NSAIDS #2 Flashcards
1
Q
How are NSAIDs classified?
A
- Inhibitors of Prostanoids (PGs, TXA2)
- Miscellaneous Anti-Inflammatory Drugs
2
Q
NSAIDs: Mechanisms of Action
A
3
Q
NSAIDs: Adverse Effects
A
High doses
Long exposure
▪ Vomiting
▪ Diarrhea
**▪ GI ulceration, hemorrhage, and perforation
▪ Hepatotoxicity
▪ Renal toxicity
▪ Cardiovascular and blood toxicity
▪ CNS depression
▪ Circulatory disturbances
▪ Drug-drug interaction
4
Q
NSAIDs that are used most commonly in humans can cause poisoning in small animals are?
A
Aspirin
Acetaminophen
Ibuprofen
Indomethacin
Naproxen
Pneumonic: IIAN
5
Q
A
6
Q
List the Desirable Features of NSAIDs
▪ Deactivate/desensitize _________ (_____)
▪ Attenuate ___________ response
▪ Synergistic with _______
▪ No ___________ or __________
▪ No ____________ depression
▪ Minimal ?
▪ ____ duration of action
▪ No ________ side effects
A
nociceptors, pain, inflammatory, opioids, addiction, dependence, respiratory, nausea/vomiting, Long, cognitive
7
Q
COX-1 mediates ?
A
physiological responses (GI protection, platelet aggregation)
8
Q
COX-2 is expressed by cells involved in ____________ (e.g.?) is responsible for
the synthesis of _____ and _____
A
inflammation, macrophages, monocytes, PGs, TXA2
9
Q
Selective inhibition of COX-2 might have ?
A
better therapeutic responses
10
Q
Selectivity of COX2 versus COX1 is often expressed as the?
A
COX1/COX2 inhibitory ratio
11
Q
Write the inhibitory effect ratio.
If ratio is > _____, the drug is more specific for COX-2.
A
The inhibitory effect (IC50) = COX-1/COX-2;
COX-1/COX-2 >1, the drug is more specific for COX-2
12
Q
COX-1 _______
COX-1 ______ ( _____ selective)
COX-2 _____
COX-2 _______
COX-2 ________ (______ selectivity)
A
selective, sparing, Non, specific, selective, preferential, limited
13
Q
Potential benefits in inhibiting LOX pathway:
A
▪ Higher GI safety
▪ Greater analgesic efficacy
14
Q
List the examples of Dual inhibitors:
A
Benoxaprofen
Ketoprofen
Licofelone
Corticosteroids (adverse effects)
Tepoxalin (Zubrin) is approved in Europe and USA
in animals (osteoarthritis in dogs)
15
Q
List the NSAIDs that fall under the category of the following:
- Selective COX-1 inhibitor
- Non-selective COX inhibitors
- Selective COX-2 Inhibitors
- Dual Inhibitors - COX/LOX
A
See below
16
Q
Selective COX-1 Inhibitors
A
Low-dose Aspirin
17
Q
Non-selective COX Inhibitors
A
FAKIN
- Naproxen (AleveR)
- Ibuprofen (MotrinR, AdvilR)
- Ketoprofen ((AnafenR)
- Aspirin
- Flunixin meglumine
18
Q
Selective-COX-2 Inhibitors
A
19
Q
Dual Inhibitors COX / LOX
A
Tepoxalin
20
Q
Adverse effects of NSAIDs
A
21
Q
NS –> Aspirin - Dogs
A
Aspirin is not USDA –registered for dogs, but some forms are marketed
for dogs as if there were FDA approval. There is an approved combination
with methylprednisolone (Cortaba tablets)
22
Q
COX-2 Inh for dogs?
A
Pneumonic:
Christine Eats Many Penises
23
Q
______________ is Registered for dogs but not actively marketed
A
Phenylbutazone
24
Q
Carprofen (________) Available as an ____________ and ____ (COX-___ sparing in dogs)
A
Rimadyl, injectable, oral, 1
25
Meloxicam (_______) is Registered for cats also as a ___ dose, available as an _____ and __
Metacam, single, injectable, oral
26
The NS Ketoprofen (Anafen) is registered for ?
cats only
27
Deracoxib (_________) is (COX-__ ______, first veterinary drug in this group)
Deramaxx, 2, specific
28
_________ _______ (Arquel) is _______ but not marketed
Meclofenamic acid, registered
29
__________ ____ (Tolfedine) is registered in ______ only, available as an ______ and ___
Tolfenamic acid, Canada, injectable, oral
30
Aspirin is a NSAID used to reduce?
Pain
Fever
Inflammation
Platelet aggregation
31
Aspirin: (low doses) prevents?
heart attacks and strokes.
32
Salicylic acid from _____ ____ have been used for ____ relief since ancient times
willow, bark, pain
33
Modification of Salicylic acid to ______ ________ ______ (____) = Aspirin
Acetyl Salicylic Acid (ASA)
34
Use of aspirin for pain and prevention of myocardial infarction
▪ Understanding the molecular mechanism of aspirin
35
Aspirin MOA
Aspirin irreversible inhibits COX-1 resulting in
decreased PG synthesis
decrease TXA2 expression
36
Effects of Aspirin
Analgesic
Antipyretic
Anticoagulant: platelet aggregation reducer
Anti-inflammatory: PGs expression reducer
37
Asprin PK:
Absorption from the _____ and ___ intestine
Bound to _____ (70-90%)
_____ t1/2 in cats (~30 hrs); in dogs (~ 8 hrs); in horses (~ 5 hrs)
_____ are sensitive to aspirin toxicity _____ are sensitive to GI effects (bleeding)
stomach, upper, albumin, Long, Cats, Dogs
38
______ are sensitive to aspirin toxicity
Cats
39
_____ are sensitive to GI effects (bleeding)
Dogs
40
Adverse effects of Asprin:
▪ GI distress: ?
▪ Paradoxical-_______ (body T above ______ F (____ C)
▪ _____ventilation, respiratory _____ (_____ depression)
▪ Metabolic ______
▪ ___________
▪ Pulmonary ______ (______)
▪ If chronic use ----- _________ during surgery
▪ In dogs with _____, long-term use may result in aggravation of joint disease
▪ Drug-drug interaction (_______)
vomiting, anorexia, GI ulceration, diarrhea
hyperpyrexia, 106.70, 41.50, Hyper, acidosis, CNS, acidosis, Dehydration, edema, sheep, bleeding, OA, Warfarin
41
Treatment of aspirin-toxicity:
▪ Induce ______ in the case of ____ toxicity
▪ Increase _____ of the drug: gastric lavage followed by administration of activated _____
▪ Increase _____ excretion of aspirin by administrating an ______ agent
▪ Initiate IV ___ therapy to address _____ and metabolic ______
emesis, acute, removal, charcoal, urinary, alkalinizing, fluid, dehydration, acidosis
42
Aspirin
Contraindications: Patients with _____ GI ______; _______ disorders, _____, or _____ insufficiency
active, bleeds, bleeding, asthma, renal
43
Flunixin meglumie AKA?
Banamine
44
Flunixin: A _____-_________ COX inhibitor with potent __________ and ______-___________ effects
non-selective, analgesic, anti-inflammatory
45
MOA of Flunixin meglumine
MOA: Shows greater COX-2 inhibitory effects than COX-1 in _________-.
In _________-, it appears to exhibit preferential COX-1 inhibitory effect
MOA: Shows greater COX-2 inhibitory effects than COX-1 in horses.
In dogs, it appears to exhibit preferential COX-1 inhibitory effect
46
Uses of Flunixin meglumine
Uses:
▪ For the treatment of ____, ______, and _______ pain
▪ Exceptional property: it alleviates ________ pain related to colic
▪ In horses: effective in producing the _________ duration of ________ analgesia (~ ___ hrs)
▪ In cattle: for the control of _________ associated with respiratory disease, _________ and _______ (____ approved by FDA)
Uses:
▪ For the treatment of acute, visceral, and surgical pain
▪ Exceptional property: it alleviates visceral pain related to colic
▪ In horses: effective in producing the longest duration of postoperative analgesia (~ 13 hrs)
▪ In cattle: for the control of pyrexia associated with respiratory disease,
endotoxemia and mastitis (not approved by FDA)
47
PK for Flunixin meglumine
PK:
▪ Administered via what routes:
▪ IV: a plasma t1/2 of 2-4 hrs (______); 3-6 hrs (____); 4hrs (____);1-1.5 hrs (____)
▪ IV: Duration of action is ___-____ hrs
▪ _____ excretion
IV, IM, horses, cattle, dogs, cats, 24-36, Renal
48
Adverse Effects - Flunixin Meglumine
Adverse effects:
▪ _________ with IM administration
▪ Overdose in horses: ulcers on the ?, _____ depression, _______ (rare)
▪ In dogs: _____ failure and ___ damage
Adverse effects:
▪ Myonecrosis with IM
▪ Overdose in horses: ulcers on the tongue, gingiva, lips, and stomach
CNS depression, anorexia (rare)
▪ In dogs: renal failure and GI damage
49
Ketoprofen: A ____-_______ COX inhibitor with ___-_________ and _______ effects
non-selective, anti-inflammatory, analgesic
50
Ketoprofen MOA
MOA: Inhibition of COX-1 and COX-2 and LOX-pathway ( LTB4 synthesis)
51
List the uses of Ketoprofen
Uses: In horses:
▪ Acute and chronic ___________ disorders
PK:
▪ Admin routes?
▪ Excellent bioavailability of ___-___%
▪ _____ elimination t1/2 of ~ 1 hr (horses); 1.5 hrs (dogs and cats)
▪ _____ excretion
Uses: In horses:
▪ Acute and chronic musculoskeletal disorders
PK:
▪ IV, IM, SC or PO
▪ Excellent bioavailability of 80-100%
▪ Short elimination t1/2 of ~ 1 hr (horses); 1.5 hrs (dogs and cats)
▪ Renal excretion
52
Adverse effects of Ketoprofen?
Adverse effects:
▪ Safer profile compared to _____ or _________
▪ PO: GI injury including ______ and ______
▪ Caution in animals with ________ disorders (decreased platelet _______)
▪ Caution in animals with compromised _____ function
flunixin, phenylbutazone, ulceration, bleeding, hemostatic, aggregation, renal
53
Phenylbutazone: The _____ and _____ profile in addition to its _____
makes it the most commonly used NSAID in the ____
safety, efficacy, affordability, horse
54
Phenylbutazone MOA
Preferential COX-___ inhibitor in both ____ and ___
MOA: Preferential COX-2 inhibitor in both horses and dogs
55
Phenylbutazone Uses
Uses:
▪ Osteoarthritis
▪ Various forms of lameness
▪ Rheumatism
▪ Other painful conditions of the limbs
▪ Nonspecific inflammation in other conditions
56
Phenylbutazone PK
PK:
▪ After IV administration, t1/2 is ____-_____ hrs in the dog and horse
▪ Long duration of action (___-___ hrs)
▪ ______ metabolite (___________)
▪ High ______ binding
▪ Elimination via ____ excretion (25%)
PK:
▪ After IV administration, t1/2 is 2,5 – 6 hrs in the dog and horse
▪ Long duration of action (24 -72 hrs)
▪ Active metabolite (oxyphenylbutazone)
▪ High albumin binding
▪ Elimination via renal excretion (25%)
57
Adverse effects of Phenylbutazone
▪ GI distress: ?
▪ Renal papillary _______
▪ ________ (hypovolemic shock, ulcer-mediated sepsis)
Adverse effects:
▪ GI distress: erosions, ulcers, anorexia, colic, diarrhea
▪ Renal papillary necrosis
▪ Death (hypovolemic shock, ulcer-mediated sepsis
58
Contraindications of Phenylbutazone
Contraindications: Patients with serious cardiac, renal, hepatic injury, or hematologic disorder
59
Carprofen: preferential COX-___ inhibitor with _____ and ____-_____ effects
2, analgesic, anti-inflammatory
60
Carprofen MOA
Potency of carprofen for canine COX-___ is more than ______- fold greater relative to canine COX-___
MOA: Potency of carprofen for canine COX-2 is more than 100- fold greater relative to canine COX-1
61
Carprofen Uses
1. _____-term and _____-term pain management
2. ______________ disorders
Uses: Short-term and long-term pain management
▪ Musculoskeletal disorders
62
Carprofen PK
▪ Administrated via ?
▪ PO: the Tmax is short or long?
▪ Highly bound to _______ (99%)
▪ ______ metabolism
▪ Eliminated in the _____ and ______
▪ Elimination t1/2 in cats: ?
in dogs: ?
PK:
▪ PO, IV or SC
▪ PO: the Tmax is 1-3 hrs (dogs) SHORT
▪ Highly bound to albumin (99%)
▪ Liver metabolism
▪ Eliminated in the feces/urine
▪ Elimination t1/2 in cats: ~ 20 hrs LONG
in dogs: ~ 5-7 hrs MIDDLE GROUND?
63
Carofen adverse effects
▪ Lower frequency of GI ______ and ______
▪ ___________, __________, __________
▪ Caution in patients with _____ or ____ dysfunction
Adverse effects:
▪ Lower frequency of GI ulceration and hemorrhage
▪ Diarrhea, anorexia, vomiting
▪ Caution in patients with hepatic or renal dysfunction
64
Carprofen contraindications
Contraindications: Patients with hemostatic disorders; pregnant, lactating, or breeding bitches
65
Meloxicam aka?
Metacam
66
Meloxicam: A preferential COX-______ inhibitor with __________ and ____-________ effects
2, analgesic, anti-inflammatory
67
Meloxicam MOA
MOA: COX2/COX1 selectivity ratio of ~ 10
68
Meloxicam Uses
Uses: For treatment of chronic ____ and ________
▪ _______________
▪ ______-operative ______ pain
Uses: For treatment of chronic pain and inflammation
▪ Osteoarthritis
▪ Post-operative somatic pain
69
Meloxicam PK
▪ PO: ______ absorption, Tmax ~ ___ hrs
▪ _______ bound to albumin (97%)
▪ The plasma t1/2 is ______-specific: 12-24 hrs (____); 15 hrs (____); 3 hr (_______)
▪ ______ metabolism
▪ Elimination in the ____
PK:
▪ PO: good absorption, Tmax ~ 8 hrs
▪ Highly bound tp labumin (97%)
▪ The plasma t1/2 is species-specific: 12-24 hrs (dogs); 15 hrs (cats); 3 hr (horses)
▪ Liver metabolism
▪ Elimination in the feces
70
Meloxicam Adverse effects
___________ safe NSAID in dogs and cats
▪ ___ distress
▪ _________
▪ _______
^ all of the above are ____ and _____
Adverse effects:
Relatively safe NSAID in dogs and cats
▪ GI distress
▪ Anemia
▪ lethargy
Rare and transient
71
Repeated use of Meloxicam in cats can evoke ______ ______ failure and _____
Caution: Repeated use in cats can evoke acute renal failure and death
72
Meloxicam contraindications
Contraindications: Not recommended in pregnant, lactating or in young animals (< 4 months)
73
Meloxicam is FDA-approved in ______.
cats
74
Etodolac: A preferential COX-____ inhibitor with ______ and ____-________ effects
2, analgesic, anti-inflammatory
75
Etodolac MOA
?
76
Etodolac AKA
EtoGesic
77
Etodolac Uses
▪ _____________ in dogs
▪ Other conditions
▪ Osteoarthritis in dogs
▪ Other conditions
78
Etodolac PK
▪ PO: ______ absorption and a _____
onset of action (30-60 min)
▪ Is the half life long or short?
▪ ____ excretion
▪ PO: Rapid absorption and a rapid
onset of action (30-60 min)
▪ Long plasma t1/2 : 10-14 hrs
▪ Bile excretion
79
Etodolac Adverse effects:
____ distress
______ depression
______totoxicity
_______toxicity
May induce ________________ _____ in dogs (monitor ____ production)
GI distress , CNS depression, hepatotoxicity, nephrotoxicity
May induce keratoconjunctivitis sicca in dogs (monitor tear production)
80
Etodolac caution
Caution: In patients with hematological, renal, or hepatic impairment
81
Tepoxalin: _____ inhibitor: _____-_______ COX inhibitor plus potent inhibitory effect on _____
Dual, non-selective, LOX
82
Tepoxalin AKA
Zubrin
83
Tepoxalin MOA
MOA: inhibition of COX-__, COX-___, and ___-LOX
reduction of the production of ____ mediators of pain, fever, and inflammation
MOA: inhibition of COX-1, COX-2, and 5-LOX
reduction of the production of PG mediators of pain, fever, and inflammatio
84
Tepoxalin uses
▪ __________ in dogs
▪ _______ conditions in dogs
▪ ____- operative pain control
▪ Osteoarthritis in dogs
▪ Allergic conditions in dogs
▪ Postoperative pain control
85
Tepoxalin PK
▪ Readily absorbed after _____
▪ _______ metabolized, one ____ metabolite, Both are highly bound to ______
▪ T1/2: __ hrs and __ hrs, respectively
▪ Elimination in the ______
▪ Readily absorbed after PO
▪ Rapidly metabolized, one active metabolite
▪ Both are highly bound to albumin
▪ T1/2: 2 hrs and 13 hrs, respectively
▪ Elimination in the feces
86
Tepoxalin Adverse effects
▪ GI distress: vomiting, anorexia, diarrhea, ulceration
▪ CNS depression
▪ Hepatotoxicity
▪ Nephrotoxicity
87
Deracoxib (DeramaxxR) Uses
▪ Osteoarthritis
▪ Post-operative pain and inflammation
88
Deracoxib PK
▪ PO:
▪ _____ protein bound
▪ _____ excretion
▪ 20% may be excreted in the _____
▪ PO:
▪ Highly protein bound
▪ Bile excretion
▪ 20% may be excreted in the urine
89
Deracoxib adverse effects
GI distress
90
Firocoxib is also called ?
PrevicoxR, Equioxx
91
Firocoxib uses?
Osteoarthritis
92
Firocoxib PK
▪ The bioavailability: ~ 80% in _______
~ 40% in ___
▪ ______ protein bound
▪ _______ metabolism
▪ _____ excretion
▪ The bioavailability: ~ 80% in horses
~ 40% in dogs
▪ Highly protein bound
▪ Hepatic metabolism
▪ Fecal excretion
93
Firocoxib adverse effects
▪ Diarrhea, mouth ulcers
▪ Excitation (rare)
^ horses
▪ Vacuolization in the brain
(high doses)
^ dogs
94
Drugs that are rarely used in Veterinary Medicine
Non-selective COX Inhibitors:
Aspirin
Acetaminophen (TylenolR) ( particularly unsafe in cats)
(paracetamol)
Ibuprofen (Motrin, Advil)
Naproxen (Aleve) (used in horses to treat myositis, lameness)
Indomethacin
95
Dimethyl sulfoxide (DMSO): a solvent for many _____, ____ and _____ compounds. It is clear, _____ to ____-yellow liquid, highly _______.
aromatic, organic, inorganic, colorless, straw, hygroscopic
96
Dimethyl sulfoxide (DMSO) effects
▪ Anti-inflammatory: inhibits PG synthesis and traps free radicals
▪ Analgesic
▪ Skin penetrating
▪ Diuretic
▪ Anticholinesterase
▪ Weak antibacterial
▪ Weak antifungal
97
Dimethyl sulfoxide (DMSO) PK
▪ Well absorbed after _______ application
▪ _________ & ______ distribution
▪ Primarily _____ excretion
▪ Well absorbed after topical application
▪ Extensive & rapid distribution
▪ Primarily renal excretion
98
Dimethyl sulfoxide (DMSO) Uses
▪ _____ swelling (_________ trauma)
▪ Cerebral _____ & ______ (spinal cord trauma)
▪ _________ (urethral ________ in the cat)
▪ Superficial _____
▪ Skin _____
▪ Transient ______ conditions
▪ Edema of limbs resulting from _____
▪ _____ and _______ of mammary glands in the nursing bitch
▪ Severe __________ resulting from the extravascular injection of irritating drugs or lick granuloma
▪ Acute swelling (musculoskeletal trauma)
▪ Cerebral edema & paralysis (spinal cord trauma)
▪ Cystitis (urethral obstruction in the cat)
▪ Superficial burns
▪ Skin grafts
▪ Transient ischemic conditions
▪ Edema of limbs resulting from fractures
▪ Swelling and engorgement of mammary glands in the nursing bitch
▪ Severe inflammation resulting from the extravascular injection of irritating drugs or lick granuloma
99
Dimethyl sulfoxide (DMSO) adverse effects
When used as labeled, it is _____
▪ Transient _____ effects
▪ High doses, long use ---- ______
▪ IV: _______ and ________
▪ _____ and ____ damages, pulmonary ____
▪ CNS: _______, _________, ________
When used as labeled, it is safe
▪ Transient local effects
▪ High doses, long use ---- myopia
▪ IV: hemolysis and hemoglobinuria
▪ Hepatic and renal damages, pulmonary edema
▪ CNS: sedation, coma, seizures
100
OA is a degenerative joint disease that affects the dog’s spine and lower limbs leading
to stiffness and excruciating pain in the joint
101
Synovial lining is a membrane surrounding each joint, SF
(synovial fluid) helps ensure smoot and easy body movement
Hyaluronic acid (HA) is a natural lubricant of the joints, part of
SF.
102
Polysulfated glycosaminoglycan :
Disease-modifying osteoarthritis drugs (DMOADs)
(AdequanR) (PSGAG)
103
PSGAG MOA
▪ PSGAG modulates clinical signs of ______ by indirectly promoting ______________ effect via different mechanism
▪ Improves joint articular function by having effects on _________ _____
▪ Anti-inflammatory: inhibition of _____ biosynthesis, ________ migration & ________ levels
▪ PSGAG modulates clinical signs of OA by indirectly promoting chondroprotective effect
via different mechanism
▪ Improves joint articular function by having effects on synovial fluid
▪ Anti-inflammatory: inhibition of PGE2 biosynthesis, leukocyte migration & interleukin levels
104
PSGAG Uses
▪ To treat traumatic joint dysfunction (horses)
▪ To treat OA and prevent hip dysplasia (dogs)
105
PSGAG PK
route: Intra-articularly (IA) or IM
▪ No information is available
106
PSGAG Adverse Effects
When used as labeled, it is safe
Associated with drug administration, i.e. / septic arthritis
Polysulfated glycosaminoglycan (PSGAG)
107
Hyaluronate sodium (HS)
MOA?
A cushioning effect: reducing cell ________
Lubricating effect on the _______ ___ tissue
A scavenging effect: removes ____-derived free radicals
A cushioning effect: reducing cell migration
Lubricating effect on the articular soft tissue
A scavenging effect: removes O2-derived free radicals
108
Hyaluronate sodium Uses?
Uses: To treat _______ that is associated with OA in dogs and horses
PK: No information is available in _____
Adverse effects: Transient ____ effects: ?
Uses: To treat synovitis that is associated with OA in dogs and horses
PK: No information is available in animals
Adverse effects: Transient local effects: swelling, heat
109
Hyaluronate sodium PK
PK: No information is available in animals
110
Hyaluronate sodium Adverse effects
Adverse effects: Transient local effects: swelling, heat
111
Guidelines for the safe use of NSAIDs
▪ Individualized dosage based on the drug’s ________, ____ of the animal, and _________ of action
▪ Screen patients for underlying ______ and _______ dysfunction by performing ________ diagnostic procedures
▪ Monitor the _________ status of patients. __________ animals should not be places on NSAIDs before the hydration status is improved
▪ An adequate ______ ______ period should be allowed prior administrating a new NSAID
▪ Administer the _______ possible effective dose for the ______ period to minimize risk of injury
▪ Concurrent use of __________ and _______ should be avoided due to increased risk of GI complications
Guidelines for the safe use of NSAIDs
▪ Individualized dosage based on the drug’s efficacy, age of the animal, and duration of action
▪ Screen patients for underlying renal and hepatic dysfunction by performing routine diagnostic
procedures
▪ Monitor the hydration status of patients. Hypovolemic animals should not be places on NSAIDs
before the hydration status is improved
▪ An adequate wash out period should be allowed prior administrating a new NSAID
▪ Administer the lowest possible effective dose for the shortest period to minimize risk of injury
▪ Concurrent use of glucocorticoids and NSAIDs should be avoided due to increased risk of
GI complications
