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Pharmacology II > LEC 6 - Nonopioid Analgesics > Flashcards

LEC 6 - Nonopioid Analgesics Flashcards

1
Q

What are the four signs of inflammation?

A

Erythema + Edema + Tenderness + Pain

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2
Q

What are the three phases of inflammation?

A

Acute inflammation

Immune response

Chronic inflammation

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3
Q

What are the five mediators of acute inflammation?

A

Histamine

Serotonin

Bradykinin

Prostaglandin

Leukotrine

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4
Q

What are the four effects of the acute inflammatory mediators?

A

Vasodilation

Vascular permeability

Chemotaxis

Pain

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5
Q

Effects: Histamine

A

Vasodilation ++

Vascular Permeability +++

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6
Q

Effects: Serotonin

A

Vasodilation +/-

Vascular permeability +

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7
Q

Effects: Bradykinin

A

Vasodilation +++

Vascular permeability +

Pain +++

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8
Q

Effects Prostaglandin

A

Vasodilation +++

Vascular Permeabiltiy +

Chemotaxis +++

Pain +

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9
Q

Effects: Leukotrines

A

Vascular permeability +++

Chemotaxis +++

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10
Q

What is the precursor to LT’s + PG’s?

A

Arachodonic Acid

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11
Q

What makes LTs?

A

Lipoxygenases

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12
Q

What makes prostaglandins?

A

COX 1/2

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13
Q

What is the structure of prostaglandins?

A

Oxygenation products of polyunsaturated long chain FA’s

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14
Q

How does arachodonic acid leave the membrane?

A

Via phospholipase A2

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15
Q

Characteristic: COX-1

A

Constitutively expressed

Housekeeping functions

Widely distributed

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16
Q

Characteristics: COX-2

A

Inducible

Depends on stimulus

Immediate early response gene

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17
Q

What are the main functions of the products made by COX-2?

A

Stimulate growth factors

Tumor promoters

Cytokines

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18
Q

What is COX-2 mainly responsible for?

A

Prostacylcin in endothelial cells

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19
Q

Describe the mechanism by which Asprin Asthma occurs?

A

NSAID blocks COX enxymes = decrease in PG’s

Increase A. Acid that gets shuttled to Lipoxygenase path

Increased production of Leukotrines

= Increase broncoconstirction + congestion + mucous plugging

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20
Q

Mechanism: Asprin/ASA/Acetylsalicyclic acid

A

Nonselective, irreversible inhibitor of COX-1/2

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21
Q

Asprin - Effects

A

Analgesic

Antipyretic

Anti-inflammatory

Platelet

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22
Q

Describe: Asprin’s analgesic effects

A

Low intensity pain

Pain from integumental structures

Due to peripherial + CNS effects

Prevents sensitization of pain receptros to stimuli

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23
Q

How does asprin act locally?

A

Hypothalmic area to reduce fevers

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24
Q

When does asprin not work?

A

As an analgesic in non-inflammed painful conditions

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25
When is aspirin successful at lowering temperature?
Febrile patients Fever due to inflammation + infection + tissue damage
26
By what mechanism does aspirin reduce fever?
Resetting the thermostat to normal body temp Therefore problem needs to be within the hypothalamus
27
Aspirin - Distribution
Throughout body tissues + ETC compartments Crosses placenta Slowly crosses BBB
28
Aspirin - Metabolism
Hydrolyzed = Plasma + Liver + Erythrocytes Salicylic acid - Glucuronidated in liver
29
Aspirin - Elimination
Kidney
30
Aspirin - Half lives Dog Cat Horse
8 hours - dog 38 hours - cat 30 min - horse
31
Aspirin - Protein Binding
Plasma protein - 50 ot 90%
32
Aspirin - Adverse Effects
GI upset Paradoxical hyperpyrexia Dehydration Pulmonary edema in sheep
33
What happens in canines with chronic asprin use?
Canine chondrocytes are sensitive to COX-1 inhibition Aggrevation of canine joint disease
34
How long before surgery must asprin be discontinuesd?
7 days
35
How does aspirin cause hyperpyrexia?
uncoupling of oxidative phosphorylation
36
How does asprin cause acid-base disturbances?
1- Alkalosis via stimulation of medullary respiratory center = hyperventilation 2 - Acidosis due to CNS depression
37
How does aspirin cause pulmonary edema in sheep?
Imbalance of vasodilatory PG's + Vasocontrictive PG's Increased vascular permeability
38
Aspirin - Administration
Oral
39
Aspirin - Uses
Adjunct therapy for septic + endotoxic shock
40
Aspirin - Contraindicated treatment
OA Colic
41
Aspirin - Drug interactions
Due to salicylate-mediated displacement of other drugs that compete for same albulmin binding site Warfarin Throxin T3 Penicillin Thiopental Bilirubin Phenytonin Naproxen
42
How do you treat aspirin toxicity?
Induce vomiting Increase removal of drug - gastric lavage + activated charcoal Increase urinary excretion - alkalinizing agent IV fluids
43
NSAID's pharmodynamics (effects)
Anti-inflammatory Analgesic Antipyretic Platelet effects
44
Describe the effects NSAID's have on platelets
Irreversible inhibition of platelet COX enzymes Cannot synthesize new ones
45
How long do platelet effects from NSAID's last?
8 to 10 days
46
Describe NSAID Toxicity
GI - pain + bleeding + pancreatitis CNS - confusion + depression + dizzy Lung - bronchoconstriction Bone marrow - argranulocytosis + aplastic anemia Nephrotoxicity - renal failure + intersitial nephritis + nephrotic syndrome Heptaotoxicity Hypersensitivity
47
Phenylbutazone - Mechanism of Action
Preferential COX-2 inhibitor Horses + Dogs
48
Phenylbutazone - Admin
PO +IV
49
Phenylbutazone - use
Lameness + OA Soft tissue pain Nonarticular rheumatism
50
Phenylbutazone - Duration of action
24 to 72 hours
51
Why is phenylbutazone so long action?
Irreversible binding
52
Phenylbutazone - Protein binding
99% High plasma protein bdingin
53
Phenylbutazone - Metabolism
Almost complete in Horse
54
Phenylbutazone - Elimination
25% via renal over 24 hours
55
What effect does phenylbutazone have on microsomal enzymes?
Induces the production of = lower plasma levels of drug with chronic administation also leads to drug interactions
56
Phenylbutazone - Adverse effects
Renal papillary necrosis Petechial hemorrhages Ulcers Hypoproteinemia
57
Phenylbutazone - Food animals
not to be given to dairy cattel \> 20m of age NO USE IN FOOD ANIMALS
58
Phenylbutazone - Cause of Death
Protein losing enteropathy = Decrease in blood volume + hemoconcentration + hypovolemic shock + circulatory collapse
59
Phenylbutazone - Contraindications
Not to be given to patients with: Cardiac/renal/hepatic disease Hematocytologic disorder
60
Flunixin meglumine - Indicated treatment
Acute + VISCERAL + Surgical pain
61
Flunixin meglumine - Mechanism of action
COX-2 \> COX-1 in horse COX - 1 \> COX-2 in dogs
62
Flunixin meglumine - Contraindications
EGGUS - horses
63
Flunixin meglumine - ADMIN
IV + IM
64
Flunixin meglumine - Withdrawl times
4 days pre-slaughter 36 hours milk
65
Flunixin meglumine - Adverse effects
Hypersensitivity in cattle
66
Flunixin meglumine - BA
80% with PO admin
67
Flunixin meglumine - Plasma protein binding Cows Dogs Horses
Cows - 99% Dogs - 92% Horses - 87%
68
Flunixin meglumine - 1/2 life Horse Cattle Dog Cats
Horse - 2 to 4 hours Cattle - 3 to 8 hours Dogs - 4 hours Cats - 1 to 1.5 hours
69
Flunixin meglumine - Excretion
Renal
70
Naproxen - Use
Horses with soft tissue pain Inflammatory swelling with lameness
71
Naproxen - 1/2 life
4 hours = horses
72
Naproxen - Time to see effect
5 to 7 days
73
Naproxen - metabolism
Glucoronidation - liver
74
Naproxen - Excretion
Urine \> 48 hours
75
Naproxen - Mechanism
Non-selective COX inhibitor
76
Ketoprofen - Mechanism
Non-selective inhibitor of COX Blocks LTB4 synthessis
77
Ketoprofen - Target
Sequestered at site of inflammation | (inflamed synovial joint)
78
Ketoprofen - Admin
IV + IM + SC + PO
79
Ketoprofen - BA Horses Dogs/Cats
Horses = ~ 1 hour Dogs/Cats = 1.5 hours
80
Ketoprofen - Eliminated
Kidneys
81
Ketoprofen - Adverse effects
Safer then phenylbutazone + flunixin
82
Ketoprofen - use
Horses alleviation of inflammation + pain for acute/chronic musculoskeletal disorders
83
Ketoprofen - Food animals
NOT ALLOWED
84
Carprofen - Mechanism
Preferential COX-2 inhibitor
85
Carprofen - Admin
PO + IV + CS
86
Carprofen - Use
Analgesic + Anti-inflammatory in dogs
87
Carprofen - 1/2 life
5 to 9 hours
88
Carprofen - BA
90% with PO dose
89
Carprofen - Protein binding
Bound to albulmin 99%
90
Carprofen - Metabolism
Liver via Oxidation then glucoronidation
91
Carprofen - Elimination
Feces (70 to 80%) Urine
92
Carprofen - Adverse effects
Lower GI problems due to COX-2 target
93
Carprofen - Contraindication in Cats
Increased risk of renal disease
94
What are the COX-2 inhibitors?
Deracoxib Robencoxib Firocoxib
95
Deracoxib - Indications
Pain + Inflammation in OA = Dogs
96
Robenacoxib - Indications
Musculoskeletal disorders + soft-tissue surgeries in cats
97
Firocoxib - Indications
Pain + Inflammation - OA Postoperative pain
98
Firocoxib - Admin
Oral paste - Horses Tablets - Dogs
99
Meloxicam - Mechanism
preferential COX-2 inhibitor
100
Meloxicam - use
Chronic pain + inflammation with OA = dogs/cats
101
Meloxicam - Absorption
Well absorbed Food does not altered
102
Meloxicam - Protein binding
97% boudn to albulmin
103
Meloxicam - Metabolism
Liver - glucuronide conjugates
104
Meloxicam - 1/2 life Dogs Cats
Dogs = 12 to 24 hours Cats = 15 hours
105
Meloxicam - Elimination
Feces via enteroheptatic recirculation
106
Meloxicam - Adverse effects in cats
Repeated use = AKI + Death
107
Acetaminophen - Cats contraindication
Deficiency in glucuronyl transferase Makes them susceptible to metHg + centrilobular hepatic necrosis

Pharmacology II (20 decks)

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