NSAIDs Flashcards

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1
Q

Where is Arachidonic acid primarily derived from?

A

Dietary linoleic acid (vegetable oils converted hepatically to Arachidonic acid and incorporated into phospholipid membrane)

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2
Q

Arachidonic acid is found throughout the body, but in what in what 4 tissues/ organs mainly?

A
  • Brain
  • Muscle
  • Liver
  • Kidney
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3
Q

List 3 types of Prostanoids

A
  • Prostaglandins
  • Prostacyclins (E.g PGI2)
  • Thromboxanes
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4
Q

Describe the production of Prostanoids

A
  • Produced from Arachidonic acid via Cyclooxygenase pathways
  • Produced locally on demand via different enzymes
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5
Q

What feature of Prostanoids allows their concentration to be finely controlled?

A

Short half lives

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6
Q

How do TXA2 and PGI2’s effects differ?

A

PGI2- Protective for CVS
TXA2- Bad for CVS (causes platelet aggregation and vasodilation)

Fine balance needed between them

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7
Q

Which Prostanoids are good for the stomach and how?

A

PGE2: Regulates acid secretion from Parietal cells

PGI2: Maintains blood flow and mucosal repair

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8
Q

Do Prostanoids act through GPCRs?

A

Yes

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9
Q

A diet rich in what can lead to conversion of TXA3 and PGI3 (healthier prostanoids) reducing CVD incidence?

A

Fish oils/ Omega fatty acids

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10
Q

Compare 2 functional isomers of COX enzymes

A

COX-1;
- Always active in most tissues

COX-2;

  • Inducible (mostly) in chronic inflammation
  • Always active in Brain + Kidney + Bone

(Possibly COX-3)

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11
Q

How do NSAIDs work?

A

Inhibition of COX by competing with Arachidonic acid

Thus reducing synthesis of Prostanoids

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12
Q

How do NSAIDs act as analgesics?

A

Inhibition of Prostaglandin synthesis reduced pain fibre sensitivity

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13
Q

How do NSAIDs act as anti-inflammatory agents

A

Reduces prostaglandin production-> Reduced vasodilation and oedema

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14
Q

List 4 ADRS of NSAIDs

A
  • GI irritation & bleeding (peptic ulcers, perforation)
  • Exacerbation of IBD
  • Reversible drop in GFR and Renal Blood Flow
  • Increased Na absorption-> Raised BP
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15
Q

List some DDIs of NSAIDs

A

Can all increase GI irritation, so may have to give a PPI;

  • Aspirin
  • Glucocorticoid steroids
  • Anticoagulants
  • ACEi, ARB, Diuretics
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16
Q

List some contraindications of NSAIDs

A
  • Eldery
  • Chronic use
  • Smoking & alcohol
  • History of peptic ulcers
  • Helicobacter pylori
  • CKD, Heart failure
17
Q

How can NSAIDs taken with ARBs/ ACEi/ Diuretics affect the kidney?

A

NSAIDs: Inhibit Afferent Arteriole vasodilation

ARB/ ACEi/ Diuretics: Inhibit Efferent Arteriole vasoconstriction

Thus, reduced GFR-> possible Renal impairment

18
Q

What class of drug are Celecoxib and Etoricoxib?

What brought about the creation of this class of drugs?

A

Selective COX-2 inhibitors

GI side effects of COX-1 inhibitors

19
Q

Compare the effects of COX-1 and COX-2 inhibitors

A

COX-1;

  • More GI ADRs
  • Antiplatelet action-> Inhibit platelet aggregation

COX-2;

  • Less GI ADRs, similar renal ADRs
  • Promote platelet aggregation (via PGI2 inhibition)
20
Q

What feature of COX-2 inhibitors may allow them to be used in the long-term treatment of patients with severe Osteo- and Rheumatoid arthritis?

(Still need to be monitored)

A

Reduced GI effects

21
Q

Which NSAIDs increase risk of MI?

A

All

22
Q

Describe the effect of NSAIDs on other protein-bound drugs

Name 3 highly protein bound drugs that can be affected by NSAIDs

A

NSAIDs act strongly to displace protein-bound drugs increasing the free drug concentration in plasma.

Can displace protein-bound;

  • Warfarin
  • Methotrexate
  • Sulphonylureas drugs
23
Q

Why is Paracetamol unique?

A

A non-NSAID, non-Opiate with Antipyretic and Analgesic action

(For mild-moderate analgesia and fever)

24
Q

Does Paracetamol have any anti-inflammatory action?

A

Very little

25
Q

How much Paracetamol needs to be taken to cause irreversible damage?

A

150mg/kg

26
Q

Describe the course of Paracetamol Overdose

A
  • Can be asymptomatic for many hours
  • First 24h: Nausea, Vomiting, Ab pain
  • At 3-4 days: Maximal liver damage occurs
27
Q

What can be taken to combat a very recent paracetamol OD?

A

Activated charcoal (would also counter any other drugs the patient is on)