N-acetylcysteine (intravenously)

Answer 28

- N-acetylcysteine (intravenously) | - precursor of glutathione, so will neutralise NAPQI

Question 29

What is the treatment for paracetamol overdose?

Answer 29

- N-acetylcysteine (IV) | - glutathione precursor that neutralises NAPQI

Question 30

The therapeutic actions of corticosteroids are achieved in majority by which type of receptor? ``` 1 - Cytoplasmic / Nuclear 2 - Enzyme-linked receptor 3 - G-protein coupled receptor 4 - Ionotropic 5 - Tyrosine-kinase receptor ```

Answer 30

1 - Cytoplasmic / Nuclear - steroids can cross plasma membrane and enter cells - then bind with glucocorticoid receptor inside cell creating a complex - this complex can then enter nucleus and bind with DNA and change DNA transcription

Question 31

The main corticosteroids adverse reactions are predictable. 1 -True 2 - False

Answer 31

1 -True | - we know the effects and adverse effects of too much glucocorticoids so we can predict the drugs effects

Question 32

When prescribing corticosteroids for longer than a few days, is important to discuss with the patient a slow withdrawal of the drug. 1 - True 2 - False

Answer 32

1 - True - body could stop producing cortisol - can take a long time for the body to begin producing them again

Question 33

Corticosteroids given as medication mimic what in the body?

Answer 33

- glucocorticoids

Question 34

What are the 4 core drugs corticosteroids?

Answer 34

1 - Methylprednisolone 2 - Prednisolone 3 - Hydrocortisone 4 - Beclometasone

Question 35

Mechanism of action of corticosteroids?

Answer 35

- same effect that glucocorticoids have - down-regulate pro-inflammatory genes - able to inhibit phospholipase A2 and inhibit arachidonic acid, so also COX-I and II

Question 36

Why is abrupt removal of corticosteroids dangerous?

Answer 36

- can take time for body to produce corticosteroids again so van be dangerous

Question 37

Immune cells are able to utilise an enzyme called phospholipase A2 and get it to act on membrane phospholipids in order to create a 20 carbon poly-unsaturated fatty acid called what? 1 - cyclooxygenase 2 - arachidonic acid 3 - C reactive protein 4 - lactate dehydrogenase

Answer 37

2 - arachidonic acid

Question 38

Immune cells are able to utilise an enzyme called phospholipase A2 and get it to act on membrane phospholipids in order to create a 20 carbon poly-unsaturated fatty acid called arachidonic acid (AA). The AA provides a substrate for cyclooxygenase. What 2 things can this then go on to create?

Answer 38

- COX-I | - COX-II

Question 39

Immune cells are able to utilise an enzyme called phospholipase A2 and get it to act on membrane phospholipids in order to create a 20 carbon poly-unsaturated fatty acid called arachidonic acid (AA). The AA provides a substrate for cyclooxygenase. creating COX-I and II. COX-II and I can the produce 3 things, what are they? 1 - prostaglandins, TNF-a, prostacyclin 2 - prostaglandins, prostacyclin, thromboxane 3 - prostaglandins, IL-6, prostacyclin 4 - prostaglandins, thromboxane, IL-1

Answer 39

2 - prostaglandins, prostacyclin, thromboxane

Question 40

What do the terms inducible and constitutive refer to?

Answer 40

- inducible = molecule needs to be activates (COX-II) | - constitutive = molecule is always switched on (COX-I)