Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Inflammation > NSAIDS > Flashcards

NSAIDS Flashcards

1
Q

What activity does NSAIDS have?

A

Think the 3As:

Antipyretic (reduce fever)
Analgesic (pain relief)
At higher doses anti-inflammatory effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do NSAIDs work?

A

NSAIDs work by inhibiting the COX enzymes (COX-1 and COX-2). COX (cyclooxygenase) is a type of enzyme that acts in the phospholipid/arachidonic acid pathway initiated as a responsible to inflammation that faciliates the production of prostanoids, thromboxane, prostacyclin from arachidonic acid specifically.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe in full the arachidonic acid pathway.

A

When endotoxins are released by (gram negative) bacterium this causes damage to cell membranes which activates phospholipase A2 an enzyme which degrades phospholipids present within the cell membrane converting them to arachidonic acid. Arachidonic acid is then acted upon by two enzymes lipo-oxygenases which produces leukotrienes and cyclo-oxygenases. When either COX-1 or COX-2 acts on arachidonic acid converting it to two short-lived intermediates, PGG2 and PGH2. PGH2 is then metabolized to a variety of prostaglandins and related compounds collectively referred to as prostanoids; PGD2, PGE2, PGF2α, PGI2 and TXA2 (thromboxane).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do the COX enzymes convert arachidonic acid to the prostanoids?

A

They combine arachidonic acid (and some other unsaturated fatty acid) substrates with molecular oxygen to form unstable intermediates, cyclic endoperoxides, which can subsequently be transformed by other enzymes to different prostanoids.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the role of lipooxygenases?

A

Catalyse the oxygenation of polyunsaturated fatty acids such as arachidonic acid and linoleic acid to produce leukotrienes, lipoxins and other compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What leukotrienes are produced from lipo-oxygenases specifically in the arachidonic acid pathway?

A

Leukotriene B4, C4, D4 and E4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the crucial difference between COX-1 and COX-2?

A

COX-1 is a homeostatic regulator (responsible for inducing vascular responses and gastric acid secretion) and in most cells under normal physiological conditions. COX-2 however is only produced in response to inflammation and therefore a stronger drug target.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Aside for the production of COX-2 in inflammation, what cell types is it present in under normal physiological conditions?

A

CNS and renal tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which prostaglandins are produced by COX-1 and which by COX-2?

A

Whilst COX-1 and COX-2 have the same products (prostacyclin, prostaglandins and thromboxane) but they have different therapeutic effects depending on which enzyme and under what conditions they have been produced.
For example prostaglandins produced by COX-2 in response to inflammation causes pain, fever and inflammation but prostaglandins produced by COX-1 under normal physiological conditions has an effect on the GI tract, thrombocyte and kidney function and blood-flow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What prostaglandins are produced specifically from the COX/arachidonic acid pathway?

A

Prostaglandin D2, E2, F2a, I2 alongside prostacylin and thromboxane (TXA2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Would you want an NSAID to be COX-1 or COX-2 selective?

A

COX-2 selective as it is this enzyme specifically that is present in response to inflammation causing fever, pain and other therapeutic effects a patient would experience. Inhibition of COX-1 leads to a variety of side effects (GI).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are the different types of NSAIDs classified?

A

Dependent on how selective they are for COX-1 or COX-2.
Standard NSAIDs- non-selective for COX-1 or COX-2
COXIBS- COX-2 selective (still a slight affinity to COX-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are some examples of standard NSAIDS?

A

Ibuprofen
Aspirin
Indometacin
Mefenamic acid
Naproxen

Non-selective NSAIDS but a preference for COX-2:
Diclofenac
Etodolac
Meloxicam
Nabumetone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some examples of licensed COXIBS?

A

Celecoxib and Etoricoxib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What prostanoid dominates in inflammation?

A

Prostaglandin E2 but I2 also has an effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the functions of prostaglandin D2?

A

Vasodilation
Inhibits platelet aggregation
Relaxes GI and uterine muscle
Modification of release of hypothylamus and pituitary hormones
Chemo-attractants of leukocytes
Bronchoconstrictor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the functions of prostaglandin F2a?

A

Uterine contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the functions of prostaglandin I2?

A

Vasodilation
Inhibits platelet aggregation
Stimulates renin release
Natriuresis through its effects of tubular reabsorption of sodium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the functions of thromoxane A2?

A

Vasoconstriction
Platelet aggregation, bronchoconstriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the functions of prostaglandin E2 at EP1 receptors?

A

Contraction of the bronchial and gastro-intestinal smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the functions of prostaglandin E2 at EP2 and EP4 receptors?

A

Bronchodilation
Vasodilation
Stimulation of intestinal fluid secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the functions of prostaglandin E2 at EP3 receptors?

A

Contraction of the intestinal smooth muscle
Inhibits gastric acid secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do the production of the prostanoids differ in acute and chronic inflammation?

A

In acute inflammation prostaglandin E2 and I2 are generated by local tissues and blood vessels and prostaglandin D2 is released by mast cells.

In chronic inflammation monocytes/macrophages release prostaglandin E2 and TXA2 together. It is a ying yang effect in which prostanoids stimulate some responses and decrease others.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which two drugs which can be catorgrised as NSAIDs have a different pharmacological actions to the others?

A

Aspirin and paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Explain the anti-inflammatory action of NSAIDs.

A

Anti-inflammatory action is due to a decrease in prostaglandin E2 and prostacylin specifically which reduces vasodilation and oedema. However crucially NSAIDs do not have an effect on the accumulation of anti-inflammatory cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Explain the analgesic action of NSAIDs.

A

This is due to the reduced synthesis of prostaglandins meaning there is less sensitisation of nociceptive nerve ending specific to inflammatory mediators like bradykinin.
Reduced vasodilatory effect leading to relief of headache.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Explain the anti-pyretic effect of NSAIDs.

A

IL-1 releases prostaglandins into the CNS which elevates the hypothalamic set point for temperature control hence causing fever, NSAIDs prevent this.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the four indications of NSAIDs?

A

Antithrombotic
Analgesia
Anti-inflammatory
Anti-pyretic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

For each of the four indication of NSAIDs give example of the most appropriate drug to use.

A

Anti-thrombotic: only aspirin for risk of arterial thrombosis, other ones increase the risk of thrombosis

Analgesia:
Short-term - ibuprofen, paracetamol
Long-term- pivorixam, naproxen

Anti-inflammatory: ibuprofen, naproxen

Anti-pyretic: paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe the activity of paracetamol in application to ‘typical’ NSAID activity.

A

Analgesic and anti-pyretic activity but no significant anti-inflammatory activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What effect does paracetamol have on COX enzymes?

A

Although paracetamol is still a COX inhibitor this activity is restricted to the CNS COX enzymes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are some of the OTC interventions that have been made/can be made to prevent paracetamol overdosing.

A

Check for duplicate prescribing (appropriate counselling/restriction on a patient buying two compund preparations that contain paracetamol)

Limited packet size at 32, can sell up to 100 under pharmacist supervision

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How does the analgesic effect of paracetamol compare to that of an NSAID?

A

Same analgesic effect as a single dose NSAID

34
Q

In which patient groups does the dose of paracetamol need to be adjusted or monitored more closely?

A

Children
Low body weight
Hepatic impairment or patients with risk factors for hepatic impairment

35
Q

Do you need to adjust the oral or IV dose for special patient groups for paracetamol?

A

Both

For example, indicated for mild to moderate pain, IV

Adults up to 50kg - 15 mg/kg every 4–6 hours, dose to be administered over 15 minutes

Whereas adults over 50kg - 1g every 4–6 hours, dose to be administered over 15 minutes

36
Q

In what patients should paracetamol be considered the NSAID of choice?

A

Normally the first line choice when the patient has a co-morbidity or risk factor which increases their susceptibility of experiencing the side effects of other NSAIDs / other NSAIDs are contra-indicated, this includes:

Elderly
Patients with hypertension
Patients with CVD
Patients with renal impairment
Patients with GI issues
Patients on medications that interact with other NSAIDs (e.g Warfarin)

37
Q

What are the preparations paracetamol comes in?

A

Tablet
Capsule
Orodispersible tablet
Suspension
Suppositories
Infusions
Compound preparations- co-codamol, co-hydramol, Lemsip

38
Q

What is the typical dosing for paracetamol?

A

For adults: 0.5–1 g every 4–6 hours; maximum 4 g per day.

39
Q

Where does paracetamol undergo metabolism?

A

In the liver

40
Q

What is the half life of paracetamol?

A

2-4 hours

41
Q

What are the side effects a patient may experience if they consume a toxic dose of paracetamol?

A

Initially nausea and vomiting

After 24-48 hours causes fatal liver damage causing death

42
Q

Which drugs are administered if there are signs of paracetamol overdose?

A

Intravenous acetylcysteine or oral methionine which increase levels of glutathione preventing liver damage

43
Q

How does a paracetamol overdose cause liver damage?

A

When levels of glutathione become depleted, this means the toxic metabolite N-acetyl-p-benzoquinone imine begins to reacts with cellular proteins instead causing liver damage.

44
Q

What are the different doses of aspirin for its different indications?

A

Primary / Secondary prevention of CVD: 75mg - 300mg once daily (may need a loading dose - no analgesic/anti-inflammatory effect)

Analgesia: 300-900mg every four to six hours when required

45
Q

What is the maximum dose of aspirin daily?

A

4 grams

46
Q

Explain aspirin’s anti-platelet property.

A

Inhibits the thrombus formation in the arterioles. In fast moving blood vessels thrombi are composed of platelets with little fibrin.

47
Q

In which patient groups is aspirin contra-indicated?

A

Children under 16 due to Reye’s syndrome, post-viral encephalitis (swelling of the brain)
Previous or active peptic ulcerations (due to the side effects of aspirin)
Bleeding disorders (due to anti-platelet property)
Severe cardiac failure (exacerbate cardiac failure)
Previous hypersensitivity to aspirin or NSAID

48
Q

In which groups of patients is aspirin cautioned?

A

Elderly (increased risk of side effects such as renal, GI and bleeding)
Patients with asthma (risk of bronchospams)

49
Q

Which other drugs interact with aspirin?

A

Drugs that increase the risk of GI irritation/bleed:
Steroids, other NSAIDs, SSRIs, anti-coagulants Warfarin

Increased risk of renal side effects:
Bisphosphonates, Bendroflumethazide, monoclonal antibodies

Increased risk of toxicity (aspirin reduces the clearance):
Methotrexate

Check all cancer therapies with aspirin

50
Q

What preparations of aspirin are available?

A

Tablet
Enteric coated tablet
Dispersible tablet
Suppoistories
Compound preparations- Beechams powder

51
Q

Where is aspirin metabolised?

A

75% is metabolised in the liver

52
Q

What are some of the side effects associated with higher doses of aspirin?

A

Dizziness
Deafness
Tinnitus (‘salicylism’)
Compensatory respiratory alkalosis may occur

53
Q

What are some of the side effects associated with toxic doses of aspirin?

A

Uncompensated metabolic acidosis may occur, particularly in children

54
Q

When does are the therapeutic effects of NSAIDs felt?

A

The analgesic effect is felt soon after the first administration and the full effect is felt within a week.

The anti-inflammatory effect is normally after about three weeks

55
Q

If NSAID use is for an anti-inflammatory effect which drug is best?

A

The actual anti-inflammatory effect between the NSAIDs is minimal it is more likely for a drug to be prescribed based on the drug and patient characteristics.

56
Q

Compare side effects more prevalent with COXIBs in comparison to standard NSAIDs.

A

Less prevalent GI associated side effects but more prevalent cardiovascular associated side effects.

57
Q

What is the aim of NSAID therapy regarding the dose and duration?

A

Just like corticosteroid therapy the aim when an NSAID is indicated:

Lowest effective used for the shortest duration possible

58
Q

Explain the GI associated side effects with NSAID therapy.

A

There is COX-1 prostanoid inhibition which results in:
Reduced mucus production
Reduced bicarbonate production
Reduced mucosal blood flow

This leads to epithelial damage, ulceration and bleeding

59
Q

What interventions can be made to try and reduce the risk of developing GI associated side effects?

A

Lowest effective dose for the possible shortest duration
Highest incidence in the elderly
Does the patient already have any risk factors that make them increasingly susceptible to developing GI associated side effects (cautions and contra-indications)
Review need regularly
Advise to be taken with food
Co-prescribe with gastro-protection in those who are at risk of a bleed (PPI)
Encourage self monitoring
Review patient risk factors

60
Q

Which NSAIDs have the highest, intermediate and lowest GI associated risk ?

A

Highest risk - Piroxicam, Ketoprofen and Ketorolac

Intermediate - Indometacin, Diclofenac, Naproxen

Lower - Ibuprofen (up to 1.2g daily)

Lowest - COXIBS

61
Q

Which other drugs would further increase risk of GI toxicity?

A

Aspirin
Other NSAIDs

Others that increase risk of GI ulceration and bleed:
Steroids
Bisphosphonates

Increased risk of bleeding:
SSRIs
Anti-coagulants

62
Q

Which signs may you advise a patient to look out for regarding a GI toxicity?

A

Abdominal pain
Dyspepsia like symptoms
Haemoptysis
Dark or tarry stools

63
Q

Why is there an increased risk of cardiovascular events associated with NSAID use?

A

Due to the COX-2 inhibition impacting the vasculature, platelets and potential effects on the kidney.

64
Q

Can patients taking COXIBs still experience GI side effects?

A

Yes although the risk is lower than using standard NSAIDs, use of COX-2 inhibitors can still cause GI associated side effects.

65
Q

When is there an increased risk of thrombotic events associated with NSAID use?

A

Normally associated with longer duration and higher doses

66
Q

Which NSAIDs are associated with the highest and lowest risk of developing cardiovascular side effects?

A

Highest risk - COX-2 inhibitors, Diclofenac (dose of 150mg), Ibuprofen (daily dose of 2.4 grams)

Lower risk - Naproxen (1 gram daily)

67
Q

Does Ibuprofen with a daily dose of 1.2 grams have associated cardiovascular side effects?

A

No there is no evidence of increased cardiovascular risk of using 1.2 grams of Ibuprofen daily

68
Q

What are the key considerations that should be made in order to reduce the risk of a cardiovascular event associated with NSAID use?

A

NSAID selection (avoid COXIBs in patient with known other cardiovascular risk factors)
Ensure the lowest effective dose is used
Using NSAIDs for the shortest possible duration
Monitor the patient for adverse reactions
Reviewing the patient frequently for changes in risk factors

69
Q

What are some of the contraindications related to use of NSAIDs and cardiovascular disease?

A

COX-2 inhibitors (COXIBs), Diclofenac and high dose Ibuprofen are contra-indicated in:

Ischaemic heart disease
Cerebrovascular disease
Some stages of heart failure

Use of non-selective NSAIDs are cautioned in these patients and in those with known CVD risk factors

70
Q

Which cardiovascular drugs interact with NSAIDs?

A

Anti-hypertensives (NSAIDs increase blood pressure and therefore have a counter intuitive effect)

Anti-platelets such as Aspirin (NSAIDs reduce the effects of low dose Aspirin?)

71
Q

What are some of the cardiovascular monitoring parameters you would assess closely whilst a patient is taking NSAIDs?

A

Monitoring of cardiovascular risk factors:
Blood pressure
Cholesterol
Diabetes melluitis

Increased occurrence of cardiovascular events or first occurrence

72
Q

Explain the link between renal function and use of NSAIDs.

A

Both COX-1 and COX-2 play crucial roles in regulating kidney function. COX-1 controls glomerular filtration rate and renal hemodynamics whereas COX-2 aside from inflammation also functions to affect water and salt excretion. Inhibition of both of these enzymes therefore can cause different effects on the kidney and alter its function.

73
Q

Are all patients taking NSAIs at risk of developing renal side effects?

A

Most patients taking NSAIDs will not develop renal side effects, patients that are normotensive, do not have impaired renal function, are younger, will not develop these complications.

74
Q

Which patients are more likely to experience renal side effects from NSAID use?

A

Elderly
Renal impairment
Liver cirrhosis
Volume depletion
Heart failure

75
Q

Hence, which patient are contraindicated from NSAID use due to potential for renal side effects?

A

Those with the previously mentioned risk factors
Avoid in severe renal impairment and use in caution with milder impairment

76
Q

What are the key interactions regarding the potential for renal side effects in NSAIDs?

A

Nephrotoxic drugs - ACE inhibitors, diuretics
Anti-hypertensive medications
Lithium and Methotrexate (reduced clearance in renal impairment)

77
Q

What are some of the renal complications that can arise?

A

Acute kidney injury
Oedema
Hypertension due to increase water and sodium retention (link to heart failure and fluid build up)

78
Q

What are some of the monitoring parameters linked to renal function?

A

Renal function - eGFR, urea, urine output
Blood pressure
Electrolytes
Oedema

79
Q

What are some of the other potential side effects associated with NSAID use?

A

Bronchospams (occurs in 10%) therefore use in caution in asthmatics
Topical application leads to increased absorption in comparison to systemic use

80
Q

What is a key over the counter interaction of NSAIDs?

A

Patients who are on anti-coagulation therapy must not be self medicating with NSAIDs, only under direct supervision of clinician

81
Q

What are the key counselling points for somebody on NSAID therapy?

A

Do not self medicate with other NSAIDs
Use lowest effective dose for the shortest duration
Take with or after food
Self monitoring for GI disturbances

Inflammation (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions