Unit 2: Atopy Pharmacology Flashcards
1
Q
Atopy is AKA as _____ _____.
A
atopic dermatitis
2
Q
What is atopy?
A
Genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE, most commonly directed against environmental allergens.
3
Q
Up to ___% of the population has atopy.
A
10
4
Q
What is the age of onset of atopy?
A
6 months to 3 years
5
Q
What are the breed dispositions for atopy?
A
Frenchies, terriers, retrievers, bulldogs, GSD
(but any dog at any age can develop it)
6
Q
What are common clinical signs of atopy?
A
Pruritus, otitis externa, hot spots, acral lick dermatitis, hives (rare), recurring skin infections, alopecia, +/- lichenification
7
Q
T/F: There is no definitive test for atopy.
A
True
8
Q
Do allergy tests diagnose or confirm atopy?
A
No
9
Q
What are Favrot’s Criteria?
(There are 8 of them)
A
- Age of onset <3 yo
- Dog kept mostly indoors
- Pruritus is steroid responsive
- Pruritus was first symptom
- Affected front paws
- Affected ear pinnae
- Non-affected ear margins
- Non-affected dorsolumbar region
10
Q
How many of Favrot’s criteria does a dog usually have to assume it is mostl likely atopy?
A
5
11
Q
What type of diagnosis is atopy?
A
diagnosis of exclusion
12
Q
What are the 4 major causes of allergy?
A
Fleas, parasite hypersensitivity, cutaneous adverse food reaction, canine atopy
13
Q
What is the #1 reason for dogs to be itchy?
A
Fleas (C. felis)
14
Q
What parasites are likely to causes hypersensitivity?
A
Scabies and Cheyletiella
15
Q
What is the BASIC mechanism for allergy?
A
Allergen enters the system –> allergen binds IgE –> IgE binds mast cells –> allergic response
16
Q
What are the predominant cell types in atopy?
A
lymphocytes and langerhans cells
17
Q
What type of lymphocytes are involved in atopy?
A
Th1, Th2, Treg
18
Q
What are some other cell types involved in atopy?
A
Mast cells, eosinophils, neutrophils, keratinocytes
19
Q
What composes the barrier function of the skin?
A
Lipid lamellae surrounded by keratinocytes - composed of ceramides, 3 FAs, and cholesterol
20
Q
What does the barrier function of atopic patients look like?
A
There are holes in the lipid lamellae
21
Q
What are the components of the swiss cheese atopy comparison?
A
- Keratinocytes are active in the immune
- Ceramides are deficient
- Filaggrin is mutated
- Increased water loss
22
Q
What cytokine stimulates itch?
A
IL-31
23
Q
What is the most important aspect of management?
A
Client education
24
Q
What supportive care can we give atopic patients?
A
antihistamines, FFAs, bathing and barrier care
25
What disease-specific therapies can we give to atopic patients?
GCs, cyclosporine, IL-31 inhibitors, allergen-specific immunotherapy
26
What are the most common antihistamines given to atopic patients?
Diphenhydramine and Cetirizine (Zyrtec)
27
What antihistamine is Rx?
Hydroxyzine
28
What antihistamine is the most expensive?
Fexofenadine (Allegra)
29
Antihistamines do not stop \_\_\_\_\_.
pruritus
30
Why are antihistamines used?
1. Prevention of subsequent flare-ups and safety
2. Helpful in mild cases
3. Drug-sparing effects
31
What fatty acids can be used?
Omega-6 and Omega-3
32
What is the MOA of FAs?
Downregulate inflammatory eicosanoid production, inhibit inflammatory cell activation, and improve epidermal lipid quality
33
What are some examples of commercial diets that contain FAs?
Hill's Derm Defense, Purina DRM, RC Skin Support
34
What are the purposes of bathing?
Remove allergen, soothe and hydrate, deliver meds, barrier care (ceramides and precursors)
35
What are things to consider for bathing?
Can and will the owners do it?
Contact time, water temperature, drying
36
What is the downside to GC therapy?
Many adverse effects
37
GCs are made for ____ use in atopy.
Short-term
38
What 2 side effects should owners always be warned about with GCs?
PU/PD, polyphagia
39
What are additional side effects of GCs?
Behavior changes, panting, fat redistribution, muscle wasting, recurrent UTIs, hepatopathy
40
What are clinical syndromes/diseases that can occur as a result of GC therapy?
Iatrogenic Cushing's, DM, thyroid suppression, pancreatitis, calcinosis cutis, weakened ligaments
41
What are 6 reasons when you should consider GCs?
1. Acute flares and first time episodes
2. Prior to starting IL-31 inhibitors
3. Seasonal disease (3 mos or less)
4. Other forms of therapy have failed
5. Multimodal therapy
6. Financial constraints
42
What are the 2 phases of GC therapy?
Reactive and Proactive
43
What does reactive therapy (phase 1) mean?
Induction of remission
44
What drugs would you use at point A?
Oral +/- topical GCs
45
What drugs would you use at point B?
Oclacitinib
46
What therapies would you use at A?
Allergen avoidance +/- immunotherapy
47
What drug would you use at B?
lokivetmab
48
What drug would you use at C?
cyclosporine
49
What drug would you use at D?
Oral +/- topical GCs
50
What drugs would you use at E?
Proactive topical GCs, Oclacitinib
51
What formulation of GC should be used in atopy?
Oral only
52
T/F: GCs should never be combined with other things
False; should be adjunctive with baths, fish oils, diet, etc.
53
What is the anti-inflammatory dose of steroids?
0.5-1 mg/kg/day PO (prednisone)
54
What is the minimum age and weight for cyclosporine use?
6 months, 4#
55
What is the basic MOA of cyclosporine?
It messes with IL-2 production from lymphocytes
56
What type of drug is cyclosporine?
Calcineurin inhibitor
57
What happens when IL-2 transcription is blocked?
Lymphocyte proliferation is suppressed and further production of relevant cytokines is inhibited
58
What are the 3 functions of a calcineurin inhibitor?
1. Blocks IL-2 transcription
2. Decreases APC #s and activation
3. Decreases mast cell and eosinophil activation and production
59
What is the time to effect and overall efficacy of cyclosporine?
6 weeks and works in 4/5 dogs
60
What are possible reasons for failure of cyclosporine?
Dog doesn't tolerate it, cost/benefit ratio to woner, dog has food allergy that we missed, dog has secondary infections that haven't been properly addressed
61
How often should monitoring be done with cyclosporine?
every 6 months to 1 year
62
What are common adverse events of cyclosporine?
V/D, anorexia, gingival hyperplasia, hypertrichosis
63
What are 6 reasons to consider CsA?
1. Patient \>6 mos of age
2. Smaller dogs (more cost effective)
3. Condition is more inflammatory
4. Otitis is major manifestation
5. IL-31 inhibitors are ineffective or contraindicated
6. Allergen specific immunotherapy has failed
64
What are the 2 IL-31 inhibitors?
Apoquel and Cytopoint
65
How many patients benefit from Apoquel?
60-70%
66
What is the FDA labeled use for Apoquel?
Control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 mos of age
67
What is the MOA of Apoquel?
JAK inhibitor (1 and 3), suppresses IL-31 signaling, and suppresses other CKs involved with the cellular and inflammatory response ot atopy
68
What other CKs does Apoquel suppress?
IL-2, 4, 6, 13
69
What is the overall success of Apoquel?
Works in 6/10 dogs BID - but long term labeled use is SID and no longer works in 4/10 patients
70
What is the #1 adverse event with Apoquel?
V/D and anorexia
71
What are 3 things which Apoquel might increase susceptibility to?
Bacterial infections, viral papillomas, demodicosis
72
What are additional side effects of Apoquel?
Lethargy and behavior change, increased thirst, weight loss or gain
73
What are 5 reasons when you should consider Apoquel?
1. Patient is \>1 yo
2. Pruritus is main symptom or presentation
3. Owners do not wish to pursue ASIT
4. Recurrent pyoderma or *Malassezia* dermatitis
5. Owner elects this form of therapy given options
74
Who is cytopoint labeled under? What is the label?
USDA - Shown to be effective for the treatment of dogs against allergic dermatitis and atopic dermatitis
75
What does it mean if a drug is USDA-labeled?
It is safe but doesn't have to show efficacy
76
What type of drug is Cytopoint?
Lokivetmab (monoclonal Ab)
77
Why can't cytopoint be used in cats?
It is a mAb which is produced for and is identical to the spp that the drug is intended for (dogs)
78
What are the 4 unique aspects of mABs?
1. Administered by injection
2. Long half-lives
3. Very targeted therapy with anrrower adverse event profiles
4. Metabolized and excreted differently
79
How does cytopoint work?
1. Ab binds and prevents binding of a protein to its receptor
2. Ab has an agonist/antagonist effect on a membrane R
3. Ab eliminates virus or malignant cell by C' or cytotoxicity
80
What is nice about Cytopoint vs the other therapies (steroids, CsA, Apoquel)?
It has the least adverse effects
81
What is the duration of activity of Cytopoint?
4-8 weeks (usually 4)
82
What is the onset of action of Cytopoint?
\<72 hr
83
What is the efficacy of Cytopoint?
7/10 dogs
84
What are the possible adverse effects of Cytopoint?
GI upset, lethargy, injection site discomfort
85
What are the major advantages to using Cytopoint?
Any age, any concurrent disease, any concurrent meds
86
When should Cytopoint be considered?
In any patient with atopy whose major symptom is pruritus, and in multimodal therapy
87
What does ASIT stand for?
allergen specific immunotherapy
88
ASIT is the most _____ long term management strategy.
economical
89
ASIT lacks long-term \_\_\_\_\_.
complications
90
ASIT is the best chance for a \_\_\_\_\_.
"cure"
91
What are the 5 indications for ASIT?
1. Any atopic patient (early/first choice)
2. Symptomatic therapy is not effective *alone*
3. Patient can't tolerate medical options
4. Patient has conflicting concurrent medical conditions (chronic infections, DM)
5. Owner chooses to address cause vs. symptoms
92
What are the multimodal components of the MOA of ASIT?
T cells, Ig class switching, CK expression
93
What is allergen selection for ASIT based on?
history and test results
94
The _____ of the reaction in ASIT does not necessarily correlate with the _____ of the allergen.
strength, significance
95
What are the 5 ASIT protocols?
Classic, Modified, Rush, Sublingual (SLIT), Intralymphatic
96
What is the classic ASIT protocol?
2 or 3 vial
Start out with 200-1000 PNU vial and progress to 10,000-20,000 PNU maintenance vial
Frequent injections
97
What is the modified ASIT protocol?
Starts with 20,000 PNU vial
98
What is the rush ASIT protocol?
Series of injections reaching maintenance in a day
99
What is the sublingual ASIT protocol?
3 vial series with increasing []
Given twice a day
100
When might we see improvement with the intralymphatic ASIT protocol?
By the 3rd injection
101
What is the main side effect of ASIT no matter what the route is?
Increased pruritus at the site of administration
102
What are other side effects of ASIT?
Swelling at injection site, urticaria/angiodema, anaphylaxis, V/D
103
What is the efficacy of ASIT?
60-70% of dogs demonstrate improvement
104
How long does it take for ASIT benefits to show?
6-12 months
105
What is RESPIT?
Regionally-specific immunotherapy available as an injectable or oral spray
