NSAID Flashcards

1
Q

What can Arachidonic acid be converted into and by what?

A

Lipoxins by 15-lipoxygenase
Prostanoids by Cyclooxygenase
Leukotrienes by 5-lipoxygenase

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2
Q

What are the different type of prostanoids?

A

Prostacyclin
Classical prostaglandins
Thromboxane

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3
Q

What is the effect of Prostacyclin?

A

Vasodilation
inhibit platelet aggregation

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4
Q

What is the effect of classical prostaglandins?

A

Increase vascular permeability and pain

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5
Q

What is the effect of thromboxanes?

A

Vasoconstriction and platelet aggregation

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6
Q

What are the effects of Aspirin?

A
  1. Analgesic
    2.Anti-pyretic (by blocking prostaglandin)
    3.Anti platelet
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7
Q

Explain the “analgesic ceiling” effect of Aspirin

A

Production of prostaglandin (which causes pain) is blocked by Aspirin. –> this sensitive the nociceptive fibres to stimulation by other inflammatory mediator, making them more sensitive to other compounds like Bradykinin and leukotrienes which can result in pain sensation

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8
Q

Explain why Aspirin is antiplatelet even though it inhibits production of prostacyclin (inhibits platelet aggregation)

A

Aspirin inhibits both Prostacyclin (which inhibits platelet aggregation) and Thromboxane A2 ( which promotes platelet aggregation)

PGI2 can be restored by synthesis of new COX enzyme which takes a few hours while TXA2 can only be restored by the formation of new platelets which takes 1-2 weeks

Net effect of inhibit platelet aggregation

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9
Q

Aspirin is a ____ (reversible/irreversible) COX inhibitor

A

Irreversible

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10
Q

What can aspirin be used for?

A

Aspirin is used at low dose as a blood thinner in cardiovascular diseases

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11
Q

What are the adverse effect of aspirin?

A

COX inhibition –> Salicylate toxicity when at high doses ( GI intolerance and tinnitus)

Always linked to Reye’s Syndrome. Children with viral infection could develop encephalitis (swelling of brain), hepatomegaly. Contraindicated in children

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12
Q

When is aspirin given in children?

A

Kawasaki Syndrome when there is high risk of cardiovascular complications including aneurysm and impaired blood flow to periphery.

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13
Q

What are some adverse effect of typical NSAIDS?

A

PGE2 (prostaglandin)
- Reduce gastric acid section
-increase mucosal blood flow
-increase secretion of mucus
- increase secretion of bicarbonate

Ulcer formation and haemorrhage risk in chronic users

Inhibition of PGE 2
- Sodium and water retention
- Peripheral edema
- Hypertension

Inhibition of PGI 2
- Suppression of renin/aldosterone secretion
- Hyperkalemia
- Acute renal failure

Other effects
- Bronchospasm in asthmatics due to excess leukotrienes due to “back damping effect
- Failure of haeomostasis, bruising
- Pseudo-allergic reaction: rashes, swelling, itching, nasal
congestion, anaphylactic shock

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14
Q

What are the typical NSAID and what are they used for?

A

Typical NSAIDS:

  1. Naproxen
    a. More effective in women (higher free fraction) used for dysmenorrhea
  2. Indomethacin
    a. Strongly anti-inflammatory due to additional steroid-like phosphlipase A inhibition
    b. But CNS adverse effects (confusion, depression, psychosis)
  3. Diclofenac
    a. Short plasma half-life, therefore low GI risk
    b. Long half-life in synovial fluid, used for inflammatory joint disease
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15
Q

What are the main function of COX-1 and COX-2?

A

Constitutive COX-1: responsible for house keeping, physiological function
- production of TbA2,PGI2,PGE2

Inducible COX-2: Inflammation
- production of PGI2 and PGE2

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16
Q

Why do we use COX-2 selective inhibitors?

A

Since COX-2 do not produce TXA2, Prescence of TXA2 allows for platelet aggregation –> lower risk of bleeding due to increase clotting –> lower risk of peptic ulcer

This is preferred over to non selective COX inhibitors which stop TXA2 production , increasing risk of bleeding and peptic ulcer

17
Q

What are some COX-2 selective inhibitor?

A

Celecoxib
Etoricoxib
Meloxicam
Diclofenac

18
Q

What is a major contraindication of COX-2 inhibitor (including non-selective) NSAID?

A

Contraindicated in third trimester of pregnancy

19
Q

What are some unwanted effects of COX-2 inhibition?

A
  • Renal toxicity (COX-2 in kidney)
  • Delayed follicular rupture during ovulation
  • Thrombosis due to increased COX-1 activity and TxA 2 production
  • Premature closure of ductus arteriosus in late pregnancy
  • Impairment of wound healing (exacerbation of ulcers)
20
Q

What is the mechanism of action of Paracetamol?

A

CNS-Selective COX inhibition

21
Q

Why is acetaminophen (paracetamol) used more commonly now?

A

Good antipyretic, spares GI tract, few AE and Se, few DDI

22
Q

Disadvantages of paracetamol

A

-weak anti inflammatory
-overdose cause liver damage
- allergic reaction