Unit 2: Atopy Pharmacology Flashcards
Atopy is AKA as _____ _____.
atopic dermatitis
What is atopy?
Genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE, most commonly directed against environmental allergens.
Up to ___% of the population has atopy.
10
What is the age of onset of atopy?
6 months to 3 years
What are the breed dispositions for atopy?
Frenchies, terriers, retrievers, bulldogs, GSD
(but any dog at any age can develop it)
What are common clinical signs of atopy?
Pruritus, otitis externa, hot spots, acral lick dermatitis, hives (rare), recurring skin infections, alopecia, +/- lichenification
T/F: There is no definitive test for atopy.
True
Do allergy tests diagnose or confirm atopy?
No
What are Favrot’s Criteria?
(There are 8 of them)
- 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
How many of Favrot’s criteria does a dog usually have to assume it is mostl likely atopy?
5
What type of diagnosis is atopy?
diagnosis of exclusion
What are the 4 major causes of allergy?
Fleas, parasite hypersensitivity, cutaneous adverse food reaction, canine atopy
What is the #1 reason for dogs to be itchy?
Fleas (C. felis)
What parasites are likely to causes hypersensitivity?
Scabies and Cheyletiella
What is the BASIC mechanism for allergy?
Allergen enters the system –> allergen binds IgE –> IgE binds mast cells –> allergic response
What are the predominant cell types in atopy?
lymphocytes and langerhans cells
What type of lymphocytes are involved in atopy?
Th1, Th2, Treg
What are some other cell types involved in atopy?
Mast cells, eosinophils, neutrophils, keratinocytes
What composes the barrier function of the skin?
Lipid lamellae surrounded by keratinocytes - composed of ceramides, 3 FAs, and cholesterol
What does the barrier function of atopic patients look like?
There are holes in the lipid lamellae
What are the components of the swiss cheese atopy comparison?
- Keratinocytes are active in the immune
- Ceramides are deficient
- Filaggrin is mutated
- Increased water loss
What cytokine stimulates itch?
IL-31
What is the most important aspect of management?
Client education
What supportive care can we give atopic patients?
antihistamines, FFAs, bathing and barrier care
What disease-specific therapies can we give to atopic patients?
GCs, cyclosporine, IL-31 inhibitors, allergen-specific immunotherapy
What are the most common antihistamines given to atopic patients?
Diphenhydramine and Cetirizine (Zyrtec)
What antihistamine is Rx?
Hydroxyzine
What antihistamine is the most expensive?
Fexofenadine (Allegra)
Antihistamines do not stop _____.
pruritus
Why are antihistamines used?
- Prevention of subsequent flare-ups and safety
- Helpful in mild cases
- Drug-sparing effects
What fatty acids can be used?
Omega-6 and Omega-3
What is the MOA of FAs?
Downregulate inflammatory eicosanoid production, inhibit inflammatory cell activation, and improve epidermal lipid quality
What are some examples of commercial diets that contain FAs?
Hill’s Derm Defense, Purina DRM, RC Skin Support
What are the purposes of bathing?
Remove allergen, soothe and hydrate, deliver meds, barrier care (ceramides and precursors)
What are things to consider for bathing?
Can and will the owners do it?
Contact time, water temperature, drying
What is the downside to GC therapy?
Many adverse effects
GCs are made for ____ use in atopy.
Short-term
What 2 side effects should owners always be warned about with GCs?
PU/PD, polyphagia
What are additional side effects of GCs?
Behavior changes, panting, fat redistribution, muscle wasting, recurrent UTIs, hepatopathy
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
What are 6 reasons when you should consider GCs?
- Acute flares and first time episodes
- Prior to starting IL-31 inhibitors
- Seasonal disease (3 mos or less)
- Other forms of therapy have failed
- Multimodal therapy
- Financial constraints
What are the 2 phases of GC therapy?
Reactive and Proactive
What does reactive therapy (phase 1) mean?
Induction of remission
What drugs would you use at point A?
Oral +/- topical GCs
What drugs would you use at point B?
Oclacitinib
What therapies would you use at A?
Allergen avoidance +/- immunotherapy
What drug would you use at B?
lokivetmab
What drug would you use at C?
cyclosporine
What drug would you use at D?
Oral +/- topical GCs
What drugs would you use at E?
Proactive topical GCs, Oclacitinib
What formulation of GC should be used in atopy?
Oral only
T/F: GCs should never be combined with other things
False; should be adjunctive with baths, fish oils, diet, etc.
What is the anti-inflammatory dose of steroids?
0.5-1 mg/kg/day PO (prednisone)
What is the minimum age and weight for cyclosporine use?
6 months, 4#
What is the basic MOA of cyclosporine?
It messes with IL-2 production from lymphocytes
What type of drug is cyclosporine?
Calcineurin inhibitor
What happens when IL-2 transcription is blocked?
Lymphocyte proliferation is suppressed and further production of relevant cytokines is inhibited
What are the 3 functions of a calcineurin inhibitor?
- Blocks IL-2 transcription
- Decreases APC #s and activation
- Decreases mast cell and eosinophil activation and production
What is the time to effect and overall efficacy of cyclosporine?
6 weeks and works in 4/5 dogs
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
How often should monitoring be done with cyclosporine?
every 6 months to 1 year
What are common adverse events of cyclosporine?
V/D, anorexia, gingival hyperplasia, hypertrichosis
What are 6 reasons to consider CsA?
- Patient >6 mos of age
- Smaller dogs (more cost effective)
- Condition is more inflammatory
- Otitis is major manifestation
- IL-31 inhibitors are ineffective or contraindicated
- Allergen specific immunotherapy has failed
What are the 2 IL-31 inhibitors?
Apoquel and Cytopoint
How many patients benefit from Apoquel?
60-70%
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
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
What other CKs does Apoquel suppress?
IL-2, 4, 6, 13
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
What is the #1 adverse event with Apoquel?
V/D and anorexia
What are 3 things which Apoquel might increase susceptibility to?
Bacterial infections, viral papillomas, demodicosis
What are additional side effects of Apoquel?
Lethargy and behavior change, increased thirst, weight loss or gain
What are 5 reasons when you should consider Apoquel?
- Patient is >1 yo
- Pruritus is main symptom or presentation
- Owners do not wish to pursue ASIT
- Recurrent pyoderma or Malassezia dermatitis
- Owner elects this form of therapy given options
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
What does it mean if a drug is USDA-labeled?
It is safe but doesn’t have to show efficacy
What type of drug is Cytopoint?
Lokivetmab (monoclonal Ab)
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)
What are the 4 unique aspects of mABs?
- Administered by injection
- Long half-lives
- Very targeted therapy with anrrower adverse event profiles
- Metabolized and excreted differently
How does cytopoint work?
- Ab binds and prevents binding of a protein to its receptor
- Ab has an agonist/antagonist effect on a membrane R
- Ab eliminates virus or malignant cell by C’ or cytotoxicity
What is nice about Cytopoint vs the other therapies (steroids, CsA, Apoquel)?
It has the least adverse effects
What is the duration of activity of Cytopoint?
4-8 weeks (usually 4)
What is the onset of action of Cytopoint?
<72 hr
What is the efficacy of Cytopoint?
7/10 dogs
What are the possible adverse effects of Cytopoint?
GI upset, lethargy, injection site discomfort
What are the major advantages to using Cytopoint?
Any age, any concurrent disease, any concurrent meds
When should Cytopoint be considered?
In any patient with atopy whose major symptom is pruritus, and in multimodal therapy
What does ASIT stand for?
allergen specific immunotherapy
ASIT is the most _____ long term management strategy.
economical
ASIT lacks long-term _____.
complications
ASIT is the best chance for a _____.
“cure”
What are the 5 indications for ASIT?
- Any atopic patient (early/first choice)
- Symptomatic therapy is not effective alone
- Patient can’t tolerate medical options
- Patient has conflicting concurrent medical conditions (chronic infections, DM)
- Owner chooses to address cause vs. symptoms
What are the multimodal components of the MOA of ASIT?
T cells, Ig class switching, CK expression
What is allergen selection for ASIT based on?
history and test results
The _____ of the reaction in ASIT does not necessarily correlate with the _____ of the allergen.
strength, significance
What are the 5 ASIT protocols?
Classic, Modified, Rush, Sublingual (SLIT), Intralymphatic
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
What is the modified ASIT protocol?
Starts with 20,000 PNU vial
What is the rush ASIT protocol?
Series of injections reaching maintenance in a day
What is the sublingual ASIT protocol?
3 vial series with increasing []
Given twice a day
When might we see improvement with the intralymphatic ASIT protocol?
By the 3rd injection
What is the main side effect of ASIT no matter what the route is?
Increased pruritus at the site of administration
What are other side effects of ASIT?
Swelling at injection site, urticaria/angiodema, anaphylaxis, V/D
What is the efficacy of ASIT?
60-70% of dogs demonstrate improvement
How long does it take for ASIT benefits to show?
6-12 months
What is RESPIT?
Regionally-specific immunotherapy available as an injectable or oral spray
