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1. Pharmacology > NSAIDS > Flashcards

NSAIDS Flashcards

1
Q

Non-steroidal anti-inflammatory drugs that include:

A

Over the counter (OTC)
Prescription
Non-opiods

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2
Q

Clinical uses of NSAIDS

A

Musculoskeletal pain (OA, muscle, tendon/lig, fracture)
Visceral pain (abdominal and thoracic)

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3
Q

Pain pathway intervention

A

Anti-inflamm. agents, COX 2 inhibitor

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4
Q

COX 1(constitutive)

A

Housekeeping function: physiological stimuli
PGI2: renal function
TXA2: platelet function
PGE2: gastric protection

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5
Q

PGI2 (prostacyclin)

A

Localized in vasculature tissue
Potent vasodilator
Exerts antiaggregaotry activity on blood platelets

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6
Q

TXA2 (thomboxane)

A

Vasoconstrictor and proaggregate in thrombus formation
Dominates in platelets

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7
Q

PGE2

A

Direct vasodilator
Relaxes smooth muscle
Inhibits NE release
Suppresses T cell receptors signaling
Fever

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8
Q

COX2 (inducible)

A

Pathological condition: inflammatory stimuli
Inflammatory sites (macros) → Pro-inflammatory PGs and other inflammatory mediators → Inflammation

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9
Q

NSAIDs are more selective for __________

A

COX2

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10
Q

Screening test: COX ratio

A

IC50 (COX1) :IC50 (COX 2)
Compare potency of drug towards COX isofroms

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11
Q

<1 or close to 1 COX ratio

A

Less concentration to inhibit COX1
More concentration to inhibit COX2
Classic NSAID

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12
Q

> 1 COX ratio

A

Less concentration to inhibit COX2
More potent for COX2
Preferential or selective NSAID

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13
Q

Side effects of prolonged COX 2 inhibition

A

Disturb balance between p PGI2 andp TxA2
LEADING TO ↑ PLATELET AGGREGATION AND VASOCONSTRICTION

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14
Q

Classical NSAIDs

A

Aspirin
Flunixin meglumine
Phenylbutazone
Acetaminophen* (paracentamol)

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15
Q

What do classical NSAIDS do?

A

Inhibits COX 1 and COX2 equally leading to ↓ inflammatory response

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16
Q

Preferential NSAIDs

A

Inhibits COX2 more than COX1
Carprofen and meloxicam

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17
Q

COX2 selective (Coxib) NSAIDs

A

Inhibits COX2 wayyy more than COX1
Firocoxib, robenacoxib, deracoxib

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18
Q

EP4 Antagonist drugs

A

Grapiprant (galiprant)

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19
Q

NSAID adverse effects on the GI tract

A

Gastroduodenal ulcer, GI bleeding
Dogs > cats, horses (colitis)
Most common cause: OVERDOSING
Risk factors: geriatric patients, concurrent use of gluccos

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20
Q

Pathogenesis of COX inhibitors

A

Direct irritation (acid)
Inhibition of gastro protection

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21
Q

Prevention and treatment

A

Accurate dosing
Anti-ulcer drugs: H2 antagonists (famotidine), proton pump inhibitors (omeprazole), PGE analogue (misoprostol)

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22
Q

How do PGs affect the kidney?

A

Insure intramedullary renal blood flow
Urine formation

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23
Q

NSAID Renal adverse effects

A

Analgesic nephropathy
Doesn’t occur in healthy animals with free water
↓ GFR, water retention, hypertension

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24
Q

Patients at risk for renal adverse effects

A

↓ blood flow to kidneys
Geriatric patients
Concurrent use of nephrotoxic/ active drugs

25
Q

Effects of Classical NSAIDS on normal blood vessels

A

Inhibits COX 1, COX2 andPGI2 →vasodilation and inhibiting platelet aggregation

26
Q

Effects of classical NSAIDS on damaged BVs

A

Inhibits COX 1 and TxA2 → vasoconstriction and promotes platelet aggregation

27
Q

Effects of aspirin on BVs (damage and normal)

A

Prolonged bleeding time (withhold aspirin before surgeries)

28
Q

Effects of Coxib on BVs (damage and normal)

A

Enhance blood clot formation and induce cardiovascular disease (banned for humans)

29
Q

Hemopoietic NSAID adverse events

A

Stop platelet aggregation and prolonged bleeding time
Bone marrow depression
Thromboembolic disease (COX2 selective NSAIDs)

30
Q

What drug cannot be used in cats due to bone marrow depression?

A

Phenybutazone

31
Q

NSAID effects on Reproduction

A

Prolonged gestation (inhibition of uterine PGF2 and PGE2)
Lysis of corpus luteum
Initiates uterine contractions

32
Q

NSAID PK

A

Weak acids (stomach ulcers), oral absorption
Highly > 90% bound to albumin
Hepatic Metabolism
Enantiomers

33
Q

Acetaminophen (parcetamol)

A

Inhibition of peroxidase (POX)
Centrally acting analgesic and anti-pyretic
Poor anti-inflammatory

34
Q

Acetaminophen contraindications

A

CATS
Deficiency in glucuronyl trasnsferase → hepatic toxicity and methemoglobinemia

35
Q

Acetaminophen toxicity treatment

A

Promote glutathione formation (N-acetylcysteine and SAMe)
Microsomal enzyme inhibitor (cimetidine)
Anti-oxidants (vitamin C and SAMe)

36
Q

Aspirin

A

Salicylic acid
Hepatic conjugation with glucuronide and renal excretion

37
Q

Adverse effects of aspirin

A

Irreversible inhibition of platelet activity
CS: depression, vomiting, electrolyte imbalances, hyperthermia, convulsions, death, cartilage damage

38
Q

Flunixin meglumine

A

Nicotonic acid
Used for visceral pain (horse colic) and endotoxemia
Injectable, oral paste, granules

39
Q

Flunixin meglumine in food animals

A

Approved for use in cows for pyrexia
Prohibited (veal calves and lactating dairy cattle)

40
Q

Adverse effects of Flunixin meglumine

A

Mask surgical pain in equine patients
Gastric ulceration
Clostridial myositis from IM injection

41
Q

Phenylbutazone

A

Pyrazolone (enolic acid)
Used for musculoskeletal pain in horses and cattle
Used in dogs, toxic in cats

42
Q

Phenylbutazone disposition

A

Metabolized by liver, highly protein bound (may displace other drugs)
Excreted in urine (alkaline ↑ excretion)

43
Q

Phenylbutazone adverse agents

A

Narrow TI
Gastrointestinal ulcerations
Low serum protein concentrations
Extravasation of IV product
Renal papillary necrosis

44
Q

GI ulceration treatment

A

Proton pump inhibitors (omeprazole)
PGE replacement (misoprostol)

45
Q

Carprofen

A

Proprionic acid
First COX2 preferential drug approved in use in animals
Treats OA, preoperative management of pain

46
Q

Carprofen adverse effects

A

Safest of new NSAID
Hepatotoxicity
Renal tubular disease

47
Q

Meloxicam

A

Oxicam
OA in dogs
Post operative pain in cats
Popular in zoo, exotic wildlife

48
Q

Meloxicam in dogs and cats

A

Cats: single dose only, renal failure, death, black box warning
Dogs: GI perforation

49
Q

Firocoxib

A

Canine chew and equine injectable and paste
Used for OA
Loading dose required

50
Q

Deracoxib

A

First coxib approved for use in animals
For OA in dogs and operative pain

51
Q

Robenacoxib

A

OA for dogs and cats and post-operative pain
Tissue selective - longer at the site of inflamm

52
Q

Gapiprant (galliprant)

A

EP4 receptor antagonist located @ sensory nerve ending
Dogs to control pain and inflamm. (OA)

53
Q

Nerve growth factor

A

Produced by inflammatory cells
Binds to sensory nerve ending (↑ pain signal rate, releases more cytokines and proliferation)

54
Q

NGF Inhibitor

A

Reduces pain signals
Reduce production of inflammatory repsonse
Monoclonal Ab
Ex: Bedinbetmab (dogs), frunevetmab (cats)

55
Q

Bendinvetmab (Librela in dogs)

A

Monthly SC injection for OA pain in dogs
Contraindication: hypersensitivity, dogs under 12m, lactating, breeding or pregnant animals

56
Q

Frunevetmab (Solensia in cats)

A

Pain due to OA, monthly Sc injection
Contraindications: Under 12 m or under 2.5 kg, breeding, lactating or pregnant animals

57
Q

Side effects of frunevetmab

A

Scabbing on head and neck, dermatitis and pruritus

58
Q

Contraindications for NSAIDs

A

Acute renal and hepatic insufficiency
Dehydration
Hypotension
↓ circulating blood volume: CHF ascites, hemorrhage, shock
Bleeding disorders/ coagulapathies
GI ulceration

1. Pharmacology (29 decks)

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