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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
What are the cells and their functions of COX-2?
Inflam: promots inflam, fever, enhances pain signals Fibrocytes: turns on tissue repair GI cells: turns on healing of ulcers
26
What are the 2 classes of NSAIDS? What are they based upon?
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
27
What are COX-2 selectives
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
28
What is the pharmacokinetics of NSAIDs
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
What are some veterinary NSAIDS for human OTC and equine/nonselective
HUMAN OTC ▫ Aspirin (acetylsalicylate acid, ASA) ▫ Ibuprofen (Motrin, Advil) ** AVOID** EQUINE /NONSELECTIVE ▫ Phenylbutazone (aka “-bute”) ▫ Flunixin meglumine (Banamine®) ▫ Naproxen (Equiproxen®) ▫ Ketoprofentopical
30
What are some veterinary NSAIDS for topical ophthalmic and SA/COX2 selective
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
What are the main indications for NSAIDs
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
What are the major adverse effects of NSAIDS?
1. stomach and intestinal ulcers 2. kidney damage 3. prevents healing of GI ulcers 4. Decrease clotting, risk of bleeding 5. hepatotoxicity - rare
33
What makes an animal more susceptible to NSAID adverse effects?
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
How can we minimize adverse effects?
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 6. avoid use in patients that are dehydrated or hypotensive 7. avoid use in patients w/ existing Gi ulcers, patients undergo GI surgery 8. Caution in cats 9. Avoid in patients w/ bleeding disorders (aspirin
35
What do we need if we're going to use a human OTC drug for any animal species?
a prescription for ELDU
36
What is NSAID toxicity?
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
What is aspirin and what is it used for?
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
What are the cautions of using aspirin in animals?
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
What is important client communication with aspirin
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
What is phenylbutazone?
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
What are the adverse effects of bute?
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
What is flunixin meglumine?
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
What is the purpose of meloxicam use in cats?
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
What is meloxicam?
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
What is the purpose of meloxicam use in dogs?
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
What is the purpose of using meloxicam in large animals?
for alleviation of pain and inflam licensced for beef cattle, not lactating dairy cows WDT 35 d from last treatment >slaughter
46
What are the instructions when using melocixam(or any other NSAID)
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
What is rimadyl?
generic: carprofen COX2 selective Carprofen has caused idiosyncratic acute hepatic toxicity in dogs (usually after 2-3wks from exposure)
48
WHat is deramaxx?
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
What is previcox or equioxx?
COX2 selective to control pain from osteoarthritic and orthopedic sx
50
What is onisor?
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
What is the purpose of anafen/ketoprofen in cattle?
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
What is the purpose of anafen/ketoprofen in swine
recommended for tx of fever and inflam associated w/ resp tract infections
53
What is the purpose of anafen/ketoprofen in horses
Recommended for alleviated of inflam and pain associated w/ musculoskeletal disorders
54
What is the purpose of anafen/ketoprofen in dogs and cats?
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
Why should we avoid use of ibuprofen and naproxen?
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
Why should we avoid acetaminophen in vet med?
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
What is histamine?
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
What are antihistamines?
"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
What are some clinical indications for anti-histamines? (h1 blockers)1
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
What are the s/e of antihistamines?
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
What is diphenhydramine?
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
What is the effect of vanectyl-P for antihistamine?
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
What does vetoquinol contain? What IS vetoquinol?
antihistamine powder for horses contains pyrilamine maleate (antihistamine + ephedrine hydrochloride (bronchodilator)
64
What are immuno suppressants?
these drugs turn off the immune system stops inflam and adaptive immunity act by inhibiting lymphocytes (T cells and B cells)
65
What are the clinical indications for immunosuppressants?
preventing rejection of grafts/transplants control autoimmune dz (IMHA, mysathenia gravis, pemphigus, perianal fistula, atopy, immune-mediated polyarthritis, systemic lupus erythematosus)
66
What are the adverse effects of immunosuppresants?
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
What are some examples of immunosuppresants?
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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