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Pharmocolgy > NSAIDs > Flashcards

NSAIDs Flashcards

1
Q

what are eicosanoids made from ?

A

Arachidonic acid

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2
Q

where does arachidonic acid come from?

what does it go into?

A 
linoleic acid (veg oils) and converted in liver
phospholipids
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3
Q

what enzyme releases Arachidonic acid ?

A

Phospholipase A2

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4
Q

What does PGE2 do ?

A

GI mucosa protection

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5
Q

what does PGI2 do?
what is it balanced by ?
what can imbalance lead to ?

A

inhibits platelets , vasodilator
TXA2
Hypertnesion, MI and stroke

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6
Q

what is the difference between COX-1 and 2 ?

A

constitutively active = 1

Inducable in active/inflamed tissue = 2

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7
Q

where is arachidonic acid most abundant ?

A

muscle , liver, brain and kidneys

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8
Q

What are the 3 prostanoids for pain , pyrexia and inflammation?

A

PGE2, PGF2, PGD

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9
Q

What are the pathological functions of COX-1?

A

chronic inflammation and pain

Raised BP

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10
Q

What are the pathological functions of COX-2?

A

chronic inflammation and pain
fever , blood vessel permeability
tumour cell growth

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11
Q

what other autacoids enhance action of prostanoids ?

A

Bradykinin and histamine

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12
Q

why does fish oil reduce CVD incidence ?

A

EPA and DHA (Omega 3 FAs) convert TXA3 and PGE3 so balance shifted to prostacyclin activity

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13
Q

what is the main difference between aspirin and other NSAIDs?

A

aspirin irreversibly inhibits COX

compared to competitive inhibitors of arachidonic acid

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14
Q

why do you see reduction in platelets still when aspirin is stopped ?

A

platelets are non nucleic so new platelets take time to synthesis from megakaryocytes

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15
Q

explain the analgesic action of NSAIDs

A

local action at site due to increased efficacy at inflammation
Central action = decrease in PGE2 synthesis in dorsal horn - less neurotransmitter released = less excitability of neurones in pain

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16
Q

explain anti-inflammatory effects of NSAIDs

A

reduction in production of PGs especially PGE2 and PGD2 released during injury

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17
Q

Explain Anti-pyretic effect of NSAIDs

A

inhibition of hypothalamic COX-2 where cytokine induced PGs synthesis elevated - only lowers temp if raised

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18
Q

list the most Cox-1 selective compound to least (first 4)

A 
Aspirin 
ibuprofen 
naproxen 
diclofenac 
celecoxib (pare and etori)
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19
Q

how can leukotrienes be affected by NSAIDs?

A

Inhibition of PGE2 leads to less leukoteienes

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20
Q

which type of NSAIDs are more selective at therapeutic doses ?

A

COX-2 inhibitors

21
Q

what are the PKs of NSAIDs?

A, D , M and E?

A

A= GI
D= Accumulate at site of action, Small Vd so protein bound
M = don’t undergo first pass metabolism
liver converts to inactive form

22
Q

how does aspirin OD work ?

A

converted to salicyclic acid then conjugation with glycine which saturates at high doses to go from 1st order to zero order

23
Q

what are GI ADRs of NSAIDs ?

A

dyspepsia , nausea , peptic ulceration , bleeding and perforation
exacerbation of IBDs
local irriation and bleeding fro rectum

24
Q

what can put you at risk for GI ADRs?

A

age, duration of use, glucocorticoid steroids, anticoagulants, smoking, alcohol, history of peptic ulceration and H Pylori

25
Q

how does NSAIDs causes GI ADRs?

A

decrease in :
mucus and bicarb secretion and increase in acid
mucosal blood flow –> hypoxia
hydrophobicity of mucus due to acidic nautre of NSAIDs

26
Q

what are the renal ADRs of NSAIDs?

A

decrease ADRs and renal medullary blood flow
increase in creatinine
hyperkalaemia
hypertension and oedema

27
Q

why does the renal ADRs of NSAIDs occur ?

A

AA vasodilators are not present leading to decreased renin (hyperkalaemia) and increased salt and water retention due to NaK2Cl upregulation

28
Q

Name 2 Cox-2 inhibitors

A

Celecoxib
Etoricoxib
Parecoxib

29
Q

why are Cox-2 not that selective?

A

Polymorphisms in Cox-2

patients often take non-selective before

30
Q

Can Cox-2 inhibitors stop platelet aggregation ?

A

No, but they impair PGI2 potentially leading to unopposed aggregatory effects

31
Q

what CVS ADRs are seen in mostly in COX-2 selectives?

A

salt water rentention = increase in BP
Vasoconstriction - reduced inhibition of ADH by prostaglandins
Efficacy of Antihypertensives reduced
risk of MI with traditional as well

32
Q

when should you not prescribe NSAIDs ?

A

pro-thrombotic risk
coronary or cerebrovascular diseases
excluding low dose aspirin

33
Q

why does combination NSAIDs cause increase risk of ADRs?

A

competitive displacement due to protein binding - PK and PD affected

34
Q

Name 4 high protein bound drugs and their increased risk of ADRs with NSAIDs

A

Sulfonylurea - hypoglycaemia
Methotrexate - Hepatotoxicity and leukopenia
Warfarin
Low dose aspiring - competition for COX-1 = Decrease CVS protection
also look out for diuretics

35
Q

why cant you give aspiring to children under 12 ?

A

increased risk of Reye’s syndrome - a rapid progressive encephalopathy

36
Q

what are the ADRs of NSAIDs in pregnant women ?

A

Delayed labour
increase blood loss
premature closure of ductus arteriosus
use paracetamol instead

37
Q

name 4 indication for use of NSAIDs

A 
Inflammatory conditions - joints and soft tissue
OA- try topical / paracetamol 
Post op pain
topical on cornea 
menorrhagia 
close ductus arteriosus
38
Q

Where is COX-2 expressed constitutively ?

A

renal arterioles and cells following inflammation

39
Q

what is the MOA for paracetamol?

what limits its actions ?

A

COX-2 inhibition in CNS = decreases pain signals to higher centres
Perioxidases in peripheral inflammation = little inflammatory effect

40
Q

what must you be careful of when prescribing paracetamol?

A

OTC medications that already have paracetamol = risk of OD

41
Q

what is a metabolite of paracetamol? how it is minimised ? how does it cause damage?

A

NAPQI via Phase 1 (CYP450)
Conjugation with glutathione
Highly nucleophilic = oxidising thiol groups on enzymes leads to cell necrosis / apoptosis
- 150mg/kg for OD

42
Q

Why don’t you give glutathione in paracetamol OD?

A

cannot enter the hepatocytes

43
Q

How would a paracetamol OD present ?

A

Nausea , vomiting, abdo pain - first 24 hours

liver damage / UQ pain - 24 to 48

44
Q

what is a good indicator of damage from paracetamol OD?

A

Prothrombin time

45
Q

why are Blood tests a sort of red herring in paracetamol OD?

A

They do not show extent of overdose if multiple doses

46
Q

what should you give in for paracetamol OD?

A

Activated charcoal if very early

acetylcystiene

47
Q

why is alcohol bad with paracetamol ?

A

induces phase 1 metabolism to make more NAPQI

48
Q

CVS ADRs are more prone to which type of NSAID?

A

it is not class specific so neither

Pharmocolgy (22 decks)

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