15 NSAIDs Flashcards

1
Q

What are prostanoids and what do they do?

A

Prostanoids= a type of eicosanoid

Produced locally on demand

Examples= prostglandins, prostacyclin, thromboxanes

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2
Q

In general terms, how do NSAIDs work?

A

NSAIDs- inhibit down stream products of arachidonic acid by inhibiting COX (compete with arachidonic acid for hydrophobic site of COX)

Work as:

  1. Antipyretics
  2. Analgesics
  3. Anti-inflammatory
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3
Q

How is arachidonic acid synthesised from linoleic acid?

A

Linoleic acid obtained from diet- vegetable oils

Linoleic acid= converted hepatically to arachidonic acid (found throughout body- in particualr in muscle, brain and liver)

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4
Q

Differentiate between the 2 functional isoforms of cyclooxygenase enzymes.

A

(don’t need to learn table- not an exhaustive list)

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5
Q

Through what types of receptor do prostanoids act?

A

GPCRs

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6
Q

Give examples of 5 prostanoids.

A
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7
Q

Give 2 examples of substances which can enhance the action of prostanoids.

A

Local autocoids eg:

  1. Bradykinin
  2. Histamine
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8
Q

What effects do thromboxane (TXA2) and prostacyclin (PGI2) have on vasculature?

A

Thromboxane= vasoconstrictor

Prostacyclin= vasodilator

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9
Q

NSAIDs have 3 major actions: analgesic, anti-inflammatory and anti-pyretic. How do they work as analgesics?

A
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10
Q

NSAIDs have 3 major actions: analgesic, anti-inflammatory and anti-pyretic. How do they work as anti-inflammatories?

A

Symptomatic relief by COX inhibition- little/no effect on underlying condition

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11
Q

NSAIDs have 3 major actions: analgesic, anti-inflammatory and anti-pyretic. How do they work as anti-pyretics?

A
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12
Q

Name 6 NSAIDs and put them in order of increasing COX-2 or increasing COX-1 selectivity.

A
  1. Aspirin
  2. Ibruprofen
  3. Naproxen
  4. Diclofenac
  5. Celecoxib
  6. Etoricoxib
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13
Q

Differentiate between naproxen and naloxone

A

Naproxen= NSAID

Naloxone= opioid receptor antagonist (used for overdose)

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14
Q

What is the most common ADR for NSAIDs? Explain why.

A

GI upset

  • Dyspepsia
  • Nausea
  • Peptic ulceration
  • Bleeding
  • Perforation

Why?

COX enzymes inhibited, prostaglandin synthesis affected

Less mucus and bicarbonate secretion

More acid secretion

Less mucosal blood flow

Enhanced cytotoxcity and hypoxia

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15
Q

What are the cautions for prescribing NSAIDs?

A

GI

  • Can cause exacerbation of IBD
  • Loacl irritation and bleeding from rectal admin
  • Caution:
    • Elderly
    • Prolonged use
    • PPIs
    • Anticoagulants
    • Smoking
    • Alcohol
    • History of peptic ulceration
    • Helicobacter pylori
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16
Q

What effects do NSAIDs have on the kidneys? Explain why.

Who do we therefore need to be careful about prescribing NSAIDs to?

A
  • Decrease GFR (reversible)
  • Decrease renal blood flow (reversible)

Prostaglandins required for vasodilation and renal perfusion

Prostaglandins inhibit sodium absorption in collecting duct–> natriuresis

Cautions:

  • Underlying CKD
    Heart failure
  • Very young and elderly
17
Q

Give 2 examples of selective COX-2 inhibitors.

Explain why they generally have less GI ADRs.

A
  1. Celecoxib
  2. Etoricoxib

COX-2 inhibitors avoid inhibition of homeostatic actions mediated by COX-1

eg Platelets only have COX-1

18
Q

NSAIDs are susceptible to competitive displacement. Explain what this means and give examples of some drugs which compete with NSAIDs for protein binding.

A

NSAIDs= highly protein bound

NSAIDs–> displace other protein bound drugs–> increase free drug concentration

Examples:

  1. Sulfonylureas- hypoglycaemia
  2. Methotrexate- hepatotoxicity
  3. Warfarin- increased bleeding risk
19
Q

NSAIDs have lots of indications. List a few of them.

A
20
Q

Give some of the contraindications for NSAID use.

A

CVD risk increase associated with NSAID use

Impaired renal function

GI disease due to NSAID use

21
Q

Paracetamol is well absorbed from the GI tract. Where is it inactivated?

A

Inactivated primarily by conjugation in liver

22
Q

NAPQI (N-acetyl-p-benzoquinoneimine) is a highly reactive metabolite of paracetamol.

Conjugation with what molecule in the liver renders it harmless? How much paracetamol is required to cause irreversible damage?

A

NAPQI- conjugates with glutathione

150mg/kg= sufficient to cause ireversible damage

23
Q

If a patient has a paracetamol overdose;

  • How will they present?
  • How do find out the extent of the overdose?
  • How do we treat it? (why do we not just give glutathione?)
A
  • How will they present?
    • Can be asymptomatic for hours
    • Nausea, vomiting, abdominal pain (first 24hrs)
  • How do find out the extent of the overdose?
    • Blood after 4hrs- will know extent of overdose
  • How do we treat it? (why do we not just give glutathione?)
    • Give N-Acetylcysteine
      • Drives phase 2 metabolism
    • Glutathione- doesn’t get absorbed into hepatocytes