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PHARMACOLOGY > Unit 4 - Anti-Inflammatories > Flashcards

Unit 4 - Anti-Inflammatories Flashcards

1
Q

What is inflammation?

A

normal response to trauma, infection , neoplasia as first stage of tissue repair
Part of innate immune system - non-specific, will damage surrounding healthy tissue
5 hallmarks of inflam PRISH
pain (inflam mediators
Redness (vasodilation
Immobilization/loss of function
Swelling (edema)
Heat

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2
Q

What are the 4 steps to the pain pathway?

A
  1. transduction - noxious stimuli (chemical, thermal, mechanical) are transformed into electrical signals
  2. Transmission - conduction of impulses from peripheral pain receptors to spinal cord
  3. modulation - amplification or suppression of pain impulses by neurons in the spinal cord
  4. perception - processing and recognition of pain in the prain
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3
Q

What is the arachidonic acid pathway

A

Tissue injury occures w/ cytokins and histamines and makes phospholipase. This breaks down cell membrane phospholipid into arachidonic acid
2 pathways
1. Cyclooxygenase (COX) to prostaglandins for pro-inflam), thromboxane (activates platelets)
2. Lipoxygenase (LOX) leukotrienes which can activate and/or inhib diff types of WBCs

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4
Q

What is the function of prostaglandings in inflam?

A

prod signs of inflam by causing;
vasodilation (inc blood flow)
smooth muscle contraction (edema, bronchoconstriction)
Heat, fever
pain @ site of injury
protective action on the GIT wall, balance stomach pH thru secretion of bicarb and inc mucus prod

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5
Q

What is the function of thromboxane? Leukotrienes?

A

Thromboxane - platelet activation > clotting
Leukotrienes - chemotaxis (attracts) WBCs, activates WBCs, inc vascular permeability (involved in vasodilation during anaphylaxis), bronchspasm

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6
Q

What is the mechanism of anti-inflammators

A

Turn down inflam by blocking arachidonic acid pathway
Antihistamines to prevent histamines releasing phospholipase
Steroids block phospholipase
COX blocked by NSAIDS

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7
Q

What are the 2 major classes to tx inflammation ?

A
  1. steroids
  2. non-steroidal anti-inflammations
  3. (anti-histamines0
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8
Q

What are steroids?

A

called exogenous steroids
act the same as endogenous steroids which are naturally prod by adrenal glands
both exo/endo are part of feedback loop in hypothalamic-pituitary-adrenal axis (HPA axis)

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9
Q

What are exogenous steroids?

A

steroid drugs
cause use as anti-inflame (similar to NSAIDS at low dose) - dex inflam, mild to mod pain control, does not control fever producing cytokines
@higher doses can be used to manage shock and have immunosuppressive effects
Longer-acting than NSAIDS; up to 4mo after single dose depending on which drug

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10
Q

What are the physiological effects of steroids

A

involved in metabolism, electrolyte control, sex function
glucocorticoids - affect glucose, protein and fat metabolism, inhib inflam, fibrocytes, platelets (low dose), suppresses lymphocytes (high dose), enhances/maximizes fight-or-flight response, dec prostaglandin-mediated sensation of pain
Mineralocorticoids - controls water and electrolyte distribution, no influence on the immune system,
most exogenous steroids are glucocorticords

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11
Q

How do steroids stop inflammation?

A

inhibit phospholipase and (to a lesser extentW) cyclooxygenase (COX)
inhib prod of prostaglandins, thromboxane and leukotrienes

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12
Q

hat are the most common clinical indications for steroids?

A
  1. anti-inflam @ low dose: eye, ear, arthritis (joint injections), asthma
  2. Immune suppressant @ high dose
  3. Analgesic
  4. Other: appetite, stimulant, palliation of lymphosarcoma and mast cell tumors (suppresses lymphocytes and inflam), treating proud flesh (inhibs inflam, platelets and fibrocytes), addison’s dz (hypoadrenocorticism)- releases endogenous steroids
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13
Q

What are the adverse effects of local steroids?

A

topical formulas rarely cause systemic effects
chronic use of eye drops can cause thinning of cornea - don’t use if cornea ulcered
chronic use on skin can cause thinning of skin and dec healing
inhaled steroids can result in some systemic signs

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14
Q

What are some less concerning side effects of steroids?

A

almost always occur, but not concerning. Do warn owners
1. Polyphagia - eat more
2. PU/PD - may cause owners to complain about inappropriate urination
3. Panting - common in dogs

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15
Q

What are some adverse effects for short-term steroids?

A
  1. GI Upset (V/D)
  2. GI ulceration - never combine steroids w NSAIDS
  3. Delayed wound healing(not indicated for pre or post sx)
  4. Dec immune system func (never use if infection)
  5. sequesters lymphocytes and monocytes in bone marrow
  6. can cause abortion or premature parturition if larger dose in 2nd trimester K9, Bov, eq
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16
Q

What are some adverse effects of long term steroid use?

A
  1. GI ulceration - never combine w/ NSAIDs
  2. Inc risk of infection and cancer (suppression of Tcells/adaptive immunity)
  3. Muscle wasting
  4. Iatrogenic cushing’s dz
  5. iatrogenic diabetes mellitus 2nd to cushing’s in cats
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17
Q
A
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18
Q

What is the suppression of adrenal glands?

A

life threatening
risk of iatrogenic hypoadrenocorticism (addision’s dz)
occurs when glucocorticoid drugs have been used for longer than 5d then stopped abruptly
steroids suppress normal prod by adrenal gla (via suppression of neg feedback of HPA axis)
effect is reversible - step down steroid use to allow adrenal gland to get back to normal pros

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19
Q

How do we wean off steroids?

A

adrenal glands req time to return to normal func
for any tx longer than 5-7d, the patient MUSt be slowly weaned off the steroid to prevent acute addission crisis
Ex. schedule 2T BIDx7d;2T SIDx7d; 2T EODx7d, 1T EOD x7d
Always communicate to owner than abruptly stopping a steroid can cause severe side effects

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20
Q

What is prednisone and prednisolone indicated for. How many forms are there of them?

A
  1. chronic low dose (anti-inflam activity) for allergy, asthma, arthritis, iv injection for anaphylaxis
    2 forms of same drug
    Prednisone prodrug(inactive form)
    Prednisolone converted by liver enzyme to prednisolone (active form(
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21
Q

Why do we need to able to identify if an animal is on steroids

A

Cant be on NSAIDS because steroids have similar GI effects, so ulcers
Because we cant stop abruptly bc body’s natural steroid production is halted and need time to recover
Will interfere w/ lots of testing
lots of side effects
PU/PD/PP(owner should be informed)
GI upset -ulcers
immunosuppression
poor healing if going into sx

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22
Q

What are some tech notes about steroids?

A
  1. Fin out what current dose is if long-term use.
  2. Always inform owners of s/e
  3. Always inform owners of wean off
  4. Concurrent use of steroids/NSAIDS are contraindicated - allergic, older, arthritic **
  5. Low dose steroid therapy will not affect vx’s
  6. Name sound similar, be careful when selecting drug from pharmacy. Know IV vs suspension vs prenisone vs prenisolone
  7. Some req 1-4 mo until all physiological effects of drug are gone
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23
Q

What do NSAID’s provide? How do they work?

A

anti-inflam, and analgesia
work by blocking cyclooxygenase (COX) enzymes - stops prod of prostaglandins and thromboxane

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24
Q

What cells are involved in COX-1

A

Platelets: turns on platelets for clotting
Renal Cells: maintains blood flow to kidneys
Intensinal mucosal cells: turns on mucus prod (protects from acid, digestive juices)
Stomach cells: controls stomach acid prod

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25
Q

What are the cells and their functions of COX-2?

A

Inflam: promots inflam, fever, enhances pain signals
Fibrocytes: turns on tissue repair
GI cells: turns on healing of ulcers

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26
Q

What are the 2 classes of NSAIDS? What are they based upon?

A

Based on whether they inhib COX 1 and/or 2
1. Non-selective NSAIDS (1. older drugs, 2. Inhib COX 1+2, 3. dec inflam, fever, pain signal)
2. COX-2 electives
DIFFERENT ADVERSE REACTIONS

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27
Q

What are COX-2 selectives

A

newer drugs
inhib COX2, minimal to no COX1 inhibition
purpose: to decrease unwanted s/e (reduced risk of GI ulcers, renal effects, anti-platelet effects
Still some overlap and will also inhib COX1
may dec healing of pre-existng GI ulcers

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28
Q

What is the pharmacokinetics of NSAIDs

A

effectiveness and adverse effects (tolerance) varies w/ drug, species and individual patient (some drugs are more appropriate for certain species than others)
all are metabolized in liver, all are eliminated in kidneys (and slightly by biliary excretion), toxicity is increased if liver or kidney dz

29
Q

What are some veterinary NSAIDS for human OTC and equine/nonselective

A

HUMAN OTC
▫ Aspirin (acetylsalicylate acid, ASA)
▫ Ibuprofen (Motrin, Advil) ** AVOID**
EQUINE /NONSELECTIVE
▫ Phenylbutazone (aka “-bute”)
▫ Flunixin meglumine (Banamine®)
▫ Naproxen (Equiproxen®)
▫ Ketoprofentopical

30
Q

What are some veterinary NSAIDS for topical ophthalmic and SA/COX2 selective

A

TOPICAL OPTHALMIC
▫ Diclofenac (Voltaren®
SA/COX2 SELECTIVE
▫ Meloxicam (Metacam®)
▫ Carprofen (Rimadyl)
▫ Deracoxib (Deramaxx®)
▫ Firacoxib (Previcox®) – equine too
▫ Tolfenamic acid (Tolfedine®)
▫ Robenacoxib (Onsior®) – newest for cats

31
Q

What are the main indications for NSAIDs

A
  1. decrease inflam
  2. analgesia - one of most common used analgesic in vet med, for mild-mod pain, 2 mechanisms (1. dec inflam and 2. inhib prostaglandin synth bc they make pain receptors more sensitive), every good for pre-emp analgesia, works synergistically with opioids
  3. Reduce fever (anti-pyretic) diff mechanism than above
32
Q

What are the major adverse effects of NSAIDS?

A
  1. stomach and intestinal ulcers
  2. kidney damage
  3. prevents healing of GI ulcers
  4. Decrease clotting, risk of bleeding
  5. hepatotoxicity - rare
33
Q

What makes an animal more susceptible to NSAID adverse effects?

A

severity of s/e depends on which NSAID is prescribed and the patient
toxic effects inc w/ chronic use
Cats susceptible to ALL adverse effects - NSAID are metabolized by glucuronyl transferase
Cats do not prod much of this enzyme
drug accumulates > inc toxic risk
ex. Metacam: 0.05 mg/kg (cat), 0.1 mg/kg (dog)

34
Q

How can we minimize adverse effects?

A
  1. use PRN @ lowest effective dose
  2. never take more than 1 at a time
  3. avoid use in patients on steroids
  4. avoid use if kidney or liver dz
  5. caution in dehydrated, hypoproteinemic patient
  6. avoid concurrent use w/ nephrotoxic drugs
  7. avoid use in patients that are dehydrated or hypotensive
  8. avoid use in patients w/ existing Gi ulcers, patients undergo GI surgery
  9. Caution in cats
  10. Avoid in patients w/ bleeding disorders (aspirin
35
Q

What do we need if we’re going to use a human OTC drug for any animal species?

A

a prescription for ELDU

36
Q

What is NSAID toxicity?

A

Common - OD (too much/frequent), wrong patient, inappropriate admin of human OTC
V/D > bloody V/D, melena > kidney damage (vomit, PU/PD, anuria, acute resp dz) > neuro signs
EMERGENCY
IV fluids, diuresis, GI protectants, activate charcoal, liver protectants

37
Q

What is aspirin and what is it used for?

A

acetylsalicylic acid, COX non-selective - inhibs both COX1/2 enzymes. inhib of COX1 in platelets is irreversible
inexpensive, widely available as human OTC - ELDU in sm anim
primary use in vet med as an anticoagulant for mgnt of blood clots (cats)
there are better/safer drugs for tx’ inflam and pain
req glucuronyl transferase for inactivation

38
Q

What are the cautions of using aspirin in animals?

A

easy to OD cats - metabolize it slowly, t1/2 is 40h, compared to 71/2 in dogs
Not used for inflam control in Eq bc of short half-life and GI s/e
dec clotting; increased risk of bleeding - will inc risk of hemorrhage in patients undergoing sx - 21 days btw last dose and any sx (in dogs)
entric coated aspirin - not recommended

39
Q

What is important client communication with aspirin

A

Aspirin is NOT the same as other OTC human anti-inflams like ibuprofen, naproxen, acetaminophen
Clients should not replace the aspirin product w/ one of the above as it could prod severe s/e effects or death to their animal

40
Q

What is phenylbutazone?

A

AKA Bute, in EQ
tx’s musculoskeletal pain and laminitis
non-selective COX inhibitor, a highly protein bound drug
comes in oral paste/tablet/powder, injectable
in CAD, bute is not labeled for use in food-prod animals (including eq for slaughter to be used in food)Wha

41
Q

What are the adverse effects of bute?

A
  1. bone marrow suppression - resulting in neutropenia, thrombocytopenia, and anemia
    ANimals on long term usage should be monitored regularly via hematology lab testing
  2. TIssue necrosis - occurs if IV dosage form is accidentally injected IM or SQ
42
Q

What is flunixin meglumine?

A

banamine - non selective COX inhib
used for short-term tx of moderate pain and inflam in LA
oral/injectable (IV only avoid giving IM even though on label)
Bovine - shipping fever and coliform mastitis - IV only
Equine - Colic to alleviate visceral pain, musculoskeletal disorders
Guinea pigs - off label
**WDT’s

43
Q

What is the purpose of meloxicam use in cats?

A

inject: Limited to short-term use
Limited to 1 SQ injection post-op for sx pain - maker does not recommend a 2nd dose in cats
ORAL: After sx or acute, mild to mod musculoskeletal disorders in cats - peri-op use may be administered once daily (at 24hr intervals) for up to 2d, acute musculoskeletal disorders for up to four days
The safety of metacam has not been evaluated inbreeding, pregnant or lactating cats

44
Q

What is meloxicam?

A

COX 2 selective, highly protein bound, oral (liquid suspension, tablets) and injectable (has 30m onset of action), licensed versions for dog, cat, cattle
Used ELDU in exotic/zoo animals, including reptile and birds for tx of pain nd inflam

44
Q

What is the purpose of meloxicam use in dogs?

A

alleviation of inflam and pain in both acute and chronic musculo-skeletal disorders like osteoarthritis, pain associated w/ sx (SQ onset 30m) then oral (4hr onset)
Oral absorption almost complete in dogs when given with food
oral meloxicam solution contains xylitol
safe use of oral suspension in dogs <6mo, dogs for breeding, or in pregnant or lactating dogs not evaluated

45
Q

What is the purpose of using meloxicam in large animals?

A

for alleviation of pain and inflam
licensced for beef cattle, not lactating dairy cows
WDT 35 d from last treatment >slaughter

46
Q

What are the instructions when using melocixam(or any other NSAID)

A

Pr only, mus tbe hydrated, caution in older animals - liver and renal values often required, needs monitoring if chronic use
Show owners how to draw up oral dose - review dose size/volume w/ owners
give oral forms w/ food or 1 hour after - dec risk of V/D; Gi ulcer
do not give if not eating/drinking

47
Q

What is rimadyl?

A

generic: carprofen
COX2 selective
Carprofen has caused idiosyncratic acute hepatic toxicity in dogs (usually after 2-3wks from exposure)

48
Q

WHat is deramaxx?

A

Generic: deracoxib
COX2 selective
licensed versions for dofs but not cats
2 on label uses for osteoarthritic pain (chronic use)
post-sx pain (up to 7d)
Onset 1-2hr
oral form only
Gastric ulceration (more common than some other NSAIDs)

49
Q

What is previcox or equioxx?

A

COX2 selective
to control pain from osteoarthritic and orthopedic sx

50
Q

What is onisor?

A

Generic: robenacoxib
COX2 (no COX1 at therapeutic dose)
Newest NSAID: oral/injectable
labels for cats 1d/6days
also for dogs ($$$)
oral form w/ food
injectable has 3 d duration after single dose
same precautions and adverse effects as other NSAID’s

51
Q

What is the purpose of anafen/ketoprofen in cattle?

A

tx of fever, pain, inflam associated w/ variety of conditions including; resp tract, infections, mastitis, udder edema, downer cow syndrome, endotoxemia, simple gastrointestinal disorders, arthritis and traumatic musculoskeletal injuries

52
Q

What is the purpose of anafen/ketoprofen in swine

A

recommended for tx of fever and inflam associated w/ resp tract infections

53
Q

What is the purpose of anafen/ketoprofen in horses

A

Recommended for alleviated of inflam and pain associated w/ musculoskeletal disorders

54
Q

What is the purpose of anafen/ketoprofen in dogs and cats?

A

for alleviation of inflam, lameness and pain due to osteoarthritis, hip dysplasia, disc dz, spondylosis, panosteitis, trauma, and related musculoskeletal dz’s; for mgmt of post-surgical pain; for the symptomatic tx of fever

55
Q

Why should we avoid use of ibuprofen and naproxen?

A

COX non-selectives
Human OTC
often found in other medications
considered a toxin in vet med, avoid in vet species
no WDT for food animals
can cause acute fatal liver failure in cats/dogs
severe GI ulceration
adverse effects can occur with single dose

56
Q

Why should we avoid acetaminophen in vet med?

A

tylenol
not an NSAID
mechanism unknown but reduces the perception of pain
anti-pyretic, analgesic only - does NOT have anti-inflam activity
toxicity occurs @ very low dose in cats (high dose in dogs), single regular strength tablet can kill a cat - alters hemoglobin to methemeglobin (which does not carry O)
also hepatotoxic

57
Q

What is histamine?

A

Histamine released by cells and basophils
Release triggered by acute tissue damage, IgE binds to mast cells/basophils
Histamine binds to H1-receptors to turn on acute inflam pathway, causes vasodilation, edema, bronchoconstriction
Also binds to H2 receptors in GIT to turn on gastric acid prod

58
Q

What are antihistamines?

A

“stops” histamine
binds to histamine-receptor and blocks it from binding
does not have any influence on receptors that are already bound by histamine
Therefore, more effective at preventing than tx
“rebound effect” seen in humans not commonly noted in anims

59
Q

What are some clinical indications for anti-histamines? (h1 blockers)1

A
  1. preventing + tx’ing inflam due to allergy, atopy and asthma. It blocks inflam related to H1 receptor effects, also have anti-pruritic effect, also have anti-anxiety effect that calms patient who is otherwise painful and itchy
  2. Anaphylaxis - vx reactions, blocks inflame cascade and blocks vasodilation
  3. Bronchodilation - prevents smooth muscle contraction; used for COPD and asthma
60
Q

What are the s/e of antihistamines?

A

transient drowsiness, mild sedation
anticholinergic effecs like dry mouth, mydriasis, urine retention
At higher dose, V/D, nausea
Overdose can cause hyper excitability, disorientation, seizure and even death

61
Q

What is diphenhydramine?

A

benadryl
Indicated for emerg tx of anaphylaxis; including vx reactions. Can pre-treat patients at-risk for vx reactions. prevention/maintenance/tx of allergy, atopy and asthma
S/e are sedation and anticholinergic effects
ROutes: IV over 90s or can cause anaphylaxis
IM, SQ allow 15 min for effect
Oral for at home PRN and chronic maintenance

62
Q

What is the effect of vanectyl-P for antihistamine?

A

prenisolone + trimeprazine (antihistamine)
Commonly used in SA
Very effective for both acute and chronic prevention and tx of allergic dermatitis and atopy - anti-inflam, analgesic, prevents histamine activity, anti-anxiety, antipruritic
Presence of trimeprazine dec dose of steroid required
adverse effects mostly related to prednisolone

63
Q

What does vetoquinol contain? What IS vetoquinol?

A

antihistamine powder for horses
contains pyrilamine maleate (antihistamine + ephedrine hydrochloride (bronchodilator)

64
Q

What are immuno suppressants?

A

these drugs turn off the immune system
stops inflam and adaptive immunity
act by inhibiting lymphocytes (T cells and B cells)

65
Q

What are the clinical indications for immunosuppressants?

A

preventing rejection of grafts/transplants
control autoimmune dz (IMHA, mysathenia gravis, pemphigus, perianal fistula, atopy, immune-mediated polyarthritis, systemic lupus erythematosus)

66
Q

What are the adverse effects of immunosuppresants?

A

adverse effects vary depending on drug and patient
can range from V/D to acute liver failure and bone marrow suppression
ALL drugs cause immunosuppression - risk of infection and neoplasia, may interfere w/ ability to respond to vx’s

67
Q

What are some examples of immunosuppresants?

A

high dose steroids - inhib both T and B cells, high dose chronic use inc risk of GI ulcers, hepatopathy and iatrogenic Cushing’s dz
Cyclosporine
azothiaprine
oclacitinib (apoquel) for severe allergy in dogs

PHARMACOLOGY (12 decks)

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