Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Principles of Science BVetMed 3 > NSAIDs 1 - Understanding the clinical pharmacology of NSAIDs and its relevance to clinical practice > Flashcards

NSAIDs 1 - Understanding the clinical pharmacology of NSAIDs and its relevance to clinical practice Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

How do NSAIDs reduce inflammation?

A

inhibit production of prostaglandins released by damaged tissue through inhibition of COX enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Clinical indications - NSAIDs

A
  • control pain in non-infectious/ non-allergenic inflammatory disorders (DJD, peri and post-op)
  • Decrease platelet aggregation (thromboembolus, heartworm disease)
  • Ophthalmology (rx of keratitis, scleritis, don’t inhibit corneal re-epithelialisation, intra-ocular sx as may minimise post-op increase protein content of AH).
  • Some immunological diseases (SLE and RA, anti-inflammatory, may stimulate T suppressor cells in their action against T helper cells and auto-Ab producing BCs)
  • endotoxic shock (LA only) but must be administered prior or immediately after onset of endotoxaemia with other supporive tx.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

COX1 - actions

A
  • produces prostaglandins important in physiological modulation of normal function:
  • gut mucosal barrier
  • intra-renal perfusion when renal BF decreased
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is COX-2 activated and released by?

A
  • tissue damage
  • bacterial lipopolysaccharide
  • cytokines
  • growth factors
  • inflammation where PGE2 predominates
  • important physiological functions (expressed constitutively in kidney macular densa to maintain renal perfusion by dilating afferent arteriole when vasoconstriction stimulated)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the COX1: COX2 ratio?

A
  • ratio of effect varies with different drugs (why some are more ulcerogenic than others and other toxicity profiles)
  • recent evidence shows the relative COX2 preference of a drug is influenced by the assay chosen, tissue type and species
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the gold standard assay for COX profile of a drug?

A

whole blood assay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Outline carprofen specificity

A
  • Dog = COX2 preferential (or non-selective)
  • Horse = non-selective
  • Cat = COX2 preferential (but significantly longer half-life than dog, daily dosing –> GIT disorder)
  • Man = COX1 preferential
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is a non-specific COX inhibitor?

A

one with no meaningful or clinical differences in COX1 or 2 inhibition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

COX2 inhibition - clinical benefits

A

Suppression of:

  • inflammation
  • pain
  • fever (some)
  • Alzheimer’s disease (this is an inflammatory process associated with COX2 increased expression, epidemiological studies suggest delayed expression and/or slow progression with NSAID use).
  • Some cancers (colon, pancrease, lung, TCC, melanoma)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

3 types of NSAID

A
  • non-selective
  • preferential (at least 2x greater inhibition of COX2 than -1 but usually 10-40)
  • selective (>100 times selective for COX2)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mechanisms of COX action

A
  • inhibition of COX isoforms
  • other actions at molecular levels peripherally and centrally (varies with drug)
  • Many contribute to pharmacological, toxocological and therapeutic properties (5LO inhibition, prostaglandin-R blockade, scavenging free radicals, anti-bradykinin properties, inhibition of enzyme release or action, inhibition of cytokine release, inhibition of NFkB)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pharmacodynamics - COX

A

usually expressed as IC50 values

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Assay methods - COX assay

A
  • cell based
  • tumour cell lines
  • whole blood (gold standard)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is COX1 inhibitory activity detected?

A

inhibition of clot-induced thromboxane B2 production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is COX2 inhibitory activity detected?

A

inhibition of LPS induced PGE2 production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What may influence safety of NSAIDs?

A
  • degree of acidity of the pro-drug (direct gastric mucosal damage)
  • plasma half life
  • degree of enterohepatic recycling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Therapeutic aim - NSAIDs

A
  • > 80% inhibition of COX2 (for p art though not all of 24hr)

- COX1 inhibition should be

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Examples - non-selective COX inhibitors

A
  • aspirin
  • phenylbutazone
  • ketoprofen
  • tolfenamic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Outline preferential COX-2 inhibitors

A
  • 2 to 40 x more selective for COX2
  • analgesic and anti-inflam. at doses that inhibit COX2 but not COX1
  • some COX1 inhibition at elevated or therapeutic dosages
  • includes drugs classes as coxibs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Examples - preferential inhibitors of COX2 (dog, cat)

A
  • meloxicam
  • Carprofen
  • Mavacoxib
  • Cimicoxib (probably)
  • Deracoxib (USA and Australia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Examples - UK selective inhibitors of COX2

A
  • firocoxib

- robenocoxib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Example - dual inhibitor (COX and LOX)

A

= TEPOXALIN (inhibit LOX for a short period during day, non-selective inhibitor of COX1 and COX2

23
Q

Which human NSAIDs are toxic to pets?

A
  • naproxen
  • ibuprofen
  • piroxicam (only use for TCC in veterinary)
  • mefanamic acid
  • diclofenac
  • paracetamol/acetaminophen (toxic to cats only)
24
Q

Effects of feline paracetamol ingestion

A
  • facial and paw oedema

- methaemoglobinaemia

25
Q

Pharmacokinetics - NSAIDs

A
  • well absorbed from stomach and SI
  • well absorbed after SC or IM injection
  • topical administration can result in measurable drug levels in tissues and synovial fluids comparable to that observed after oral administration
  • oromucosal delivery can achieve effective systemic levels (revitcam)
  • weak acids so readily penetrate inflamed tissue
  • highly protein bound (accumulation of drug in protein-rich inflammatory exudate)
  • duration of effect of NSAIDs may exceed apparent systemic half life
26
Q

Outline NSAID metabolism

A
  • excreted at various rates depending on metabolic pathway and extend of enterohepatic circulation
  • elimination half life varies considerably b/w drug and species
  • toxicity and pharmacokinetic data on one species can NEVER be transposed to another species
27
Q

Describe aspirin in dogs and cats

A
  • used in both

- prolonged half life in cats (thus same dose but q72hours not BID)

28
Q

Outline carprofen in dogs and cats

A
  • used in both
  • T(1/2) is 20 hours (Cat) vs 8 hours (dog)
  • only licensed for once only use in cats
29
Q

Outline meloxicam in dogs and cats

A
  • used in both

- 21 vs 24 hrs half life (similar but different doses)

30
Q

3 main NSAID side effect (systems)

A
  • GIT
  • renal
  • haematological
31
Q

What is prostaglandin role in GIT?

A

PGI2 and PGE2 maintain integrity of protective barrier that prevents gastric mucosa from damage by gastric acid by:

  • inhibit gastric acid secretion
  • maintain mucosal BF
  • involved in secretion and composition of healthy mucous
  • act as intercellular messengers to stimulate mucous cell tunrover and migration
  • COX1 is source of ‘good’ PGs
32
Q

Main mechanism that GIT ulceration occurs d/t NSAIDs

A

COX1 inhibition however both COX1 and 2 need to be inhibtied to generate mucosal injury in the absence of pre-existing injury

33
Q

Which gut cells express COX2? 4

A
  • macrophages
  • neutrophils
  • myofibroblasts
  • endothelial cells
34
Q

Can COX2 inhibition retard ulcer healing?

A

some studies suggest yes

- safety of COX2 inhibition in presence of inflammation needs to be demonstrated

35
Q

When is it good to avoid NSAIDs?

A

patients with confirmed, presumed or potential GIT inflammation including pancreatitis

36
Q

How else can NSAIDs cause GIT damage?

A
  • relative rate of gastric absorption
  • systemic availability of drug via circulation to mucosa
  • direct damage to gastric mucosa
  • degree of enterohepatic recycling
37
Q

What increases ulcerogenic potential of NSAIDs?

A
  • concurrent corticosteroids
  • dehydration
  • hypovolaemic shock
  • disruption of normal GIT BF
38
Q

Are COX presence in renal tissue?

A

IHC staining of normal renal tissue shows both COX1 and 2 thus COX2 has physiological role in normal kidney:

  • when renal perfusion is reduced, renal PGs maintain renal BF via vasodilatory actions (COX1 and 2)
  • natriuresis (COX2)
39
Q

Outline COX2 species differences

A
  • expression markedly increased in volume-depleted rats and dogs, not monkeys (thus preferential or selective COX2 inhibitors may not be as renally safe as thought in dogs vs primates).
40
Q

T/F: in a healthy, well-hydrate animal, reduced renal PG production is of little consequence

A

True

41
Q

When can significant renal toxicity result d/t NSAIDs?

A

If the animal is:

  • volume depleted
  • avidly retaining Na (CHF or hepatic cirrhosis)
  • has pre-existing renal insufficiency
42
Q

T/F: recent study showed cats with CKD on meloxicam for DJD had longer survival than those not on meloxicam

A

Ture

43
Q

Which NSAIDs are safest for kidney?

A

Preferential (carprofen, meloxicam) and to a greater extent selective (firoxib, robenacoxib, mavocoxib, cimicoxib) COX2 inhibitors have less risk of renal toxicity when renal perfusion is reduced than non-selective NSAIDs (aspirin, PBZ, ketoprofen, tepoxalin).

44
Q

T/F: no NSAID is completely renally safe when renal perfusion is reduced or may be reduced

A

True

45
Q

Normal effects - thromboxane - 2

A
  • potent vasoconstrictor

- activates platelet activation

46
Q

Effects of thromboxane inhibition

A

Can lead to increased risk of bleeding thus use any NSAID with care in breeds with high prevalence of vonWillibrands disease. (although usually only significant with older NSAIDs)

47
Q

Metabolism of NSAIDs - location

A

Extensive hepatic metabolism so care with hepatic disease

48
Q

Advice for NSAIDs with liver dz

A
  • critically review if NSAIDs really necessary
  • avoid
  • if essential, increase dose interval rather than decreasing dose
49
Q

When to be careful when using ACEI+NSAID?

A

if renal perfusion reduced –> advise owner to stop NSAID immediately if on this combination and becomes unwell

50
Q

What premeds shoudl you be careful with when using NSAIDs?

A
  • alpha 2 agonists

- avoid high dose ACP as predmed

51
Q

Effects of an NSAID + diuretic combination

A

COX2 inhibition may attenuate effect of diuretic

52
Q

Contraindications - NSAIDs (selective as well as non-selective)

A
  • evidence/ suspicion GIT inflammation
  • GIT BF reduce or may be reduced (shock, dehydration, reduced CO)
  • renal BF reduced or may be reduced
  • pathological Na retention present (nephrotic syndrome, cardiac failure, cirrhotic hepatic disease)
  • renal dysfunction (except old cats with DJD)
  • hepatic disease * if necessary use with increased dose interval to compensate for decreased rate of metabolism*
53
Q

What is essential for all patients on NSAIDs?

A
  • well-hydrated
  • good peripheral circulation
  • good renal function
  • normal sodium/water balance
  • ideally not have liver dz (if essential increase dosing interval)
  • not have or have potential GIT pathology
54
Q

What is an alternative to NSAIDs for analgesia?

A

opioid analgesics

Principles of Science BVetMed 3 (110 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions