LEC 6 - Nonopioid Analgesics Flashcards Preview

Pharmacology II > LEC 6 - Nonopioid Analgesics > Flashcards

Flashcards in LEC 6 - Nonopioid Analgesics Deck (107):
1

What are the four signs of inflammation?

Erythema + Edema + Tenderness + Pain

2

What are the three phases of inflammation?

Acute inflammation 

Immune response 

Chronic inflammation 

3

What are the five mediators of acute inflammation?

Histamine 

Serotonin 

Bradykinin 

Prostaglandin

Leukotrine

4

What are the four effects of the acute inflammatory mediators?

Vasodilation 

Vascular permeability 

Chemotaxis 

Pain 

5

Effects: Histamine

Vasodilation ++ 

Vascular Permeability +++

6

Effects: Serotonin

Vasodilation +/- 

Vascular permeability +

 

7

Effects: Bradykinin 

Vasodilation +++

Vascular permeability + 

Pain +++ 

8

Effects Prostaglandin

Vasodilation +++

Vascular Permeabiltiy + 

Chemotaxis +++ 

Pain + 

9

Effects: Leukotrines

Vascular permeability +++

Chemotaxis +++ 

10

What is the precursor to LT's + PG's?

Arachodonic Acid 

11

What makes LTs?

Lipoxygenases 

12

What makes prostaglandins?

COX 1/2 

13

What is the structure of prostaglandins?

Oxygenation products of polyunsaturated long chain FA's 

14

How does arachodonic acid leave the membrane?

Via phospholipase A2

15

Characteristic: COX-1

Constitutively expressed 

Housekeeping functions 

Widely distributed 

16

Characteristics: COX-2

Inducible 

Depends on stimulus 

Immediate early response gene

17

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

Stimulate growth factors 

Tumor promoters 

Cytokines 

18

What is COX-2 mainly responsible for?

Prostacylcin in endothelial cells 

19

Describe the mechanism by which Asprin Asthma occurs?

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

20

Mechanism: Asprin/ASA/Acetylsalicyclic acid 

Nonselective, irreversible inhibitor of COX-1/2 

21

Asprin - Effects

Analgesic 

Antipyretic 

Anti-inflammatory 

Platelet 

22

Describe: Asprin's analgesic effects

Low intensity pain 

Pain from integumental structures 

Due to peripherial + CNS effects 

Prevents sensitization of pain receptros to stimuli

23

How does asprin act locally?

Hypothalmic area to reduce fevers

24

When does asprin not work?

As an analgesic in non-inflammed painful conditions 

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