Management of Musculoskeletal Pain and Inflammation Flashcards
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
2 - inhibition of COX-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
1 - Inhibition of COX-1
- COX-1 is helpful in producing gastric juice
What effect do prostaglandins have on the afferent arteriole (kidney/glomerulus)?
1 - No effect 2 - Occlusion 3 - Vasoconstriction 4 - Vasodilation 5 - Vasospasm
4 - Vasodilation
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
3 - aspirin, ibuprofen, naproxen
Are paracetamols classed as an NSAIDs?
- no
Which pathway are NSAIDs ultimately trying to inhibit?
- cyclooxygenase pathway
Do NSAIDs mainly work centrally or peripherally?
- peripherally reducing prostaglandins
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+
4 - Na+ and Ca2+
Aspirin has its affect through an irreversible binding. What is the mechanism of action or aspirin?
- inhibits cyclooxygenase
What are the most common side effects of aspirins?
- tinnitus
- reyes syndrome (swelling in the liver and brain)
- asthma
Out of COX-1 and COX-2, which is pro-inflammatory and which is protective and function and maintenance of tissues?
- COX-I = protective and function and maintenance of tissues
- COX-II = pro-inflammatory
COX-I and COX-II has a number of adverse effects. What are the 3 key adverse effects of inhibiting COX-I and II?
1 - peptic ulcers
2 - renal failure
3 - fluid retention and heart failure
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?
1 - increased gastric acid secretion
2 - increased mucus production
- TOO MUCH NSAIDS WILL STOP BOTH OF THE ABOVE AND CAUSE PEPTIC ULCERS
What can be taken alongside chronic NSAIDs to reduce stomach symptoms?
- proton pump inhibitors
How do NSAIDs lead to renal problems?
- prostaglandins are vasodilators and increase afferent blood flow to kidneys
- NSAIDs inhibit prostaglandins and reduce blood flow causing acute kidney disease
How can NSAIDs lead to water and Na+ retention?
- reduced blood flow means reduced filtration of water and Na+
Selective COX-2 inhibitors all have what letters at the end of their names?
- all end in coxib
- core drug is etoricoxib (binds and inhibits COX-II)
What are the 3 main effects of NSAIDs?
1 - analgesic
2 - anti-inflammatory
3 - antipyretic
What are the 3 key adverse events of selective COX-2 inhibitors?
- fertility issues
- CVD
- prothrombin (inhibits clotting, whilst increasing blood flow)
What is the main organ/system affected paracetamol toxicity?
1 - Brain 2 - Heart 3 - Kidney 4 - Liver 5 -Lungs
4 - Liver
Paracetamol is directly toxic to the liver, and can lead to liver failure (hepatic necrosis) in overdose.
1 - True
2 - False
- false
- paracetamol creates a compound and this is toxic, not paracetamol
Does paracetamol perform the same 3 functions as NSAIDs?
- no
- only analgesic and antipyretic
- NOT ANTI-INFLAMMATORY
Does paracetamol work mainly on the central or peripheral nervous system?
- centrally
What organ metabolises paracetamol?
1 - heart
2 - liver
3 - kidney
4 - pancreas
2 - liver
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
2 - N-acetyl-p-benzoquinone imine (NAPQI)
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
1 - glutathione
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?
- 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
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)
- N-acetylcysteine (intravenously)
- precursor of glutathione, so will neutralise NAPQI
What is the treatment for paracetamol overdose?
- N-acetylcysteine (IV)
- glutathione precursor that neutralises NAPQI
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
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
The main corticosteroids adverse reactions are predictable.
1 -True
2 - False
1 -True
- we know the effects and adverse effects of too much glucocorticoids so we can predict the drugs effects
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
1 - True
- body could stop producing cortisol
- can take a long time for the body to begin producing them again
Corticosteroids given as medication mimic what in the body?
- glucocorticoids
What are the 4 core drugs corticosteroids?
1 - Methylprednisolone
2 - Prednisolone
3 - Hydrocortisone
4 - Beclometasone
Mechanism of action of corticosteroids?
- 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
Why is abrupt removal of corticosteroids dangerous?
- can take time for body to produce corticosteroids again so van be dangerous
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
2 - arachidonic acid
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?
- COX-I
- COX-II
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
2 - prostaglandins, prostacyclin, thromboxane
What do the terms inducible and constitutive refer to?
- inducible = molecule needs to be activates (COX-II)
- constitutive = molecule is always switched on (COX-I)