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Pharmocology > Unit 4: antiinflammatories > Flashcards

Unit 4: antiinflammatories Flashcards

1
Q

Inflammation

A

Normal response to trauma, infection, neoplasia as first stage of tisseu repair
Part of the innate immune system
Non-specific
Will damage surrounding healthy tissues

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2
Q

Pain pathway

A

Transduction
Transmission
Modulation
Perception

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3
Q

Function of prostaglandins in inflammation

A

Produce the signs of inflammation by causing
Vasodilation (increased blood flow)
Smooth muscle contraction (edema, bronchoconstriction)
Heat, fever
Pain at site of injury
Protective action on the GIT wall, balance stomach pH through secretion of bicarbonate and increase mucus production
Function of thromboxane
Platelet activation→ clotting
Function of leukotrienes
Chemotaxis (attracts) WBCs
Activates WBCs
Increases vascular permeability (involved in vasodilation during anaphylaxis)
Bronchospasm

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4
Q

Mechanism of anti inflammatories

A

Turn down inflammation
By blocking the arachidonic acid pathway

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5
Q

Antiinflammatory classes

A

2 major classes to treat inflammation
Steroids
Non steroidal anti inflammatories (NSAIDs)
(antihistamines)

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6
Q

Steroids

A

Aka corticosteroids
Steroid drugs are called “exogenous steroids”
Act the same as “endogenous steroids” which are steroids naturally produced by the body
Endogenous steroids are produced by the adrenal glands
Both endogenous and exogenous steroids are part of the feedback loop in the hypothalamic-pituitary-adrenal axis (HPA axis)

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7
Q

NSAIDs block/indications/side effects and duration

A

Cycooxygenase
Decrease inflammation
Mild to moderate analgesia
Stops fever
Fewer
Shorter

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8
Q

Steroids block/indications/side effects and duration

A

Phospholipase + Cyclooxygenase
(to a lesser extent)
Decrease inflammation
Mild to moderate analgesia
Immunosuppression (blocks specific immunity) at high dose
More
Longer

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9
Q

Exogenous steroids

A

Aka steroid “drugs”
Can use as anti-inflammatory (similar to NSAIDs) at low dose
Decreases inflammation
Mild to moderate pain control
Does not control fever producing cytokines
At higher doses can be used to manage shock and have immunosuppressive effects
Longer acting than the NSAIDs; up to 4 months after single dose depending on which drug

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10
Q

Physiological effects of steroids

A

Involved in metabolites, electrolyte control, sex function
Glucocorticoids
Affect glucose, protein and fat metabolism
Inhibit inflammation, fibrocytes, platelets (low dose)
Suppresses lymphocytes (high dose)
Enhances/maximises fight or flight response
Decreases prostaglandin mediated sensation of pain
Mineralocorticoids
Controls water and electrolyte distribution
No influence on the immune system
Ex. aldosterone
Most exogenous steroids are glucocorticoids

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11
Q

How steroids stop inflammation

A

Inhibit phospholipase and (to a lesser extent) cyclooxygenase (COX)
Inhibit production of prostaglandins, thromboxane and leukotrienes

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12
Q

Most common clinical indications for steroids

A

Anti Inflammatory at low dose- e.g. eye, ear, arthritis (joint injections), asthma
Immune suppressant at high dose
Analgesic
Other
Appetite stimulant
Palliation of lymphosarcoma and mast cell tumors
Suppresses lymphocytes and inflammation
Treating proud flesh
Inhibits inflammation, platelets and fibrocytes
Addison’s disease (aka hypoadrenocorticism)
Replaces endogenous steroids

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13
Q

Adverse effects of local steroids

A

Topical formulas rarely cause systemic effects
Chronic use of eye drops can cause thinning of the cornea-**don’t use if cornea ulcered
Chronic use on skin can cause thinning of skin and decrease healing
Inhaled steroids can result in some systemic signs

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14
Q

Common systemic side effects of steroids that are less concerning

A

Almost always occur, not concerning
But warn owners
Polyphagia = increased appetite
PU/PD
Common; may cause owenres to complain about inappropriate urination
Panting
Common in dogs

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15
Q

Adverse effects of short term steroids

A

GI upset
Increased risk of given without food
Vomit diarrhoea, inappetence
May be precursor to GI ulcers
GI ulceration
Give with food to decrease risk
More likely with high dose or long term use
v/d, inappetence, melena, blood in v/d
Not as bas as NSAIDs if short term use
NEVER combine steroids with NSAIDS
Delayed wound healing
Due to inhibition of platelets, fibrocytes(and inflammation)
Not indicated for pre or post surgery
Decreases immune system function
Increases risk of infection; decreases ability to fight off infection
Never use if there is infection; will make infection worse
Sequesters lymphocytes and monocytes in bone marrow
Same as a stress leukogram
Can cause abortion or premature parturition if large dose in 2nd trimester K9, bovine, equine

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16
Q

Adverse effects of long term steroid use

A

GI ulceration
Very high risk with chronic use
Will supplement with GI protectants and antacids to prevent ulceration
NEVER combine steroids with NSAIDS
Increased risk of infection and cancer
Can occur with chronic low dose or high dose
Due to suppression of T cells/adaptive immunity
Increased risk of infection AND neoplasia
Iatrogenic cushing’s disease
Same as if adrenal gland was over producing steroids
Reversible; treat by weaning off corticosteroid; but any liver changes will be permanent
Iatrogenic diabetes mellitus secondary to cushings in cats

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17
Q

Suppression of adrenal gland with steroids

A

Life threatening
Risk of iatrogenic hypoadrenocorticism (addison’s disease)
Occurs when glucocorticoid drugs have been used for longer than 5 days then stopped abruptly
Steroids suppress normal production by adrenal gland
Via suppression of negative feedback of hypothalamus-pituitary-adrenal (HPA) axis
Effect is reversible
Step down steroid use to allow adrenal gland to get back to normal production

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18
Q

Prevention of suppression of the adrenal gland by steroids

A
  • weaning off steroids
    The adrenal glands require time to return to normal function
    For any treatment longer than 5-7 days, the patient MUST be slowly weaned off the steroid to prevent an acute Addisonian crisis
    Example of a weaning schedule
    2T BID x7d; 2T SID x 7d; 2T EOD x 7d; 1T EOD x7d
    Always communicate to an owner that abruptly stopping a steroid can cause severe side effects
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19
Q

Commonly used steroids are classified by

A

Classified by (1) duration of action, and (2) amount of glucocorticoid versus mineralocorticoid activity

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20
Q

How long does Hydrocortisone

A

<12 h Hydrocortisone – short-acting; topical only

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21
Q

How long does prednisone work

A

12-36 hours
cheap; oral/topical; less effective in cats/horse

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22
Q

How long does prednisolone work

A

12-36 h Prednisolone – active form of prednisone; oral/injectable/topical ($)

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23
Q

How long does triamcinolone work

A

12-36h Triamcinolone - oral/injectable; common in equine ($$)

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24
Q

How long does dexamethasone work

A

48h Dexamethasone - longer-acting; injectable/topical/oral; greater suppression of HPA-axis ($)

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25
Q

How long does methylpredisolone acetate work

A

~7 days Methylprednisolone acetate (DepoMedrol®)– long-acting
IM/SQ injectable; white suspension CANNOT give IV (30-40 day duration) ($)

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26
Q

How long does desoxycortisone privalate work

A

28d Desoxycortisone pivalate (Percorten®)– long acting injection for treating Addison’s ($$$$)

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27
Q

Prednisone/Prednisolone indicated for

A

Most commonly used. Indicated for
Chronic low dose (anti inflammatory activity) for allergy,a asthma arthritis
IV injection for anaphylaxis

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28
Q

Prednisone/Prednisolone are

A

Two forms of the same drug
Prednisone is a prodrug (inactive form)
Prednisone is converted by a liver enzyme to prednisolone (active form)
Cats and horses are not very efficient at this conversion, should be given prednisolone

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29
Q

Why you need to be able to identify steroids

A

Can’t be on NSAIDs
Can’t stop drug abruptly
Will interfere with lots of testing
Lots of side effects
PU/PD/PP (owner should be informed)
GI upset-ulcers
Immunosuppression
Poor healing if going into surgery

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30
Q

Tech notes about steroids

A

Always find out what the current dose is if long term use. Lots of PRN (as needed) use. Write in as part of history
Always inform owners of common, expected side effects (increased appetite, PUPD, panting)
Always inform owners of needing to wean off
Concurrent use of steroids and NSAIDs are contraindicated. Watch out for allergic patients and older, arthritic patients
Low dose steroid therapy will not affect vaccine efficacy
Names sound similar, so be careful when selecting the drug from the pharmacy. Know which ones are IV use, which are suspensions, prednisone versus prednisolone
Depending on the steroid, requires 1-4 months from time meds are stopped until all physiological effects of drugs are gone

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31
Q

NSAIDs are

A

Anti Inflammatory and analgesia
Work by blocking cyclooxygenase (COX) enzymes
Stop production of prostaglandins and thromboxane

32
Q

Function of COX-1

A

Turns on platelets for clotting
Maintain blood flow to kidneys
Turns on mucus production
(protect from acid, digestive juices)
Controls stomach acid production

33
Q

Function of COX-2

A

Promotes inflammation
Promotes fever
Enhances pain signals
Turn on tissue repair
Turns on whaling of ulcers

34
Q

2 classes of NSAIDs

A

NSAIDS are separated into 2 classes based on whether they inhibit: COX-1 and/or COX-2
Nonselective NSAIDs
Older drugs
Inhibit COX-1 and COX-2
Decreases inflammation, fever and pain signalling
COX-2 selectives
Different adverse effects

35
Q

COX-2 selectives

A

Newer drugs
Inhibit COX-2; minimal to no COX-1 inhibition
Purpose: to decrease unwanted side effects
Reduced risk of GI ulcers, renal effects, antiplatelets effects
Still some overlap wand will also inhibit COX-1
May decrease whaling of pre-existing GI ulcers

36
Q

NSAIDs pharmacokinetics

A

Effectiveness and adverse effects (i.e., tolerance) varies with drug, species and individual patient
Some drugs are more appropriate for certain species than others
All are metabolized in the liver
All are eliminated in the kidneys (and slightly by biliary excretion)
Toxicity is increased if liver or kidney disease

37
Q

Veterinary NSAIDs

A

Human OTC
Aspirin (acetylsalicylate acid, ASA) AVOID
Equine /nonselective
Ibuprofen (Motrin, Advil)
Phenylbutazone (aka “-bute”)
Flunixin meglumine (Banamine®)
Naproxen (Equiproxen®)
Ketoprofen
Topical ophthalmic
Diclofenac (Voltaren®
SA/COX-2 selective
Meloxicam (Metacam®)
Carprofen (Rimadyl)
Deracoxib (Deramaxx®)
Firacoxib (Previcox®) –equine too
Tolfenamic acid (Tolfedine®)
Robenacoxib (Onsior®)– newest for cats

38
Q

Main indications for NSAIDs

A

Decrease inflammation
Analgesia
One of most commonly used analgesics in vet med
Mild to moderate pain
2 mechanisms: (1) decreasing inflammation and (2) inhibiting prostaglandin synthesis (prostaglandins make pain receptors more sensitive)
Very good for pre-emptive analgesia
Works synergistically with opioids
Reduce fever (anti-pyretic)
Different mechanism than the above

39
Q

Major Adverse Effects of NSAIDs

A

Stomach and intestinal ulcers
Kidney damage
Prevents healing of GI ulcers
Decreases clotting, risk of bleeding
Hepatotoxicity - rare

40
Q

Susceptibility to NSAID Adverse Effects

A

Severity of side-effects depends on which NSAID is prescribed and the patient
Toxic effects increase with chronic use
Cats susceptible to ALL adverse effects
NSAIDs are metabolized by glucuronyl transferase
Cats do not produce much of this enzyme
Drug accumulates → increases toxic risk
Ex. Metacam dose: 0.05 mg/kg (cat), 0.1 mg/kg (dog)

41
Q

Minimizing Adverse Effects of NSAIDs

A

Use PRN (as needed) at lowest effective dose
Never take more than one NSAID at a time
Allow wash out period between NSAIDs
Avoid use in patients on steroids
Avoid use if kidney or liver disease
Caution in dehydrated, hypoproteinemic patients
Avoid concurrent use with nephrotoxic drugs
Avoid use in patients that are dehydrated or hypotensive
Avoid use in patients with existing GI ulcers, patients undergoing GI surgery
Caution in cats
Avoid in patients with bleeding disorders
Especially aspirin
Remember: Human OTC drugs require a prescription for ELDU use in any animal species.

42
Q

NSAID TOXICITY

A

Common
Overdose (too much, too frequent)
Wrong patient
Inappropriate administration of human OTC products
Vomit/diarrhea →bloody v/d, melena→kidney damage (vomit, PU/PD, anuria, Acute Respiratory Disease) → neurological signs
Emergency
IV fluids, diuresis, GI protectants, activate charcoal, liver protectants

43
Q

Aspirin (acetylsalicylic acid) works by

A

COX non-selective
Inhibits BOTH COX-1 and COX-2 enzymes
Inhibition of COX-1 in platelets is irreversible
Inexpensive, widely available as human OTC
ELDU in small animal
Primary use in vet med as an anticoagulant for management of blood clots (cats)
There are better/safer drugs for treating inflammation and pain
Requires glucuronyl transferase for inactivation

44
Q

Cautions when using aspirin

A

Easy to overdose in cats
Cats metabolize very slowly
t½ is 40 h in cats compared t0 7 ½ h in dogs
Not used for inflammation control in Equine
Due to short half life and GI side effects
Decreases clotting; increased risk of bleeding
Will increase risk of hemorrhage in patients undergoing surgery
21-days between last dose and any surgery (in dogs)
Entric coated Aspirin – not recommended

45
Q

Client communication with aspirin

A

Important explain that aspirin is not the same as other OTC human anti-inflammatories such as :
Ibuprofen (Advil® ,Motrin®)
Naproxen (Aleve®)
Acetaminphen (Tylenol®)
Clients should not replace the aspirin product with one of the above as it could produce severe side effects or death to their animal

46
Q

Phenylbutazone (“BUTE”)

A

Equine: treating musculoskeletal pain and laminitis
Non-selective COX inhibitor
A highly protein bound drug
Many versions available
Oral paste/tablet/powder; injectable
In Canada Phenylbutazone is not labeled for use in food-producing animals
including horses that are to be slaughtered for use in food.

47
Q

Adverse Effects of bute

A

Bone marrow suppression
Resulting in neutropenia, thrombocytopenia and anemia
Animals on Long term usage should be monitored regularly via hematology lab testing
Tissue necrosis
Occurs if IV dosage form is accidentally injected IM or SQ

48
Q

Flunixin meglumine - Banamine®

A

Non-selective COX inhibitor
Used for short-term treatment of moderate pain and inflammation in Large Animals
Oral and injectable (IV only avoid giving IM even though is on label)
Bovine
Shipping fever and coliform mastitis - IV ONLY
Equine
COLIC - alleviates visceral pain
musculoskeletal disorders
Guinea pigs – off label
**WDTs

49
Q

Meloxicam works against

A

Cox 2 Selective
highly protein bound
Oral (liquid suspension, tablets) and Injectable (has 30 min onset of action)
Licensed versions for Dog, Cat, Cattle
Used extra label in many exotic and zoo animals, including reptiles and birds, for treatment of pain and inflammation.

50
Q

Meloxicam use in SA (dogs)

A

alleviation of inflammation and pain in both acute and chronic musculo-skeletal disorders
Osteoarthritis
Pain associated with surgery
SQ (onset 30 min), then switch to oral (4 h onset)
Oral absorption is almost complete in dogs when administered with food.
The oral meloxicam solution of meloxicam contains xylitol
Safe use of Oral Suspension in dogs younger than 6 months of age, dogs used for breeding, or in pregnant or lactating dogs has not been evaluated

51
Q

Meloxicam use in cats (oral)

A

following surgery or associated with acute, mild to moderate musculoskeletal disorders in cats.
Peri-operative use may be administered once daily (at 24-hour intervals) for up to two days
Acute musculoskeletal disorders for up to four days
The safety of Metacam has not been evaluated in breeding, pregnant or lactating cats.

52
Q

Meloxicam use in cats (injectable)

A

Use in cats is limited to short-term use
Limited to single SQ injection post-operative for surgical pain
The manufacturer (metacam®) does not recommend a second dose of meloxicam injection to cats.

53
Q

Meloxicam in LA

A

Injectable and Oral solution available
For alleviation of pain and inflammation
Licensed for beef cattle not lactating dairy cows
WDT
35 days from last treatment– slaughter

54
Q

Instructions when using meloxicam (or any other NSAID)

A

Prescription only
Must be 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 with owners
Give oral forms with food or 1 hour after
Decreases risk of vomit/diarrhea; GI ulcer
Do not give if not eating/drinking

55
Q

Rimadyl /carprofen(zoetis)

A

Generic: carprofen
COX-2 Selective
In rare cases, carprofen has caused idiosyncratic acute hepatic toxicity in dogs.
Signs of toxicity usually appear 2-3 weeks after exposure

56
Q

DERAMAXX® (deracoxib)

A

Generic: deracoxib
COX-2 selective
Licensed versions for Dog (25, 75, 100 mg tabs), not cats
2 on-label uses:
Osteoarthritic pain (chronic use)
Post-surgical pain (up to 7d)
Onset: 1-2 hour
Oral form only
Gastric ulceration (may be more common than some other NSAIDs)

57
Q

PREVICOX®- canine
Equioxx®-horses
work against

A

(firocoxib)
COX-2 selective
To control pain from osteoarthritis and orthopedic surgery

58
Q

ONSIOR® (robenacoxib) works for and what forms exist

A

Generic: robenacoxib
COX-2 (no COX-1 at therapeutic dose)
Newest NSAID: oral tabs and injectable
Labelled for cats once a day up to 6 days
Also available for dogs ($$$)
Oral form must be given with food
Injectable form has 3 days duration after single dose
Same precautions and adverse effects as other NSAIDs
May have slight less systemic effects as drug concentrates in inflamed tissues

59
Q

ANAFEN® - Ketoprofen use in cattle

A

Cattle: treatment of fever, pain and inflammation associated with a variety of conditions including: respiratory tract infections, mastitis, udder edema, downer cow syndrome, endotoxemia, simple gastrointestinal disorders, arthritis and traumatic musculoskeletal injuries.

60
Q

ANAFEN® - Ketoprofen use in swine

A

Swine: recommended for the treatment of fever and inflammation associated with respiratory tract infections.

61
Q

ANAFEN® - Ketoprofen use in dogs and cats

A

Dogs and Cats: for the alleviation of inflammation, lameness and pain due to osteoarthritis, hip dysplasia, disc disease, spondylosis, panosteitis, trauma, and related musculoskeletal diseases; for the management of post- surgical pain; for the symptomatic treatment of fever.

62
Q

ANAFEN® - Ketoprofen use in horses

A

Horses: recommended for the alleviation of inflammation and pain associated with musculoskeletal disorders.

63
Q

Human OTC Products to AVOID and why

A

(Advil®, Motrin®) - Ibuprofen,(Aleve®) - Naproxen
COX non-selectives
Human OTC
Often found in other medications (i.e., cough meds and muscle relaxants)
Considered a toxin in vet med
AVOID in vet species
No WDT for food animals
Can cause acute fatal liver failure in dogs, cats
Severe GI ulceration
Adverse effects can occur with single dose
Acetaminophen
Tylenol®
Not an NSAID
Mechanism unknown but reduces the perception of pain;
Anti-pyretic, analgesic only
Does NOT have anti-inflammatory activity
Toxicity occurs at very low dose in cats (high dose in dogs). Single regular strength tablet can kill a cat
Alters hemoglobin to methemoglobin (which does not carry oxygen)
Also hepatotoxic

64
Q

Histamine

A

Histamine is released by mast cells and basophils; to lesser degree by platelets
Release is triggered by:
Acute tissue damage
IgE binding to mast cells and basophils
Histamine binds to H1-receptors
Turns on acute inflammation pathway
Causes vasodilation and edema
Causes bronchoconstriction
Histamine also binds to H2-receptors in GIT
Turns on gastric acid production – will cover in GI section

65
Q

Antihistamines

A

Anti-histamine = “stops” histamine
Binds to histamine-receptor and blocks histamine from binding
Do not have any influence on receptors that are already bound by histamine
Therefore, more effective at prevention than treatment of a histamine response
“Rebound effect” seen in humans not commonly noted in animals

66
Q

Clinical indications of antihistamines

A

Major indications for antihistamines (H1 blockers):
Preventing and treating inflammation due to allergy, atopy and asthma
Blocks inflammation related to H1 receptor effects.
Also has anti-pruritic effect
Also has anti-anxiety effect that calms patient who is otherwise painful and itchy
Anaphylaxis
vaccine reactions
Blocks inflammation cascade and blocks vasodilation
Bronchodilation
Prevents

67
Q

Side effects of antihistamines

A

Few minor side effects at therapeutic dose
Transient drowsiness, mild sedation most common
Anticholinergic effects such as dry mouth, mydriasis, urine retention
At higher dose, can cause
Vomit, diarrhea, nausea
Overdose can cause hyper excitability, disorientation, seizures and even death

68
Q

Diphenhydramine (Benadryl®) indications

A

Trade name and generics available; names used interchangeably. Must know both!
Main indications:
#1 drug or emergency treatment of anaphylaxis; including vaccine reactions (in emergency drug kit)
Can pre-treat patients at-risk for vaccine reactions
Prevention/maintenance/treatment of allergy, atopy and asthma

69
Q

Diphenhydramine (Benadryl®) side effects and routes

A

Side effects are sedation and anticholinergic effects
Routes:
IV is over 90 sec or can cause anaphylaxis
IM, SQ – allow 15 min for effect
Oral for at home PRN and chronic maintenance

70
Q

Vanectyl-P® used for and in

A

Prednisolone + trimeprazine (antihistamine)
Commonly used in SA
Very effective for both acute and chronic prevention and treatment of allergic dermatitis and atopy
Anti-inflammatory, analgesic, prevents histamine activity, anti-anxiety, antipruritic
Presence of trimeprazine decreases dose of steroid required

71
Q

Vanectyl-P® adverse effects

A

Adverse effects are mostly related to the prednisolone
List 6 side effects of short or long term usage

72
Q

Antihistamine Powder® Vetoquinol used in and contains

A

Horses
Contains:
pyrilamine maleate (antihistamine)
+ ephedrine hydrochloride (bronchodilator)

73
Q

Immunosuppressants

A

These drugs TURN OFF the immune system
Stop inflammation AND adaptive immunity
Act by inhibiting lymphoyctes (T cells and B cells)

74
Q

Clinical indications of immunosupressants

A

Preventing rejection of grafts/transplants
Control autoimmune diseases (immune-mediate hemolytic anemia (IMHA), myasthenia gravis, pemphigus, perianal fistula, atopy, immune-mediated polyarthritis, systemic lupus erythematosus)

75
Q

Adverse effects of immunosuppressants

A

Adverse effects vary depending on the drug and patient
Can range from vomit and diarrhea to acute liver failure and bone marrow suppression
ALL drugs cause immunosuppression
Increased risk of infection
Increased risk of neoplasia
May interfere with ability to respond to vaccines

76
Q

Examples of Immunosuppressants

A

High dose steroids
At high dose, inhibit both T cells and B cells
See notes on glucocorticoids for adverse side effects. High dose chronic use increases risk of GI ulcerations, hepatopathy and iatrogenic Cushing’s disease
cyclosporine (Atopica®)
azothiaprine (Imuran®)
oclacitinib (Apoquel®) – for severe allergy in dogs

Pharmocology (10 decks)

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