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Pharmacology II > Lecture 6: Non-opioid Analgesics > Flashcards

Lecture 6: Non-opioid Analgesics Flashcards

1
Q

How does histamine affect vasodilation, vascular permeability, chemotaxis and pain

A

Does vasodilation and increases vascular permeability

No chemotaxis or pain

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2
Q

How does serotonin affect vasodilation, vascular permeability, chemotaxis, pain

A

Maybe does vasodilation, increases vascular permeability

No chemotaxis and pain

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3
Q

How does bradykinin affect vasodilation, vascular permeability, chemotaxis and pain

A

Causes vasodilation, increases vascular permeability and pain

Does not cause chemotaxis

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4
Q

How do prostaglandins affect vasodilation, vascular permeability, chemotaxis and pain

A

Does all them

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5
Q

How do leukotrienes affect vasodilation, vascular permeability, chemotaxis and pain

A

Increases vascular permeability, and chemotaxis
No vasodilation or pain

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6
Q

What two pathways produce arachidonate

A
  1. Phospholipids via PLA2
  2. Diacylglycerols via D2 lipase
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7
Q

What is causes arachidonate acid to form prostaglandins

A

Cox-1 and 2

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8
Q

What 3 products result from prostaglandin production

A
  1. Prostanoids
  2. Other prostaglandins
  3. Thromboxanes (platelet aggregation)
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9
Q

T or F: Cox 1 is conditionally expressed, inducible

A

False, COX-1 is always expressed

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10
Q

What is COX-1 important for

A

Maintenance of normal physiology like mucous secretion and control over vasoconstriction of renal artery—> results in vasodilation in order to keep BF to kidneys up

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11
Q

T or F: COX-2 is conditionally expressed

A

True

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12
Q

COX-2 is produced in response to what

A

Cytokines, tumor promoters, and growth factors

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13
Q

COX-2 generates a ___inflammatory feedback loop

A

Positive

Inflammation—> increase PG—> increase leukotrienes—> increase cytokines—> increase COX-2 and repeat

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14
Q

What are the physiological effects of acetaminophen for COX inhibition

A

Analgesia and anti-pyretic

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15
Q

What are the physiological effects of aspirin for COX inhibition

A

Analgesia, anti-pyretic, anti-inflammatory, anti-thrombotic

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16
Q

What are the physiological effects of NSAIDS for COX inhibition

A

Anti-pyretic, anti-inflammatory, analgesia

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17
Q

What drug is occasionally added in for pain control in dogs and is highly toxic in cats

A

Acetaminophen

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18
Q

What is the investigational drug in saddle thrombi

A

Aspirin

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19
Q

What drugs may have minor and variable anti-thrombotic effects

A

NSAIDS

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20
Q

increased COX-2 specificity should reduce inflammation and also have less effects on the production of normal ____

A

Prostanoids needed for physiological function (mucus secretion and vasodilation of renal artery)

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21
Q

What conditions are the most common chronic labeled indications for use of NSAIDS

A

Musculoskeletal pain, inflammation and osteoarthritis

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22
Q

In OA NSAIDS target inflammation primarily occurring in the ___ and also ___

A

Synovium, articular cartilage

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23
Q

How do NSAIDS work in OA

A

Reduce the production of PGE2 by synovicytes and chondrocytes

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24
Q

PGE2 directly contributes to inducing ___ and promotes secretion of ___ that contribute to ____ leading to ___

A

apoptosis of chondrocytes
Promotes secretion of IL-1, NO, and TNFalpha that contribute to cartilage breakdown leading to synovitis and chondrocytes apoptosis

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25
Q

What are the big toxicities from NSAIDS

A
  1. Gastric ulcers (bleeding, vomiting, diarrhea)
  2. Hepatotoxic
  3. Nephrotoxic- acute renal failure, interstitial nephritis, glomerulonephropathy
  4. Bleeding- worse with nonspecific COX-2, sx concern and bleeding disorders
  5. Hypersensitivity reactions
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26
Q

What are some indications for ketoprofen

A

Labeled use for pain and inflammation associated with musculoskeletal disorders in horses

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27
Q

What is the PD for ketoprofen

A

Nonspecific COX inhibitor

May also block leukotrienes synthesis

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28
Q

What are some adverse effects of ketoprofen

A

Inhibition of platelet aggregation

29
Q

What are some indications for phenylbutazone

A

Labeled use for pain and inflammation in horses (common) and dogs (rare)

30
Q

What is the PD for phenylbutazone

A

Cox-2 preferential inhibitor

31
Q

What are important PK for phenylbutazone

A

High protein plasma binding and induces microsomal enzymes which can lead to tolerance with chronic administration

32
Q

What are some adverse effects of phenylbutazone

A

Colic, vomiting, diarrhea, septicemia, oral and GI ulcers/erosion, renal papillary necrosis—> hypoproteinemia—> decrease blood volume—>hypovolemic shock—>circulatory collapse/ death

33
Q

What are some contraindications for phenylbutazone

A

Suspected GI ulcers, bone marrow abnormalities, preexisting CHF or renal insufficiency, intracarotid administration- seizures

34
Q

Phenylbutazone causes ___ in humans so handle with care

A

Aplastic anemia

35
Q

What are some indications for flunixin meglumine

A

LU for musculoskeletal pain and visceral pain from colic in horses

LU for pyrexia associated with BRD, acute mastitis and endotoxemia in cattle

LU for Pyrexia associated with SRD in swine

36
Q

What is the PD for flunixin meglumine

A

COX2 preferential inhibitor in horses
COX1 inhibitor in dogs (more adverse effects- GI and bleeding)

37
Q

What are some adverse effects/ contraindications of flunixin meglumine

A

Arterial injection- ataxia, hypersalivation, muscle weakness
IM injection causes local muscle damage
Hypersensitivity reactions
Suspected GI ulcers

38
Q

What is carprofen labeled for

A

Musculoskeletal pain and inflammation in dogs

39
Q

What is the PD for carprofen

A

COX2 preferential inhibitor

40
Q

Carprofen has a high affinity for tissue proteins which may cause what

A

Sequestration at sites of inflammation resulting in prolonged effects

41
Q

What species is at greater risk of toxicity with carprofen

A

Cats-glucuronidation

42
Q

What are some adverse effects/ contraindications with carprofen

A

Hepatopathy, preexisting renal or hepatic abnormalities, gastritis, hypotension

43
Q

What is meloxicam indicated for

A

Osteoarthritis, analgesia, and inflammation in dogs

Labeled for pain in cats (SINGLE DOSE)

44
Q

What is the PD for meloxicam

A

Cox-2 preferential inhibitor

45
Q

What is one of the more safe NSAID options for dogs

A

Meloxicam

46
Q

What are some adverse affects/ contraindications for meloxicam

A

GI effects
Cats and dogs undergoing sx- bleeding risk

Repeated use of meloxicam in cats associates with AKI and death

47
Q

What species is deracoxib only used in

A

Dogs

48
Q

What is deracoxib labeled for

A

Pain and inflammation associated with osteoarthritis and post sx pain

49
Q

What is the PD for deracoxib

A

Cox-2 exclusive inhibitor

50
Q

What are some adverse effects of deracoxib

A

Despite being cox-2 exclusive its not guaranteed so can act on cox-1 and cause inhibition of platelet aggregation

51
Q

What are the indications for robenacoxib

A

Post sx pain, ELDU for acute musculoskeletal pain/inflammation in cats

52
Q

What is the maximum days you can administer robenacoxib

A

3 days

53
Q

What is firocoxib labeled for

A

Pain/inflammation associated with OA in dogs (3days) and horses (9-14 days), post sx pain in dogs

ELDU for TCC in dogs

54
Q

What is the PD for firocoxib

A

COX-2 exclusive inhibitor

55
Q

What are some guidelines for safe use of NSAIDS

A
  1. Labeled use
  2. Lowest effective dose
  3. Shortest possible duration
  4. Ensure no underlying renal or hepatic disease
  5. Monitor hydration
  6. Don’t give to hypovolemic
  7. Do not co-administer with other nephrotoxic, anti-coagulant or hepatotoxic drugs
  8. Avoid use with glucocorticoids and NSAIDS
  9. Co-administer with gastric protectants
56
Q

What is grapriprant indicated

A

Pain and inflamamtion associated with osteoarthritis in dogs only

57
Q

What is the PD for grapiprant

A

EP4 receptor antagonist which is one of four PGE2 receptors so mediates inflammation in OA

58
Q

Gapriprant is EP4 receptor antagonist, EP4 is the sole receptor that induces ___

A

Stomach acid secretion

(Might be good option if gastric ulcers concern)

59
Q

T or F: fast before giving grapiprant

A

False

60
Q

What are some adverse effects of grapiprant

A

Vomiting, diarrhea, anorexia, inappetence, IMHA, buccal ulcers

61
Q

Grapiprant is a __derivative so could be contraindicated in what breed

A

Sulfonamide, Doberman pinchers

62
Q

What is frunevetmab and bendinvetmab indicated for

A

Pain/inflammation associated with OA in dogs (bendivetmab) and cats (frunevetmab)

63
Q

What is the PD for frunevetmab and bedinvetmab

A

Antibodies binding nerve growth factor which blocks pain transmission to nerves

Also inhibitors TrKA receptors on nerves and mast cells

64
Q

What are some adverse effects of frunevetmab and bendinvetmab

A

Hypersensitivity
Cats: skin abrasions, alopecia, scabs, ulceration, increased creatinine

65
Q

What are some indications for amantidine

A

ELDU as adjunct tx for chronic and neuropathic pain in dogs and cats

66
Q

Amantidine is generally administered with ___

A

NSAIDS, opioids or gabapentin

67
Q

What is the PD for amantidine

A

NMDA receptor antagonist- which is important in ascending pain pathway to spinal cord

Inhibits allodynia which is pain resulting from non-noxious stimuli

68
Q

Chronic pain is sustained when __ and ___ bind ___ receptors

A

Glu, Asp, and NMDA receptors

69
Q

What are some adverse effects/ contraindications for amantidine

A

GI effects
CI in animals with renal or hepatic deficiency, CHF, dermatitis, CNS/seizure disorder

Pharmacology II (18 decks)

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