NSAIDS Flashcards

1
Q

What are the 3 major clinical uses of NSAIDS?

A

Analgesics
Antipyretics
Anti-inflammatories

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2
Q

From what are prostanoids derived, and where does this originate?

A

Arachdionic acid

Plasma membrane

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3
Q

Recall 2 key prostanoids

A

TXA2 (thromboxane A2)

PGI2 (prostacyclin)

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4
Q

What is the rate-limiting step in prostaglandin synthesis?

A

COX-driven conversion of arachdionic acid to endoperoxidases such as PGH2 and PGG2

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5
Q

Recall the 10 types of prostanoid receptor

A
DP1 DP2
EP1 EP2 EP3 EP4
FP
IP1 IP2
TP
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6
Q

What is PGE2?

A

Type of prostanoid

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7
Q

What receptors does PGE2 have affinity for?

A

EP1234

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8
Q

Recall a desirable action of PGE2

A

Neuroplasticity, bronchodilation, osmotic homeostasis, gastroprotection, vasoregulation

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9
Q

Summarise 4 unwanted effects of PGE2

A
  1. Enhanced pain perception
  2. Pyrogenic
  3. Acute inflammation
  4. Cancer risk increased
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10
Q

How does PGE2 lower the pain threshold?

A

Sensitises nocioreceptors

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11
Q

Why is PGE2 pyrogenic?

A

It stimulates hypothalamic neurons that initiate a rise in body temp

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12
Q

Recall the mechanism by which PGE2 regulates inflammation?

A

Moderated by:

  • EP3
  • Calcium
  • Multiple GPCRs
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13
Q

How does PGE2 increase risk of malignancy?

A

Inhibits apoptosis

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14
Q

Why is aspirin unique among the NSAIDS?

A

Selective for COX1

Binds IRreversible

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15
Q

Describe how aspirin reduces platelet aggregation

A

Platelets:
- produce TXA2 which increases aggregation
- cannot replenish COX1 as have no nucleus
Endothelium:
- Produces PGI2 which decreases aggregation
- are nucleated so can replenish COX1+2
Aspirin inhibits TXA2 production and it cannot be replaced, PGI2 synthesis is affected to a lesser extent

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16
Q

What is the main consequence of paracetamol overdose?

A

Irreversible liver failure

17
Q

Recall the metabolism of paracetamol

A

CYP450
Metabolite = NAPQI: toxic as oxidises thiol groups on key enzymes for cell survial
NAPQI usually mopped up by glutathione, but if this is depleted NAPQI accumulates

18
Q

What is the antidote to paracetamol overdose?

A

Acetylcysteine - it has thiol (SH) groups

19
Q

Recall the 4 main side effects of NSAID use

A

Loss of benefits of PGE2:

  1. Bronchoconstriction
  2. Renal toxicity
  3. Loss of PGE2 gastroprotectivity
  4. Vasoconstriction
20
Q

How do NSAIDS lead to bronchoconstriction?

A

Inhibit COX
COX inhibits leukotriene production
Leukotrienes are bronchoconstictors

21
Q

What is the effect of PGE2 on the kidney?

A

Increases renal blood flow

22
Q

How do NSAIDS cause renal toxicity?

A

Constrict afferent arteriole to reduce GFR

23
Q

What is the effect of PGE2 on the stomach?

A

Downregulates HCl
Stimulates mucous production
Stimulates HCO3- production

24
Q

What is the danger of NSAIDS to the stomach?

A

Increase risk of ulcers by inhibiting PGE2

25
Q

Give an example of a drug that inhibits both COX1 and COX2

A

Ibuprofen

26
Q

Give an example of a COX2 inhibitor

A

Celecoxib

27
Q

What is the benefit of having a drug that specifically inhibits COX2?

A

Avoids gastric ulcer risk

28
Q

What is the risk of having a drug that specifically inhibits COX2 as compared to aspirin?

A

CVD risk higher

29
Q

What is the main drawback of drugs that inhibit COX2 as well as COX2?

A

Significant side effect profile

30
Q

What can be coadministered with NSAIDS to offer gastroprotection?

A

PPI such as omeprazole

31
Q

Recall 2 contraindictions for NSAID use

A

Steroid use

Alcohol dependency