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Case 1 > Non-steroidal anti-inflammatory drugs (NSAIDs) & paracetamol > Flashcards

Non-steroidal anti-inflammatory drugs (NSAIDs) & paracetamol Flashcards

1
Q

What is the function of phospholipase A2 (PLA2)?

A

to cleave fatty acids from the membrane phospholipids

PLA2 generates the most widely used fatty acid precursor: arachidonic acid

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2
Q

What kind of fatty acid is arachidonic acid?

A

a polyunsaturated omega-6 fatty acid

20:4(w-6)

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3
Q

What do lipoxygenases (LOX) do?

A

convert arachidonic acid into eicosanoids which are further modified to leukotrienes

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4
Q

What does prostaglandin-H synthase (PGHS) do?

A

convert arachidonic acid into endoperoxides (PGG2 and PGH2) which can then be modified into cell-specific prostanoids

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5
Q

Name some endoperoxides

A

PGG2 and PGH2

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6
Q

What is the ‘class action’ of NSAIDs?

A

inhibit COX-1 domain activity in prostaglandin-H synthase preventing generation of the precursor endoperoxides PGG2 and PGH2

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7
Q

What effect does PGE2 have on A-delta and C nociceptive neurons?

A

sensitises them to serotonin, bradykinin and ‘Substance P’

NSAID’s can inhibit this process

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8
Q

What enzyme is PGE2 derived from?

A

PGHS-2

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9
Q

What kind of pain relief would be given to someone suffering from moderate pain?

A

paracetamol and a weak opiod (codeine phosphate)

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10
Q

What kind of pain relief would be given to someone in mild pain?

A

paracetamol and/or NSAID

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11
Q

When are NSAIDs contra-indicated?

A

if pregnant

if already on a NSAID

do not use aspirin if younger than 16

if sensitised to salicylates/NSAID allergic

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12
Q

What syndrome is associated with giving aspirin to under 16’s?

A

Reye’s Syndrome

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13
Q

What are glycero-phospholipids?

A

fatty acids found in the cell membrane ‘fatty acid reservoir’

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14
Q

What are the two domains of the PGHS enzyme?

A

cyclo-oxygenase domain (COX)

peroxidase domain

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15
Q

What type of receptor do prostaglandins bind to on target cell membranes?

A

G protein-coupled receptors

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16
Q

Why are NSAIDs not as potent at reducing inflammation as steroids?

A

steroids inhibit enzyme phospholipase A2 which prevents formation of arachidonic acid (AA)

greater effect than NSAIDs because AA is a precursor for inflammatory mediators so has a wider ranging response

NSAIDs just block COX domain preventing formation of certain prostaglandins

17
Q

What is the mechanism of action of ibuprofen?

A

competes with AA for the COX domain active site of PGHS 1&2

it is a reversible competitive inhibitor

18
Q

What are the two adverse drug reactions associated with NSAID use that we should know about?

A

potential for gastric ulceration

compromised renal function

19
Q

Why do NSAIDs have a potential for gastric ulceration?

A

gastric mucosa protects itself from gastric acid with a layer of mucus

the secretion of this mucus is stimulated by prostaglandins

blocking the COX domain inhibits formation of prostaglandins and gastric mucus thins leaving the stomach vulnerable to peptic ulcers

20
Q

How do NSAIDs cause comprimised renal function?

A
21
Q

What are the signs and symptoms of Reye’s Stage 1?

A

rash on palms and feet

heavy vomiting

lethargy

confusion

nightmares

pyrexial and headaches

22
Q

What is the mechanism of action of aspirin?

A

irrerversible inhibition of the cyclo-oxygenase domain of prostaglandin-H synthase

other NSAIDs are reversible inhibitors

23
Q

What are the signs and symptoms of Reye’s Stage IV?

A

deepening coma

hepatic dysfunction

mydriasis (dilation of pupil) with minimal response to light

24
Q

What are the signs and symptoms of Reye’s Stage III?

A

more stage I and II symptoms

potential for coma, cerebral oedema, occasionally respiratory arrest

25
Q

What are the signs and symptoms of Reye’s Stage II?

A

encephalitis-induced stupor

hyperventilation

fatty liver (steatosis)

hyperactive reflexes

26
Q

What does the perioxidase domain of prostaglandin-H-synthase do?

A

converts prostaglandin G to prostaglandin H2

27
Q

What is the precursor endoperoxide that all prostanoids originate from?

A

PGH2

Case 1 (10 decks)

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