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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
What are the big toxicities from NSAIDS
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
26
What are some indications for ketoprofen
Labeled use for pain and inflammation associated with musculoskeletal disorders in horses
27
What is the PD for ketoprofen
Nonspecific COX inhibitor May also block leukotrienes synthesis
28
What are some adverse effects of ketoprofen
Inhibition of platelet aggregation
29
What are some indications for phenylbutazone
Labeled use for pain and inflammation in horses (common) and dogs (rare)
30
What is the PD for phenylbutazone
Cox-2 preferential inhibitor
31
What are important PK for phenylbutazone
High protein plasma binding and induces microsomal enzymes which can lead to tolerance with chronic administration
32
What are some adverse effects of phenylbutazone
Colic, vomiting, diarrhea, septicemia, oral and GI ulcers/erosion, renal papillary necrosis—> hypoproteinemia—> decrease blood volume—>hypovolemic shock—>circulatory collapse/ death
33
What are some contraindications for phenylbutazone
Suspected GI ulcers, bone marrow abnormalities, preexisting CHF or renal insufficiency, intracarotid administration- seizures
34
Phenylbutazone causes ___ in humans so handle with care
Aplastic anemia
35
What are some indications for flunixin meglumine
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
What is the PD for flunixin meglumine
COX2 preferential inhibitor in horses COX1 inhibitor in dogs (more adverse effects- GI and bleeding)
37
What are some adverse effects/ contraindications of flunixin meglumine
Arterial injection- ataxia, hypersalivation, muscle weakness IM injection causes local muscle damage Hypersensitivity reactions Suspected GI ulcers
38
What is carprofen labeled for
Musculoskeletal pain and inflammation in dogs
39
What is the PD for carprofen
COX2 preferential inhibitor
40
Carprofen has a high affinity for tissue proteins which may cause what
Sequestration at sites of inflammation resulting in prolonged effects
41
What species is at greater risk of toxicity with carprofen
Cats-glucuronidation
42
What are some adverse effects/ contraindications with carprofen
Hepatopathy, preexisting renal or hepatic abnormalities, gastritis, hypotension
43
What is meloxicam indicated for
Osteoarthritis, analgesia, and inflammation in dogs Labeled for pain in cats (SINGLE DOSE)
44
What is the PD for meloxicam
Cox-2 preferential inhibitor
45
What is one of the more safe NSAID options for dogs
Meloxicam
46
What are some adverse affects/ contraindications for meloxicam
GI effects Cats and dogs undergoing sx- bleeding risk Repeated use of meloxicam in cats associates with AKI and death
47
What species is deracoxib only used in
Dogs
48
What is deracoxib labeled for
Pain and inflammation associated with osteoarthritis and post sx pain
49
What is the PD for deracoxib
Cox-2 exclusive inhibitor
50
What are some adverse effects of deracoxib
Despite being cox-2 exclusive its not guaranteed so can act on cox-1 and cause inhibition of platelet aggregation
51
What are the indications for robenacoxib
Post sx pain, ELDU for acute musculoskeletal pain/inflammation in cats
52
What is the maximum days you can administer robenacoxib
3 days
53
What is firocoxib labeled for
Pain/inflammation associated with OA in dogs (3days) and horses (9-14 days), post sx pain in dogs ELDU for TCC in dogs
54
What is the PD for firocoxib
COX-2 exclusive inhibitor
55
What are some guidelines for safe use of NSAIDS
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
What is grapriprant indicated
Pain and inflamamtion associated with osteoarthritis in dogs only
57
What is the PD for grapiprant
EP4 receptor antagonist which is one of four PGE2 receptors so mediates inflammation in OA
58
Gapriprant is EP4 receptor antagonist, EP4 is the sole receptor that induces ___
Stomach acid secretion (Might be good option if gastric ulcers concern)
59
T or F: fast before giving grapiprant
False
60
What are some adverse effects of grapiprant
Vomiting, diarrhea, anorexia, inappetence, IMHA, buccal ulcers
61
Grapiprant is a __derivative so could be contraindicated in what breed
Sulfonamide, Doberman pinchers
62
What is frunevetmab and bendinvetmab indicated for
Pain/inflammation associated with OA in dogs (bendivetmab) and cats (frunevetmab)
63
What is the PD for frunevetmab and bedinvetmab
Antibodies binding nerve growth factor which blocks pain transmission to nerves Also inhibitors TrKA receptors on nerves and mast cells
64
What are some adverse effects of frunevetmab and bendinvetmab
Hypersensitivity Cats: skin abrasions, alopecia, scabs, ulceration, increased creatinine
65
What are some indications for amantidine
ELDU as adjunct tx for chronic and neuropathic pain in dogs and cats
66
Amantidine is generally administered with ___
NSAIDS, opioids or gabapentin
67
What is the PD for amantidine
NMDA receptor antagonist- which is important in ascending pain pathway to spinal cord Inhibits allodynia which is pain resulting from non-noxious stimuli
68
Chronic pain is sustained when __ and ___ bind ___ receptors
Glu, Asp, and NMDA receptors
69
What are some adverse effects/ contraindications for amantidine
GI effects CI in animals with renal or hepatic deficiency, CHF, dermatitis, CNS/seizure disorder

Pharmacology II (36 decks)

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